Volume: 5 • Issue: 3 & 4 • Septermber 2007

erg encies
a l Em
dic RPG & Acute Abdomen
e Explained
M

DIABETES
Know more to manage the menace

Monitoring Glycaemic Status

Gestational Diabetes
Diabetic Dyslipidemia

Insulins in Clinical Practice

Hypertension With Diabetes
 EDITOR SPEAKS

Vol. 5 Issue 3 & 4 April - Sept 2007

Consider these facts…..
Editor-in-Chief Dr. Vinay Aggarwal
Indians are more prone to
Sectional Editorial Dr. S. K. Wangnoo
developing diabetes than almost
Editorial Board
Dr. Ashok Grover
any other population in the
Dr. Hari Haran Dr. Sharda Jain world!
Dr. Parkash Gera Dr. S. Arul Rhaj India has the highest ever reported
Dr. Rajiv Gupta Dr. Deepak Pande
Dr. Atul Jain Dr. Yogesh Jhamb
number of 20 million people with
Dr. Vineet Jain Dr. Neeraj Jain diabetes, which has earned her
Dr. B.K. Gupta Mr. S.K. Singhal the dubious title of the “Diabetic Capital” of the World.
Mr. Atul Gandotra Dr. Madhumita Puri
And this is not all….
Photographer Mr. Mukesh Kapoor
Design and Layout Tabassum Indians tend to become diabetic at a relatively younger
age of 45 years, which is about 10 years earlier than
CONTENTS reported in the West. Further, a person’s life expectancy
1. Type 1 Diabetes - Presentation, 5 after developing diabetes is about 8 years after the onset
Diagnosis and Treatment of the disease, as they tend to succumb to kidney as well
2. Oral Medications to treat type 9 as heart disease more often than others.
2 Diabetes
3. Management of Post Prandial 11 There is a need for a concerted effort for all concerned
Hyperglycemia to learn of the pitfalls that lead to this disorder.
4. The Evolving Role of The Family 15 Precautionary measures would include measuring
Physician And Family Medicine the waist, and not just the body weight - to know the
5. Insulins in Clinical Practice – 17 progress of disease; and to avoid the paunch, not just
An Overview
obesity. Thus, physio-therapists and ‘weight-watchers’
5. Monitoring of Glycaemic status 21
alike require a better understanding of the causes of
6. Gestational Diabetes 25
7. Diabetic Dyslipidemia 29
diabetes and heart disease.
8. Treatment of Hypertension in 33 What is the profile of the potential diabetic? Modern
Adult Patients with diabetes - information allows for a reasonable ‘guess’: If a person
ADA Guidelines Review
is over 45 years of age, has a protruding and ‘big belly’
9. Rapidly Progressive 37
and has a family background of diabetes, it is almost
Glomerulonephritis
10. Approach to Acute Abdominal 43
certain that he or she will develop the disorder.
11. Maintaining Quality in Healthcare 49 Mere prescription of drugs and imposing restrictions on
Services diet is not the only answer for this problem. Instead,
12. Pushpanjali Family physicians 53 developing an acute understanding the disease in the
forum (PFPF)
local context and urging the acceptance of appropriate
13. Pushpanjali Health Care Events 54
and Initiatives
lifestyles are now urgently more than ever required.
14. Guidelines for Submission of 59 The present issue of “Medi-Focus” attempts to raise
Manuscripts these issues by covering a wide array of topics related
to diabetes and its complications. Brief reviews of
• Owned, Edited, Printed and Published by
Dr. Vinay Aggarwal for and on behalf of
the disease processes are given along with the latest
Pushpanjali Medical Publications Pvt. Ltd., recommendations in treatment. Topics pertaining
A-14, Pushpanjali, Vikas Marg Extn., to all the aspects of diabetes type 1 diabetes, type 2
Delhi-110092 diabetes, hypertension, lipids and gestational diabetes
• Printed at Kumar Offset Printer, 381, Patparganj
Industrial Area, Delhi - 110 092
are covered in this issue.
• All disputes to be settled in Delhi Courts only. I hope this will be helpful to physicians and internists
All rights reserved. alike and contribute to a better understanding of
• No responsibility is taken for returning
unsolicited manuscripts unless a self-addressed
diabetes.
stamped envelope is enclosed.
• Views expressed in articles in Pushpanjali
Medi-Focus do not necessarily reflect those of Dr. S. K. Wangnoo
the editorial board.

Vol. 5, Issue 3 & 4 April - Sept 2007

 EMPANELLED ORGANISATIONS
Cashless
(only after authorisation from co.)
1 Alankit Capsec. Pvt. Ltd.
2 BSES- except Genco & IPGCL
MEDICAL CENTRE 3 East West Assist.
H e a r t   &   Tr a u m a   H o s p i t a l 4 Family Health Plan Ltd
5 Genins India Pvt Ltd.
LIST of CONSULTANTS 6 Good Health Plan Ltd
CONSULTANT RESIDENCE CHAMBER MOBILE DAY/TIMING 7 Health India (BAISPL)-
MEDICAL DIRECTOR 8 Health India Pvt. Ltd
Dr. Vinay Aggarwal 22374612 22371818 9811050403 9 Heritage Health Services Pvt. Ltd.
MEDICAL SUPERINTENDENT
10 Heritagge Health Club
Dr. H. S. Nagi 95120-4125563 9818599722 9.00 am - 5.00 pm (Daily) 11 India Trade Promotion Ltd
12 MD India Pvt. Ltd
PHYSICIAN
13 Medi Assist Licensed TPA
Dr. Parkash Gera 22375440, 22371284 22075641 9810000944 11.30 am -1.00 pm (Daily)
14 Medicare Foundation Pvt. Ltd/
Dr. Sangeeta Bhargava 42440940, 22441900 22094921-22 9810249001 9.00 am - 10.00 am (Daily)
Focus Healthcare Pvt. Ltd.
PHYSICIAN & NON INASIVE CARDIOLOGIST 15 Medicare T.P.A. Services Pvt. Ltd
Dr. Mukesh Ajmera 22374502 9811008306 11.00 am - 1230 pm (Daily) 16 Medsave India Ltd.
PHYSICIAN-CHEST SPL. 17 Mother Dairy
Dr. Ashok Grover 22411236, 22541854 Fax. 22524700 9810121609 4.00 pm - 5.30 pm (Daily) 18 National Agricultural Cooperative
GYNAECOLOGIST Marketing Federation of India Ltd.
Dr. Sharda Jain 22238838-22238847 22414049-22453724 9312644808 8.00 am - 9.00 am (Daily) 19 Paramount Healthcare
Dr. Kanika Gupta 22149718, 22169718 9810183236 10.00 am - 12.00 noon Management Ltd.
(Tue, Wed, Fri) 20 Park Mediclaim Consultants
7.00pm-8.00 pm(Mon, Tue, Sat) Pvt. Ltd.
Dr. Bakul Arora 22750757, 22750551 9810089120 7.00 pm - 8.00 pm (Mon, Fri) 21 Pawan Hans Helicopters Ltd
Dr. Anita Jain 95120-4112881, 2640397 22582002 9810262229 1.00 pm - 2.00 pm (Daily) 22 Raksha TPA
Dr. Rekha Sarin 65261328 9818088114 9.00 am - 11.00 am 23 Safeway Mediclaim Services
(Mon, Thur, Sat) Pvt. Ltd
Dr. Sunita Lal 9810630691 5.00 pm - 6.00 pm (Mon.Thur)
24 TTK Healthcare Services Pvt. Ltd
SURGEON 25 United Healthcare Pvt. Ltd
Dr. Yogesh Jhamb 22378281 9811168281 11.30 am - 1.30 pm (Daily) 26 Universal Medi-Aid Services Ltd.
Dr. Yogesh Aggarwal 22238871 9810081484 6.00 pm - 8.00 pm (Daily) 27 Vipul Medcorp. Pvt. Ltd
Dr. Sameer Paruthi 9810061958 On Call
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CHILD SPECIALIST Communication
Dr. Deepak Pande 22243742, 42182025 22432218 9810366571 11.30 am - 1.00 pm (Daily) 29 Hygeia Care
Dr. Vineet Jain 95120-4112881, 2640397 22582002 9810121098 10.00 am - 12.00 noon (Daily)
Dr. Alok Gupta 65374625 9910227227 9312248808 5.00 pm - 6.30 pm (Daily) Reimbursement
PAEDIATRIC SURGEON 1 Arankari Placement Services
Dr. Anurag Krishna 24112687, 24114887 9810060565 1.00 pm - 2.00 pm (Sat) Pvt. Ltd.
ORTHOPAEDIC SURGEON 2 Bharat Heavy Electricals Ltd.
Dr. B.K.Malik 22778904 9811703004 6.00 pm - 8.00 pm (Daily) (BHEL) - Only for OPD (Only
Dr. Ashish Sao 9312010421 9.30 am - 12.30 pm doctors - Dr. Neeraj Jain,
(Mon, Wed, Fri) Dr. Atul Jain, Dr. Kanika Gupta,
Dr. Girish Chhabra 95120-2628200, 2625200 22507728 9810025926 9.30 am - 12.30 pm Dr. Ranjana Sharma, Dr. Ashok
(Tue, Thu, Sat) Grover, Dr.Yogesh Jhamb,
Dr. P.K.Dhar 22244801 9810038879 10.30 am - 12.00 noon (Daily) Dr. Girish Chabra & Dr. Parkash
Dr. Daulat Singh 22120442 22111872 9810244149 On Call Gera)
Dr. R.K.Sachdeva 22162135 22094892 9811073613 5.00 pm - 6.00 pm (Daily) 3 BSES Yamuna / Rajdhani / IPGCL
Dr. Alok Sharma 9312070380 6.00 pm - 8.00 pm (Daily) (Genco) Power Ltd.
ANAESTHETIST 4 Corporate Physicians
Dr. Rajesh Dhall 22167122 9810110405 On call (Tue, Thu, Fri, Sun) International *
Dr. Swaraj Garg 22543003 22548796, 22519888 9811441064 On call (Mon, Wed) 5 Dabur & Excelcia Foods
Dr. Rakesh Atray 22152245, 22157745 9810272563 On call (Sat) 6 Gopal Industries Pvt. Ltd.
ENT SURGEON 7 Hospital Services Consultancy
Dr. Atul Jain 22376205 22545000 9811120545 12.00 noon - 1.30 pm (Daily) Corporation (India) Ltd.
Dr. Anurag Jain 22720901 9810249015 8.30 pm - 9.30 pm (Daily) 8 M/s Venus Medicare Services.
Dr. Vyomesh Bansal 9310071990 6.00 pm - 8.00 pm 9 Maruti Udyog Ltd.
(Tue, Thu, Sat) 10 Medicare Service Club
GASTROENTEROLOGIST 11 Micromatic Machine Tools
Dr. Neeraj Jain 22371024 22545000 9810166989 4.00 pm - 6.00 pm (Daily) Pvt. Ltd. - Only for OPD
12 MetLife India Insurance
ONCOLOGIST
Co. Pvt. Ltd. - Only for OPD
Dr. Sudersan De 26252065 9810227340 On call (Tue), by appointment
13 National Building Construction
ONCO SURGEON Corporation Ltd.(NBCC)
Dr. Praveen Jain 22146173 22149256 9810139314 On call 14 National Industrial Development
Dr. Umang Mittal 95121-2668149 9412201474 4.00 pm - 6.00 pm (Wed) Corporation Ltd.
11.00 am- 12.00 noon (Sat) 15 National Projects Construction
EYE SPECIALIST Corporation Ltd.
Dr. L.D. Sota 26016636 9312876694 10.00am-1.00pm Daily 16 National Textile Corporation
(except Wed) (NTC)
4.00pm-7.00pm (Wed) 17 Central Electrical Ltd. ( CEL)
Dr. P. C. Bhatia 26515263, 26863998 9810064554 On call


Vol. 5, Issue 3 & 4 April - Sept 2007
 CONSULTANT RESIDENCE CHAMBER MOBILE DAY/TIMING
URO-SURGEON
Dr. C.M.Goel 95120 2630717 95120 2630365 9811047047 1.00 pm - 2.00 pm (Mon, Thu)
PATHOLOGIST
Dr. Vandana Arora 22246806 9811009938 9.00 am - 4.00 pm (Daily)
Dr. Archana Sood 22096401 9312319887 On Call
MICROBIOLOGIST
Dr. Narinder Saini 22376289 22381445 9810252127 8.00 am - 9.00 am (Daily)
RADIOLOGIST
Dr. Mukesh Koshal 22546704 9810062179 12.00noon - 1.30 pm (Daily)
NEUROLOGIST
Dr. B.K.Gupta 22371675, 22371033 30946399 9811084263 On Call
Dr. Nirmala Lahoti 22540271, 22526601 9810061981 On Call
Dr. Aditya 9810556353 9.00 am - 11.00 am
(Tue, Thur, Sat)
NEURO SURGEON
Dr. J. Kumar 9810273684 On Call
Dr. Vikas Gupta 9810661522 7.00 - 8.00 pm (Tue, Fri) List of Consultants
NEPHROLOGIST CONSULTANT DAY / TIMINGS
Dr. Neeru Aggarwal 95120-2724591 95120-2780736 9810266275 1.00 pm - 2.00 pm (Mon to Fri)
PHONE NO
9.00 am to 10.00 am (Sat)
PSYCHIATRIST PHYSICIAN
Dr. Raman Jeet Jaswal 22526533 9810526533 On call Dr. Ruby Bansal 9.00 am - 11.00 am
Dr. Vikas Mohan Sharma 22623183 9810412911 6.00 - 8.00 pm (Fri) R) 2614076 (Daily)
M) 9891376756
PSYCHOSEXUAL DISORDERS
Dr. (Col.) V.K. Wadia 55469686 26140058 9891192777 6.00 pm - 8.00 pm (Fri)
CHILD SPECIALIST
PSYCHOLOGIST
Dr. (Mrs.) VT Boppal 9.00 pm - 10.00 am
Dr. Deepali Batra 9818425297 4.00 pm - 6.00 pm (Wed, Fri)
M) 9811161590 (Daily)
CARDIOLOGIST
Dr. Lokesh Chandra Gupta 9310124059 9810124059 7.00 pm- 9.00 pm SURGEON
(Mon, Wed, Fri)
Dr. Vijay S. Pandey 11.00 am - 1.00 pm
ENDOCRINOLOGIST R) 95120-2628254 (Mon, Thur)
Dr. S.K.Wangnoo 22618242, 22621357 95120-2921446 9810113922 On Call M) 9818492809
DENTIST
Dr. Geeta Paul 9811415489 9810292498 10.00 am - 2.00 pm (Daily) ENDOCRINOLOGIST
5.00 pm -8.00 pm Dr. S.K. Wangnoo 7.00 pm - 9.00 pm
PHYSIOTHERAPIST R) 22618242 (Mon, Wed)
Dr. Md. Majid Khan 9873207660 9.00 am - 1.00 pm (Daily) 22621357
HOMOEOPATHIC PHYSICIAN M) 9810113922
Dr. M.M. Aggarwal 22434770 22094879 22513835
DENTAL SURGEON
PLASTIC SURGEON
Dr. R.K. Sandhir 95120-2458588 22592073, 22169732 9810033525 On Call Dr. Jyoti Goyal 10.00 am - 1.30 pm
Dr. Manoj Bansal 22155057 22097417, 22093107 9810003628 11.00 am - 1.00 pm (Daily) R) 986878041 6.00 pm - 9.00 pm
Dr. Gopal Goyal (Daily)
SKIN SPECIALIST
M) 9868235811
Dr. V.K. Upadhyaya 22152084 22091758 9810033882 On call
Dr. Mukesh Girdhar 95120-2625544 22372484 9810078198 On call
Dr. Ritu Gupta 9891063467 10.00 am -11.00 am DERMATOLOGIST
(Mon to Fri) Dr. Ritu Gupta 7.30 pm - 9.00 pm
Dr. Ritika Gupta 9818560759 On call R) 22371114 (Wed, Fri)
CHEST SURGEON M) 9891063467
Dr. R.C. Jain 26803436, 26808035 9811106203 On call
ENT
RHEUMATOLOGIST
Dr. Saket Aggarwal 11.00 am - 1.00 pm
Dr. Anish Aggarwal 95120-2753546 9810073795 4.00 pm - 7.00 pm (Fri)
M) 9811231599 (Mon, Thurs)
Others
Dr. Poonam Gupta 22095708 22161397 9811744426 PHYSIOTHERAPIST
Dr. S.P. Singh 22152036 9811152254
Dr. Md. Majid Khan 1.00 pm - 4.00 pm
Dr.Jyoti Aggarwal 22238871 9910081484
M) 9873207660 (Daily)
Dr. Deepak Lahoti 9810123067
Dr. Madhu Ahuja 22516733 22541842 9810067539
Dr. Sonika Saraswat 8.00 am - 3.00 pm
FAMILY PHYSICIANS
M) 9899649920 (Daily)
Dr. V.K.Malhotra 22157127 9313100602 On Call
Dr. Ajay Aggarwal (B/o MD) 9810130292 On Call
Dr. Ajay Arora 22156672 22510904 9810049714 On Call Dr. Sachin Kr. Gupta 4.00 am - 8.00 pm
Dr. Vipin Jain 22372065 22412008 9811047912 On Call M) 9873322564 (Daily)
Dr. K.B. Bhatia 22372727 22372728 9811319070 On Call
Dr. Hari Haran 22549804 22540624 9810197049 On Call HOMOEOPATHIC
Dr. Atul Aggarwal 22459608 9811137098 Dr. Deepak Karla 11.00 am - 1.00 pm
Dr. D.R. Rai 9312504480 M) 9313882040 (Thur, Sat)
Dr. V.P. S. Chawla 9811305435
Dr. Sangeeta Gupta 9810395657
Dr. Ashwani Goyal 22112343 9811112688
Dr. A.K. Jain 9871803070
Dr. Rakesh Gupta 22155979, 55298198


Vol. 5, Issue 3 & 4 April - Sept 2007

Archana D. Arya
Consultant Pediatric
Endocrinologist
Centre for Child Health,
Sir Ganga Ram Hospital
New Delhi
Vol. 5, Issue 3 & 4 April - Sept 2007
Type 1 Diabetes - Presentation,
Diagnosis and Treatment
Type 1 Diabetes, also known as “Insulin
Dependent Diabetes Mellitus” or “Juvenile
Diabetes” in the past, accounts for two thirds of
children with diabetesa.
Presentation
B cell destruction due to an autoimmune
process results in insulin deficiency in type 1
diabetes, which is responsible for the classical
symptoms of polyuria, polydipsia and weight
loss. Polyuria may present as bed wetting in a
previously toilet trained child. Polyphagia is not
present often since ketosis leads to anorexia in
these children.
Sometimes these classical symptoms may
go unnoticed and the child may present
with symptoms of ketoacidosis (DKA) such
as pain abdomen and vomiting, and may be
misdiagnosed as gastroenteritis. Associated
symptoms that may be present in diabetic
children are pyogenic skin infections, monilial
vaginitis and dysuria in young girls. These are
usually associated with polyuria and polydipsia
and are rarely isolated symptoms of type 1
diabetes. Dehydration with very wet diapers/
persistent monilial infection in the diaper area
in babies should arouse suspicion of diabetes.
Rarely transient hyperglycemia may occur in
children during stressful situations such as
severe illnesses or high dose glucocorticoid
therapy. In these instances hyperglycemia is
not severe, going to a maximum of 300 to 400
mg/dl.
Diagnosis
Fasting blood glucose of more than 126 mg/dl
and a random blood glucose of 200 mg/dl or
more is diagnostic of diabetes.
v In a lean child below 10 years of age with
high blood glucose levels and ketosis with
or without acidosis and no family history of
diabetes, the most likely diagnosis is type 1
diabetes.
v In children who are obese with signs of
insulin resistance such as acanthosis
nigricans, and especially with a family
history of type 2 diabetes, the possibility of
type 2 diabetes must be kept in mind, even
if they present with ketosis and tests must
be undertaken to distinguish between type
1 and type 2 diabetes.
Management of Type 1 Diabetes
A sick dehydrated child with DKA must be
admitted for correction of fluid and electrolyte

Archana D. Arya
imbalances as well as intravenous insulin
therapy. If the child is metabolically stable at
the time of diagnoses, and if facility of a good
diabetes education team is available to educate
the parents, and help them with management,
treatment can be initiated on an outpatient
basis.
If these facilities are not available it is advisable
to admit the child for initiation of insulin
therapy and for the purpose of providing
diabetes education to the family. Duration of
admission should be as short as possible since
better control of hyperglycemia is achieved once
the child is performing routine activities.
Insulin Therapy
Insulin Preparations
There are various insulin preparations available
in the market. Human insulin has replaced
porcine insulin in most parts of the world,
although studies suggest that they cause
asymptomatic hypoglycemia more often than
the porcine preparations. Fast acting regular
insulin, ultra fast acting insulin analogs such
as lispro and detemir, intermediate acting NPH
insulin and peakless basal insulin analogs
such as aspart and glargine can be used for
management. Recently, inhaled insulin has
become clinically available in USA. It has not
been approved by the FDA for use in children
less than 18 years of age.
Insulin Regimens
Younger children can be managed with a split
dose regimen of regular or rapid acting with
NPH insulin injected before breakfast and
dinner. In older children, it is preferable to use a
combination of basal insulin to provide 24-hour
insulin coverage and regular or rapid acting
insulin to cover the post meal glucose peak.
Premixed insulin preparations are usually not
preferred because of the inability to adjust doses
according to meal plans. They may be used in
patients with compliance problems. Continuous
subcutaneous insulin infusion (CSII) by means
of insulin pump may be used for management.
It results in improved control of hyperglycemia
and more flexibility of lifestyle. Cost of therapy
is a major factor limiting its use in our country.
Insulin Dosage
Initial requirement of insulin may be up to
1u/kg/day. About 65% patients will undergo
partial remission (honeymoon period) a few
weeks following diagnosis due to residual B cell function, when
the insulin requirement may be <0.5u/kg/day. The duration of
this phase varies in different patients and once the residual B cell
function is lost, most preadolescents will need about 0.8u/kg/d
and adolescents would need 1.0u/kg/d of insulin. During puberty
the insulin requirement may increase up to 1.5-1.8u/kg/d due to
the insulin resistance caused by the hormonal milieu.
Medical Nutrition Therapy
This is an integral part of diabetes management. A balance
between nutrition and exercise is as important for good control
as adjusting insulin doses, but is often neglected. Nutritionist
consultation regarding diet is a very important part of managing
type 1 diabetes. About 50-55% of the caloric intake should be
from carbohydrates, 30% from fats and about 15-20% from
proteins. Diet should be individualized according to the child’s
activities and metabolic needs. Children on CSII and basal
insulin follow carbohydrate counting to decide the insulin dose
at some centers.
Exercise
Diabetic children should be encouraged to exercise for
30-60 minutes at-least 5 times a week. Snack should be provided
and insulin dose adjusted, based on the time and duration of
exercise.
Goals of Therapy
The goal of therapy is to provide metabolic normality and physical
and emotional health to the patient. This can be provided by:
v Elimination of diabetic symptoms such as polyuria,
polydipsia
v Prevention of acute complications like hypoglycemia and
DKA
v Ensuring normal growth and sexual maturation
v Early detection of associated diseases
v Prevention of hyperlipidemia
v Counseling for emotional disorders
v Prevention of chronic vascular complications
Good glycemic control is of prime importance for achieving
the above objectives and this can only be achieved by frequent,
regular monitoring. The Diabetes Control and Complications
Trial (DCCT) has shown that there is a marked reduction in
diabetes-associated complications with frequent monitoring and
multiple insulin injections, but is associated with a high risk of
hypoglycemia. Hence intensive therapy is not recommended for
very young children.
Goals of therapy in the management of type 1 diabetes should
be individualized according to the age and socioeconomic
background of the patient. For optimal control it is recommended
that the blood glucose (BG) level remains in the range 5. Diabetes Control and Complications Trial Research
80-120 mg/dl in fasting state and 80-140 mg/dl before meals.
In toddlers and young children who have hypoglycemic
unawareness the goals should not be as rigid. It is recommended
that they maintain their fasting BG within 100-140 mg/dl and a
BG of 100-180 mg/dl before meals.
Monitoring
A glucometer should be used for monitoring BG at home. If it
is not affordable, a dextrostix can be used. The strips can be
divided longitudinally and can be used twice. Urine glucose for
monitoring is not a good substitute for BG measurement, since it
cannot detect hypoglycemia. If it is practiced, the patient should
double void before testing.

Vol. 5, Issue 3 & 4 April - Sept 2007
Another BG monitoring system known as the continuous
glucose monitoring system (CGMS) is now available in India.
CGMS continuously measures subcutaneous tissue interstitial
glucose levels, recording average values every 5 minutes within
a range of 40400 mg/dl. Glucose values obtained with the CGMS
have been shown to correlate with laboratory and glucometer
measurements of BG. CGMS provides an alarm to warn if the BG
is too high or low.
Blood Glucose should be monitored daily, before each meal and
periodically at bedtime and 2-3 am, depending on the insulin
regimen. In addition, it should be checked if hypoglycemia is
suspected and frequently during illness. BG readings should be
recorded and the dose of insulin should be modified based on
the reading.
Urine ketones must be checked if BG is greater than 30 0mg/dl,
during illness and in the fasting state if possible
Follow Up
The patient should visit the doctor every 3-4 months. Height and
weight should be measured at every visit and pubertal status
assessed adolescents. Complete physical examination including
thyroid gland examination and inspection of injection sites for
hypertrophy should be done. Blood glucose records should be
scrutinized and appropriate changes in the insulin dose should
be made.
Glycosylated Hb (HbA1C ) should be checked every 3-4 months.
It should remain below 8% at all times. Goals can be specific for
each individual.
Lipid profile, 24-hour or a timed collection of urine for
microalbumin and eye examination should be performed
annually. Routine surveillance for associated autoimmune
disorders should be done as far as possible.
Suggested Reading:
1. Springer D, Dziura J, Tamborlane WV, Steffen AT, Ahern JH,
Vincent M Weinzimer SA. Optimal control of type 1 diabetes
mellitus in youth receiving intensive treatment. J Pediatr.
2006 Aug;149(2):154-6.
2. Daneman D. Type 1 diabetes mellitus. Lancet. 2006
Mar 11; 367 (9513) : 847-58.
3. Haller MJ, Atkinson MA, Schatz D. Type 1 diabetes mellitus:
etiology, presentation, and management. Pediatr Clin North
Am. 2005 Dec; 52 (6) : 1553-78.
4. Daneman D, Wolfson DH, Becker DJ, Drash AL : Factors
affecting glycosylated hemoglobin values in children with
insulin-dependent diabetes. J Pediatr 99 : 847853, 1981
Group: The effect of intensive treatment of diabetes on the
development and progression of long term complications
in insulin-dependent diabetes mellitus. N Engl J Med
329 : 977986, 1993
6. Mecklenburg R, Benson J, Becker N, Brazel P, Fredlund P,
Metz R, Nielson R, Sanner C, Steenrod W: Clinical use of the
insulin infusion pump in 100 patients with type 1 diabetes.
N Engl J Med 307 : 513518, 1982.
7. Davies AG, Baun JD : A decade of insulin infusion pumps.
Arch Dis Child 63 : 329332, 1988
8. Tsui E, Barnie A, Ross S, Parkes R, Zinman B: Intensive insulin
therapy with insulin lispro : a randomized trial of continuous
subcutaneous insulin infusion versus multiple daily insulin
injections. Diabetes Care 10 : 17221727, 2001

S.K. Wangnoo
Senior Consultant
Endocrinologist
Apollo Centre for Obesity
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Garima S Gupta
Registrar
Apollo Centre for Obesity
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Vol. 5, Issue 3 & 4 April - Sept 2007
Oral Medications to Treat Type 2 Diabetes
The epidemic of type 2 diabetes in the latter
part of the 20th and in the early 21st century,
and the recognition that achieving specific
glycemic goals can substantially reduce
morbidity, has made the effective treatment
of hyperglycemia a top priority. Maintaining
glycemic levels as close to the non-diabetic
range as possible has been demonstrated to
have a powerful beneficial impact on diabetes-
specific complications, including retinopathy,
nephropathy, and neuropathy in the setting
of type 1 diabetes; in type 2 diabetes, more
intensive treatment strategies have likewise
been demonstrated to reduce complications.
The development of new classes of blood
glucose-lowering medications to supplement
the older therapies, such as lifestyle-directed
interventions, insulin, sulfonylureas, and
metformin, has increased the treatment options
for type 2 diabetes. Whether used alone or in
combination with other blood glucose-lowering
interventions, the availability of the newer
agents has provided an increased number
of choices for practitioners and patients and
heightened uncertainty regarding the most
appropriate means of treating this widespread
disease. Although numerous reviews on the
management of type 2 diabetes have been
published in recent years, practitioners are
often left without a clear pathway of therapy
to follow.
Clinical trials, such as the Diabetes Control and
Complications Trial (DCCT), the Stockholm
Diabetes Intervention Study (SDIS) in type
1 diabetes and the UK Prospective Diabetes
Study (UKPDS) and Kumamoto Study in type
2 diabetes, have helped establish the glycemic
goals of therapy that result in improved long-
term outcomes.
The most recent glycemic goal recommended
by the American Diabetes Association, selected
on the basis of practicality and the projected
reduction in complications over time, is “in
general” an A1C level <7%. For “the individual
patient,” the A1C should be “as close to
normal (<6%) as possible without significant
hypoglycemia.” The most recent glycemic
goal set by the European Union International
Diabetes Federation is an A1C level <6.5%.
Factors such as life expectancy and risk for
hypoglycemia need to be considered for
every patient before intensifying therapeutic
regimens.
Choosing specific antihyperglycemic agents is always a matter of concern because of
is predicated on their effectiveness in its potentially fatal outcome. Metformin

S.K. Wangnoo1 and Garima S Gupta2
lowering glucose, extraglycemic effects that
may reduce long-term complications, safety
profiles, tolerability, and expense.
Effectiveness in Lowering Glycemia
Apart from their differential effects on
glycemia, there are insufficient data at this
time to support a recommendation of one class
of glucose-lowering agents, or one combination
of medications over others with regard
to effects on complications. However, the
different classes do have variable effectiveness
in decreasing glycemic levels, and the
overarching principle in selecting a particular
intervention will be its ability to achieve and
maintain glycemic goals.
A major factor in selecting a class of drugs, or
a specific medication within a class, to initiate
therapy or when changing therapy, is the
ambient level of glycemic control. When levels
of glycemia are high (eg, A1C >8.5%), classes
with greater and more rapid glucose-lowering
effectiveness, or potentially earlier initiation
of combination therapy, are recommended;
conversely, when glycemic levels are closer to
the target levels (e.g., A1C <7.5%), medications
with lesser potential to lower glycemia and/or
a slower onset of action may be considered.
Obviously, the choice of glycemic goals and
the medications used to achieve them must
be individualized for each patient, balancing
the potential for lowering A1C and anticipated
long-term benefit with specific safety issues,
as well as other characteristics of regimens,
including side effects, tolerability, patient
burden and long-term adherence, expense, and
the nonglycemic effects of the medications.
Finally, type 2 diabetes is a progressive disease
with worsening glycemia over time. Therefore,
addition of medications is the rule, not the
exception, if treatment goals are to be met over
time.
Metformin
Metformin is the only biguanide available
in most parts of the world. Its major effect
is to decrease hepatic glucose output and
lower fasting glycemia. Typically, metformin
monotherapy will lower A1C by ~1.5
percentage points. It is generally well tolerated,
with the most common adverse effects being
gastrointestinal. Lactic acidosis though quite
rare (<1 case per 100,000 treated patients),
monotherapy is usually not accompanied by hypoglycemia and
has been used safely, without causing hypoglycemia, in patients
with pre-diabetic hyperglycemia. The major nonglycemic
effect of metformin is either weight stability or modest weight
loss, in contrast to many of the other blood glucose-lowering
medications.
Sulfonylureas
Sulfonylureas lower glycemia by enhancing insulin secretion
and A1C by ~1.5 percentage points. The major adverse side
effect is hypoglycemia, but severe episodes, characterized by
need for assistance, coma, or seizure, are infrequent. However,
such episodes are more frequent in the elderly. Episodes can
be both prolonged and life threatening, although these are very
rare. Several of the newer sulfonylureas have a relatively lower
risk for hypoglycemia. In addition, weight gain of ~ 2 kg is
common with the initiation of sulfonylurea therapy.
Glinides
Like the sulfonylureas, the glinides stimulate insulin secretion,
although they bind to a different site within the sulfonylurea
receptor. They have a shorter circulating half-life than the
sulfonylureas and must be administered more frequently. Of
the two glinides currently available, repaglinide is almost as
effective as metformin or the sulfonylureas, decreasing A1C by
~1.5 percentage points. Nateglinide is somewhat less effective
in lowering A1C than repaglinide when used as monotherapy
or in combination therapy. The glinides have a similar risk
for weight gain as the sulfonylureas, but hypoglycemia may
be less frequent, at least with nateglinide, than with some
sulfonylureas.
a Glucosidase Inhibitors
a-Glucosidase inhibitors reduce the rate of digestion of
polysaccharides in the proximal small intestine, primarily
lowering postprandial glucose levels without causing
hypoglycemia. They are less effective in lowering glycemia
than metformin or the sulfonylureas, reducing A1C by 0.5-
0.8 percentage points. Since carbohydrate is absorbed more
distally, malabsorption and weight loss do not occur; however,
increased delivery of carbohydrate to the colon commonly
results in increased gas production and gastrointestinal
symptoms. This is the most common cause of discontinuation
of these classes of drugs.
Thiazolidinediones
Thiazolidinediones (TZDs or glitazones) are peroxisome
proliferatoractivated receptor ã modulators; they increase the
sensitivity of muscle, fat, and liver to endogenous and exogenous
insulin (“insulin sensitizers”). The limited data regarding the
blood glucose-lowering effectiveness of TZDs when used as
monotherapy have demonstrated a 0.5-1.4% decrease in A1C.
The most common adverse effects with TZDs are weight gain
and fluid retention. There is an increase in adiposity, largely
subcutaneous, with redistribution of fat from visceral deposits
shown in some studies. The fluid retention usually manifests
as peripheral edema, though new or worsened heart failure
can occur. The TZDs either have a beneficial or neutral effect
on atherogenic lipid profiles, with pioglitazone having a more
beneficial effect than rosiglitazone.
Recent controversies surrounding the use of rosiglitazones and
an increased risk of adverse cardiac events have fuelled anxiety
10
Vol. 5, Issue 3 & 4 April - Sept 2007
in the minds of practitioners about their use in diabetics.
However, data at this point of time is insufficient to add to this
controversy and while prescribing these medications, the risk
to benefit ratio should be carefully weighed.
Incretin and Incretin Mimetics
Incretins are hormones released from the gastrointestinal
tract in response to nutrient ingestion that potentiate glucose-
stimulated insulin secretion from islet beta cells. The
search for incretins was prompted by the observation that
administration of an oral glucose load leads to a much greater
stimulation of insulin release than a comparable glucose
load given intravenously. This connection between the gut
and the pancreatic islets is known as the enteroinsular axis
and is deemed responsible for ~50% of postprandial insulin
release. The 2 predominant incretins are glucagon-like peptide
(GLP)-1 and glucose-dependent insulinotropic peptide (GIP).
These 2 peptides stimulate insulin secretion, and, unlike
other insulinotropic agents, they do so in a glucose-dependent
manner. In light of these beneficial actions, GLP-1 and GIP
represent potential therapeutic agents for the treatment of type
2 diabetes. However, because exogenous GIP is comparatively
less effective than GLP-1 in stimulating insulin secretion in
type 2 diabetics, while the insulinotropic action of GLP-1 is
well preserved; much of the current research has focused on
enhancing GLP-1 action for the treatment of type 2 diabetes.
GLP-1 also exerts a number of other biological actions that
contribute to its ability to lower glucose, including inhibition
of gastric emptying, which reduces meal-associated increases
in glycemic excursion. GLP-1 also inhibits glucagon secretion
and suppresses food intake in both diabetic and nondiabetics.
Furthermore, GLP-1 has the potential to preserve or enhance
beta-cell function in subjects with type 2 diabetes due to its
ability to stimulate beta-cell proliferation and neogenesis and
inhibit apoptosis.
However, the major therapeutic drawback to using native GLP-
1 is its very short half-life of less than 2 minutes following
exogenous administration, due in part to the protease dipeptidyl
peptidase (DPP)-IV. As a result, preventing the degradation of
native GLP-1 by inhibiting the activity of the DPP-IV enzyme
has emerged as a therapeutic strategy for enhancing endogenous
GLP-1 action in vivo.
DPP IV Inhibitors
The apparent beneficial effects on beta-cell function raise
the possibility that these agents may be able to modify the
natural history of type 2 diabetes. Although the emerging safety
profile of the DPP-IV inhibitors appears to be excellent, the
long-term safety of these agents has not yet been ascertained.
Similarly, although DPP-IV inhibitors exhibit promising short-
term effects on enhancement of beta-cell function, their long-
term durability compared with other oral antidiabetic agents
used in the treatment of type 2 diabetes remains unknown.
In addition, whether any meaningful differences will emerge
among the different chemical classes of DPP-IV inhibitors
currently under development cannot as yet be determined.
Taken together, the latest available clinical data support the
considerable early promise associated with the sustained
enhancement of incretin action, making it increasingly likely
that DPP-IV inhibitors may prove to be useful for the treatment
of type 2 diabetes. Currently, the DPP-IV inhibitors under
various phases of research and marketing are Sitagliptin,
Saxigliptin and Vildagliptin.

S.K. Wangnoo
Senior Consultant
Endocrinologist
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New
Delhi
Vol. 5, Issue 3 & 4 April - Sept 2007
Management of Post Prandial
Hyperglycemia
Type 2 diabetes is a serious condition that is
associated with a number of life-threatening
complications, including coronary disease.
In addition to being a marker for the onset
of type 2 diabetes, post-prandial glycemia
(PPG) appears to be associated with the
development of both the macro vascular and
micro vascular complications of diabetes,
independently of HbA1c and FPG levels.
Numerous epidemiological studies have
shown elevated postprandial/post-challenge
glucose to be independent and significant
risk factors for macro vascular complications
and increased mortality risk. There is much
evidence to suggest that elevated plasma
glucose levels contribute to the development
of atherosclerotic lesions. Many studies
have shown that there is a strong correlation
between elevated plasma glucose levels and
the risk of developing cardiovascular disease.
Large, randomized, prospective trials have
demonstrated that reductions in hyperglycemia
and management of diabetes-related risk
factors significantly reduce micro vascular
and macro vascular complications in patients
Table:
Epidemiological studies showing an association between post-prandial hyperglycemia with risk
of CVD and mortality
Hoorn Study 2-h glucose better predictor of mortality than
Honolulu Heart
Chicago Heart Study
DECODE
Coutinho et al
Whitehall Study, Paris Prospective Study,
and Helsinki Policemen Study
Diabetes
Role of Post-Prandial Hyperglycemia
Recent studies demonstrate that hyperglycemia
induces an overproduction of superoxide by
the mitochondrial electron-transport chain.
Superoxide overproduction is accompanied
by increased Nitric Oxide (NO) generation,
due to endothelial NO synthase (eNOS) and
inducible NO synthase (iNOS) uncoupled state,
11
S. K. Wangnoo
with either type 1 or type 2 diabetes. Findings
from the Diabetes Control and Complications
Trial (DCCT), the Kumamoto study, and the
United Kingdom Prospective Diabetes Study
(UKPDS), which demonstrated that therapies
directed at achieving normal glycemia reduce
the development and delay the progression of
long-term micro vascular complications. These
trials demonstrated a 30-35% reduction in
micro vascular complications per 1% absolute
reduction of glycosylated hemoglobin (HbA1c).
Furthermore, epidemiological data from the
UKPDS also showed a 14-16% decrease in macro
vascular complications for every 1% absolute
reduction in glycosylated hemoglobin-with no
glycemic threshold for a substantive change in
the risk for any of the clinical outcomes studied.
In other words, risk reduction extended into the
normal range for HbA1c. To achieve maximum
benefit from treatment, many researchers and
clinicians now believe that HbA1c values must
be kept close to 6.5% (International Diabetes
Federation, IDF and American College of
Endocrinology, ACE), which is slightly above the
normal range in nondiabetic patients (<6%).
HbA1c
1-h glucose predicts Program coronary heart
disease
2-h post challenge glucose predicts all-cause
mortality
High 2-h post load blood glucose is associated
with increased risk of death, independent of
fasting glucose
2-h glucose associated with CHD
2-h post challenge glucose predicts all-cause
and CHD mortality
Post meal but not fasting glucose is associated
with CHD, coronary heart disease.
a phenomenon favoring the formation of the
strong oxidant peroxynitrite, which in turn
damages DNA. DNA damage is an obligatory
stimulus for the activation of the nuclear enzyme
poly (ADP-ribose) polymerase. Poly (ADP-
ribose) polymerase activation in turn depletes
the intracellular concentration of its substrate
NAD+, slowing the rate of glycolysis, electron
transport, and ATP formation and produces an
ADP ribosylation of the GAPDH (glyceraldehyde-3-phosphate
dehydrogenase).
Several indirect and direct evidences support the concept
that acute hyperglycemia works through the production of an
oxidative and nitrosative stress. Indirect evidence is obtained
through the use of antioxidants. The fact that antioxidants can
hinder some of the effects acutely induced by hyperglycemia,
such as endothelial dysfunction, activation of coagulation, and
plasmatic increase of ICAM-1 and interleukins, suggests that the
action of acute hyperglycemia is mediated by the production of
free radicals.
Direct evidence is linked to the estimate of the effects of acute
hyperglycemia on oxidative stress markers. It has been reported
that during oral glucose challenge, a reduction of the antioxidant
defenses is observed. The role of hyperglycemia is highlighted
by the fact that giving two different meals, which will result into
two different levels of postprandial hyperglycemia, the greater
drop in the antioxidant activity is linked with the higher levels
of hyperglycemia. The evidence that in diabetic subjects, LDLs
are more prone to oxidation in the postprandial phase matches
these data. Even in this situation, higher levels of hyperglycemia
are matched with a greater oxidation of LDLs. Interesting and
new data are available on the possible generation of nitrosative
stress during postprandial hyperglycemia. The simultaneous
overgeneration of NO and superoxide favors the production of a
toxic reaction product, the peroxynitrite anion. The peroxynitrite
anion is cytotoxic because it oxidizes sulfydryl groups in proteins,
initiates lipid peroxidation, and nitrates amino acids such as
tyrosine, which affects many signal transduction pathways. The
production of peroxynitrite can be indirectly inferred by the
presence of nitrotyrosine, and it has recently been reported that
nitrotyrosine is an independent predictor of CVD.
However, dyslipidemia also is a recognized risk factor for CVD
in diabetes, and postprandial hyperlipidemia contributes to
this risk. In non obese type 2 diabetic patients with moderate
12
Vol. 5, Issue 3 & 4 April - Sept 2007
fasting hypertriglyceridemia, the atherogenic lipoprotein profile
is amplified in the postprandial state. Such observations have
raised the question of whether postprandial hyperlipidemia,
which rises concomitantly with postprandial hyperglycemia, is
the true risk factor. However, evidence suggests that postprandial
hypertriglyceridemia and hyperglycemia independently induce
endothelial dysfunction through oxidative stress. It is now
well recognized that endothelial dysfunction is one of the first
stages, and one of the earliest markers, in the development of
CVD. Endothelial function is altered early in diabetes. It has
been demonstrated that in diabetic subjects, the vasodilating
response to stimuli is diminished and that this anomaly is
related to glycemic control. This effect of hyperglycemia is
probably linked with a reduced production/bioavailability of
NO, since hyperglycemia-induced endothelial dysfunction is
counterbalanced by arginine. Furthermore, it is very interesting
that a rapid decrease of flow-mediated vasodilation has been
shown in the postprandial phase in type 2 diabetic patients and
that the decrease correlated inversely with the magnitude of
postprandial hyperglyemia.
The possible role of hyperglycemia in the activation of blood
coagulation indicates that acute glycemic variations are matched
with a series of alterations of coagulation that are likely to cause
a thrombosis.
Management Options
Diet and Exercise
Dietary counseling, regular physical exercise, and weight loss
have been recommended for all patients with diabetes. The
total amount and nature (composition, portion size, preparation
method, consumption, and digestion rate) of the carbohydrates
consumed are all important determinants of PPG levels, and low
carbohydrate/low glycemic index diets can blunt PPHG, at least
in the short-term.
Medications postprandial glucose excursions and HbA1c values. The GLP-1
analogue exenatide, which has a longer duration of action than
Strategy Therapy that of naturally occurring GLP-1, reduces FPG and PPG values,
Delay appearance of glucose Low GI foods, Glucosidase decreases appetite, and delays gastric emptying. The DPP-IV
inhibitors, GLP, Amylin inhibitor sitagliptin delays the degradation of endogenous GLP-
1, lowers HbA1c values, and helps improve glycemic control.
Increase early PP insulin Insulin analogue, Inhaled
level insulin
Conclusion
Improve meal related insulin Glucose Potentiators -
Evidence accumulates suggesting that postprandial excursions
secretion Replaglinide, GLP-1
of blood glucose may be involved in the development of diabetes
Inhibit glucagons Glucagon antagonists, GLP complications, particularly (but not only) cardiovascular
Inhibit PP gluconeogenesis -1 Metformin complications.
Improve insulin action Insulin Sensitizers However, many questions remain unanswered regarding the
definition of postprandial glucose and, perhaps most importantly,
The combination of medications to treat or modify postprandial whether postprandial hyperglycemia has a unique role in the
hyperglycemia include agents that specifically target PPHG, pathogenesis of diabetic vascular complications and should be
including a-glucosidase inhibitors, short-acting insulinotropic a specific target of therapy.
agents, amylin analogues, glucagon-like peptide-1 (GLP-1) However, this alarmingly suggestive body of evidence for a
analogues, dipeptidyl peptidase-IV (DPP-IV) inhibitors, and harmful effect of postprandial hyperglycemia on diabetes
rapid-acting insulin analogues. complications has been sufficient to influence guidelines
a-Glucosidase inhibitors such as acarbose, miglitol and voglibose from key professional bodies, including the World Health
inhibit intestinal tract a-glucosidases and pancreatic a-amylase. Organization, the American Diabetes Association, the American
Although monotherapy with these agents reduces overall HbA1c College of Endocrinology, the International Diabetes Federation,
values less than sulfonylureas or metformin, these are useful the Canadian Diabetes Association, and, more recently, a large
when PPHG is difficult to control. Short-acting insulinotropic task force of European scientific societies focused on CVD.
agents, including repaglinide and nateglinide, dissociate faster Therefore, the real question seems to be, as recently underlined
from their receptors than the sulfonylureas, mitigating the also by the American Diabetes Association, “because CVD is the
potential for delayed hypoglycemia although having a similar major cause of morbidity and mortality in patients with diabetes,
overall incidence of hypoglycemia. Rapid-acting insulin and in type 2 diabetes in particular, understanding the impact
analogues such as insulin lispro or aspart are absorbed quickly on CVD events of treatment directed at specifically lowering
but have a shorter duration of action than that of regular human postprandial glucose is crucial.” To address this fundamental
insulin. When taken just prior to meals, they target PPHG. question, future studies must be specifically designed to evaluate
Pramlintide, an analogue of the glucoregulatory peptide amylin, this new issue, which may significantly change the therapeutic
which is deficient or suppressed in patients with diabetes, lowers approach to diabetes.

With Best Complements From

Mcleods
Makers of
Bio D3 plus
Orcerin and Orcerin GM

13
Vol. 5, Issue 3 & 4 April - Sept 2007
 Reading List
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A, Eschwège E: High blood glucose concentration is a risk
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M, Bais B, Marra G, Tonutti L, Taboga C, Motz E: Role of
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Laakso M, the STOP-NIDDM Trail Research Group: Acarbose
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Cifkova R, Dallongeville J, Ebrahim S, Faergeman O, Graham
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Societies on Cardiovascular Disease Prevention in Clinical
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Practice: European guidelines on cardiovascular disease
prevention in clinical practice. Eur Heart J 24:16011610,
2003
18. de Vegt F, Dekker JM, Ruhè HG, Stehouwer CDA, Nijpels
GBLM, Heine RJ: Hyperglycaemia is associated with all-
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2 diabetes. Diabetes 48:937-942, 1999
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29. Stratton IM, Adler AI, Neil HAW, Matthews DR, Manley
SE, Cull CA, Hadden D, Turner RC, Holman RR, the UK
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W, Henkel H, Hanefeld M: Postchallenge plasma glucose
and glycemic spikes are more strongly associated with
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glucose control with sulphonylureas or insulin compared
with conventional treatment and risk of complications in
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853, 1998
33. Van Gaal LF, De Leeuw IH. Rationale and options for
combination therapy in the treatment of type 2 diabetes.
Diabetologia 2003; 46 (suppl 1):M44-M50.
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Geneva, World Health Org. 1999
 The Evolving Role of the
Family Physician and Family Medicine
Atul Gandotra

Atul Gandotra
GM - Marketing and
Business Development
Pushpanjali Health Care
The family Physician is the first point of contact
in a majority of situations, and often functions
as patient’s primary means of entry into the
healthcare system. There the Family Physician
needs to develop a special relation and bonding
with the patient and their family members. This
bond also acknowledges the many roles played
by the doctor as he or she not only treats the
patient but is a referral point, a health educator
and a guide on general health and hygiene
related needs of the society / community.
On the professional front, the family Physician
is an advocate in dealing with other medical
professionals / Institutes / Hospitals etc for his
patients.
For a family Physician, family Medicine is
unique at it centers round patient - physician
relationship with the patient viewed in the
context of the family. It is the extent of which
this relationship is valued, developed, nurtured
and maintained that distinguishes family
medicine from all other specialties and family
physician from all other specialists.
The scope of an individual family physician’s
practice changes over time, evolving as
competency in current skills is maintained
and new knowledge is obtained through
continuing medical education. this growth in
medical information also confers on the family
physician a responsibility for the assessment of
new medical technology and for participation
in resolving ethical dilemmas brought about by
the technological advances.

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15
Vol. 5, Issue 3 & 4 April - Sept 2007

S. K. Wangnoo
Senior Consultant
Endocrinologist
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Tarunika Bawa
Clinical Assistant
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Vol. 5, Issue 3 & 4 April - Sept 2007
Insulins in Clinical Practice – An Overview
The Diabetes Control and Complications
Trial1 provided conclusive evidence that strict
glycemic control reduces the incidence and
progression of neuropathy, nephropathy, and
retinopathy in patients with type 1 diabetes.
Data from the Wisconsin Epidemiologic Study,
the UK Prospective Diabetes Study (UKPDS)2 ,
and several other trials have suggested a strong
correlation between glycemic control and
complications in patients with type 2 diabetes.
In addition, the UKPDS put to reast concerns
about the potential escalation of atherosclerosis
with the use of insulin or sulfonylureas.
Fortunately, as our understanding of the
importance of strict glycemic control has come
into focus, our ability to achieve this goal has
improved. Much of this newfound ability to
obtain a level close to the euglycemic index
in patients with diabetes can be attributed to
novel insulin molecules that scientists have
synthesized in the past decade.
Research in the insulin arena has focused on
new formulations, novel insulin molecules,
and various methods of insulin delivery that
more closely approximate normal physiologic
insulin response than conventional
preparations. Insulin therapy evolved from
the use of crude animal extracts available
shortly after the discovery of insulin in 1922
by Frederick Banting and Charles Best to
new formulations developed in the 1930s,
1940s, and 1950s. More purified products
were developed in the 1960s, followed by
recombinant human insulin in the 1980s and
insulin analogues in the 1990s. Today, insulin
therapy holds the promise that non-injection
delivery methods will become available in the
near future. The evolution of insulin therapy
already has produced more effective delivery
methods for better glycemic control with fewer
side effects.
Conventional insulin preparations have
pharmacokinetic profiles that do not closely
imitate normal insulin secretory patterns. By
comparison, the pharmacokinetic profiles of
the insulin analogues are able to closely mimic
these patterns with an exogenous insulin
product. The first recombinant DNA human
insulin analogue, insulin lispro (Humalog),
was approved in July 1996 by the US Food
and Drug Administration (FDA). Since then,
two additional analogues, insulin glargine
(Lantus) and insulin aspart (NovoLog), have
been approved. Other insulin analogues and
delivery systems are being evaluated.
17
S. K. Wangnoo1 and Tarunika Bawa2
Historic Achievements in Insulin
Therapy
On January 11, 1922, 14-year-old, 65-lb Leonard
Thompson became the first patient to receive
insulin3 . His blood glucose level fell slightly
with each 15-mL injection and an abscess
developed at the site of one injection. The
extraction process was improved, and insulin
was soon commercially available. The 1923
Nobel Prize in Medicine was awarded to Sir
Fredrick Grant Banting and John MacLeod at
the University of Toronto for the discovery of
insulin.
The first commercial insulin preparation, Iletin,
was relatively fast-acting, and administration
during the middle of the night often was
required4 . Because of these limitations, a
search for new insulin formulations with
differing time-action profiles was launched.
The first long-acting insulin, protamine
zinc insulin, was introduced in the 1930s.
This formulation contained insulin, the
protein protamine, and zinc. NPH insulin, an
intermediate-acting formulation containing
stoichiometric quantities of protamine and
zinc, was introduced in the 1940s. The lente
series, including semilente, lente, and ultralente
preparations, was introduced in the 1950s;
these formulations contained various amounts
of zinc. Advances in chromatography in the
1960s and 1970s led to the production of more
highly purified insulins.
In the 1980s, human insulin became the first
pharmaceutical agent to be produced through
recombinant DNA technology. Limitations in
the time-action profiles of conventional insulins
prompted the search for insulin analogues
with profiles that more closely approximated
normal physiologic insulin secretory patterns.
To date, more than 300 insulin analogues have
been produced4, and three are commercially
available. Because of the search for alternative
delivery methods, pulmonary, buccal, and
perhaps even transdermal insulin delivery
systems are on the horizon.
Normal Insulin Secretion
In the past, one of the significant problems with
insulin therapy was the inability to mimic normal
insulin secretory response with subcutaneously
injected conventional exogenous insulins.
Normal endogenous insulin secretion can be
classified as basal or postprandial. Basal insulin
secretion is responsible for the maintenance
of basal glucose homeostasis. Basal insulin
also governs the rate of hepatic glucose production, precluding
the overproduction of glucose through gluconeogenesis and
glycogenolysis in healthy persons without diabetes.
Basal insulin is secreted at a varying rate of about 0.5 to 1 U/hr
in adults without diabetes5. This secretion maintains serum
concentrations at 5 to 15 microunits/mL (36 to 108 pmol/L)4.
Secretion occurs continuously between meals and throughout
the night. Insulin regimens that used intermediate-acting or long-
acting insulin in an attempt to mimic this basal secretory pattern
have been superseded by the basal insulin analogue glargine.
Postprandial, or stimulated, insulin secretion occurs in response
to a meal or snack and results in insulin concentrations of 60
to 80 microunits/mL (430 to 574 pmol/L) just before a meal and
up to 30 minutes after it. Insulin concentrations return to basal
levels quickly (within 2 to 4 hours)4. The monomeric analogues,
lispro and aspart, more closely approximate this pattern than
regular human insulin.
Problems with Conventional Insulin
The goal of exogenous insulin regimens in patients with
diabetes is to provide physiologically correct insulin profiles.
However, when injected subcutaneously, commercially prepared
conventional insulin formulations have time-action profiles
that do not closely approximatea normal physiologic insulin
secretion
So-called rapid-acting regular human insulin has an onset of
activity from a half hour to an hour after injection, may not reach
peak concentration for 4 hours, and has a duration of action of
up to 8 hours4. Regular human insulin has a strong affinity for
self-association. Thus, the hexameric form (eight closely bound
molecules) is the most prevalent form in a solution of regular
human insulin. To be absorbed, the hexamer must dissociate to
a dimer and further dissociate to a monomer6 . The monomeric
form can then be absorbed into the capillary beds surrounding the
subcutaneous reservoir. The rate-limiting step in the absorption
of regular insulin is dissociation to the monomeric form.
The pharmacokinetic and pharmacodynamic profiles of regular
human insulin present several problems for the patient. First,
regular human insulin is inconvenient to use because the
patient must carefully time the insulin injection to 30 minutes
or more before a meal. Second, between-meal hypoglycemia can
be a problem with regular human insulin, because although it
sometimes reaches peak concentrations 2 hours after injection,
in many cases and depending on the dose it may not peak for 4
to 6 hours after the injection, when glucose levels already may
be low.
The so-called intermediate-acting human insulin, NPH and
lente, yield peak concentrations 4 to 10 hours after injection.
The effective duration of action of these insulin is 10 to 20 hours.
When used as basal insulin, these products present two major
problems: they have a definite peak effect, and their duration of
action necessitates more than one daily injection. Lastly, human
ultralente has an effective duration of 16 to 20 hours. It also
presents several problems when used as a basal insulin 7 : (1)
its onset of action is variable, (2) its peak effect is difficult to
predict, and (3) its duration of action is almost always less than
24 hours.
Rapid-acting Analogues
Because of the previously mentioned problems with
the pharmacokinetic and pharmacodynamic profiles of
subcutaneously administered regular human insulin, rapid-
18
Vol. 5, Issue 3 & 4 April - Sept 2007
acting insulin analogues have been sought after. The ideal short-
acting insulin analogue or monomeric insulin would have a time-
action profile with an onset of less than 1 hour, a duration of less
than 4 hours, and similar effects in all patients4. Additionally,
the hypoglycemic potency of the analogue would be equal to or
greater than that of human insulin. Lastly, the ideal analogue
would be non-immunogenic, chemically stable, and mixable
with other insulins and analogues. Two rapid-acting analogues,
lispro and aspart, are available in the United States.
Insulin Lispro
The pharmacologic effects of lispro are well reviewed. The amino
acid composition of lispro is identical to that of human insulin
except that the positions of the amino acids at B28 and B29 are
reversed. Lispro has a rapid onset of action (15 minutes), and
its action peaks in 30 to 60 minutes and lasts about 3 hours8.
It has proved to be an effective and safe postprandial insulin
analogue with a time-action profile that closely mimics normal
postprandial insulin response.
A more recent insulin formulation contains 75% neutral
protamine lispro and 25% lispro (Humalog Mix75/25). Mixtures
of lispro and intermediate-acting insulins have proved effective;
however, lispro reacts with isophane insulin over time. In
neutral protamine lispro, the lispro has been cocrystallized
with protamine to yield an intermediate-acting formulation
with a time-action profile similar to that of isophane insulin.
A recent comparative trial9 between Humalog Mix75/25 and
human insulin 70/30 showed that Humalog Mix75/25 improved
postprandial glycemic control with comparable overall control.
Insulin Aspart
Aspart was approved by the FDA in June 200010 . This insulin is
identical to human insulin except for the substitution of aspartic
acid for proline at position B28. This rapid-acting insulin
analogue controls postprandial glycemic excursions similarly to
lispro.
In  a  study  comparing  the  pharmacokinetics  and
pharmacodynamics of aspart with regular human insulin11,
aspart peaked earlier (52 minutes versus 145 minutes) with a
higher concentration (41 microunits/L versus 18 microunits/L
[129 pmol/L]), had a shorter mean residence time (149 minutes
versus 217 minutes), and had an earlier peak glycemic effect
(94 minutes versus 226 minutes) than regular human insulin.
Although some preliminary comparisons of aspart with lispro
have suggested that they are similar, others have reported
differences12. Therefore, it is premature to suggest that these
analogues are interchangeable.
Basal Insulin Analogues
The ideal basal insulin would have a peakless effect, a long half-
life, once-daily dosing, and little interpatient or intrapatient
variability. The conventional long-acting and intermediate-
acting insulins that have been used for basal control have
pharmacokinetic profiles that make them difficult to use. In
addition, they do not mimic normal basal insulin secretion.
Finally, after many years of research, a true basal insulin has
been introduced to the market: glargine.
Insulin Glargine
This human insulin analogue, produced by recombinant DNA
technology through nonpathogenic Escherichia coli, differs only
slightly in structure from human insulin13 . Glargine has both
the addition of two arginines at the C terminus of the B chain
and the substitution of glycine for asparagine at position A21.
This slight change in structure yields a molecule that is soluble
at a pH of 4 but has a relatively slow solubility when injected
into a neutral pH environment. When glargine is injected,
microprecipitates form, and slowly the insulin is resolubilized
and absorbed. This sequence of changes is predictable and
provides a relatively constant level of insulin with no discernible
peaks over a period of 24 hours.
A plethora of trials have demonstrated the effectiveness and safety
of glargine in patients with type 1 or type 2 diabetes. Some studies
have suggested that glargine is associated with less hypoglycemia
than NPH insulin.14,15 These studies concluded that insulin
glargine given once daily is as effective as one injection of NPH
insulin in its effect on glycemic control, and glargine resulted
in better predinner glucose levels in one trial. The studies also
concluded that patients who received glargine experienced a
statistically significant reduction in nocturnal hypoglycemia
compared with patients who received NPH insulin.
Glargine offers a reasonable alternative to other long-acting or
intermediate-acting insulins for introducing insulin therapy to
patients with type 2 diabetes who were previously taking oral
antidiabetic agents. It also offers a reasonable alternative for
patients with type 2 diabetes who use one or two injections of
NPH insulin in combination with either oral agents or rapid-acting
insulins. Lastly, glargine is effective as a basal insulin when used
with rapid-acting insulins in patients with type 1 diabetes.
Insulin Detemir
Detemir, another long-acting insulin analogue, is currently being
investigated. This compound is a soluble basal insulin analogue
with a neutral pH and a unique mechanism for providing a
smooth, prolonged time-action profile16 . Detemir apparently
has a high affinity for serum albumin, and its binding may
account for the protracted action17 .
However, on the basis of limited data, it appears that detemir
may not have a duration of action to allow once-daily dosing.
One report18 stated that at therapeutically relevant doses, the
analogue’s duration of action is only 20 hours. This could mean
that to achieve around-the-clock basal coverage, two injections
per day would be required. Interestingly, at least one study18
has suggested that detemir has a greater effect on hepatic glucose
production and a lesser effect on peripheral glucose utilization
than NPH insulin in patients with type 1 diabetes. If this effect is
significant in patients with type 2 diabetes, detemir may offer a
perquisite not found in other insulins.
Conclusion
A large body of evidence has proven conclusively that
strict glycemic control in patients with diabetes reduces the
appearance and progression of chronic complications. Strict
glycemic control without significant hypoglycemia is the
most salient goal of insulin therapy. To achieve this objective,
insulin regimens that closely mimic physiologic insulin
secretory patterns must be used. The older conventional insulin
products do not have time-action profiles that closely mimic
normal secretory patterns; therefore, all of these products have
problems associated with their use. Insulin analogues with more
appropriate pharmacokinetic and pharmacodynamic profiles,
both rapid-acting (postprandial) and long-acting (basal), are now
available. Three of these analogues - lispro, aspart, and glargine
- have been widely studied, and others are in the early stages of
development. These analogues offer the physician the ability to
19
Vol. 5, Issue 3 & 4 April - Sept 2007
closely approximate endogenous insulin secretory patterns with
subcutaneously injected exogenous insulin, improving glycemic
control with less hypoglycemia.
References
1 The effect of intensive treatment of diabetes on the
development and progression of long-term complications in
insulin-dependent diabetes mellitus. The Diabetes Control
and Complications Trial Research Group. N Engl J Med
1993;329(14):977-86
2 Intensive blood-glucose control with sulphonylureas or
insulin compared with conventional treatment and risk of
complications in patients with type 2 diabetes (UKPDS 33).
UK Prospective Diabetes Study (UKPDS) Group. Lancet
1998;352(9131):837-53
3 Bliss M. The discovery of insulin. Chicago: University of
Chicago Press, 1982:112-3
4 White JR Jr, Campbell RK, Hirsch I. Insulin analogues:
new agents for improving glycemic control. Postgrad Med
1997;101(2):58-70
5 Setter S, White J, Campbell RK. Diabetes mellitus. In: Herfindal
T, Gourley D, eds. Textbook of therapeutics: drug and disease
management. 7th ed. Philadelphia: Lippincott Williams &
Wilkins, 2000:377-406
6 Brange J, Owens DR, Kang S, et al. Monomeric insulins and
their experimental and clinical implications. Diabetes Care
1990;13(9):923-54
7 Scholtz HE, et al. (Abstr) Diabetologia 1999;42 (Suppl 1):
A235
8 Campbell RK, White JR Jr. Insulin therapy in type 2 diabetes.
J Am Pharm Assoc (Wash) 2002;42(4):602-11
9 Roach P, Yue L, Arora V. Improved postprandial glycemic
control with Humalog Mix25, a novel protamine-based insulin
lispro formulation. Humalog Mix25 Study Group. Diabetes
Care 1999;22(8):1258-61
10 Setter SM, Corbett CF, Campbell RK, et al. Insulin aspart:
a new rapid-acting insulin analog. Ann Pharmacother
2000:34(12):1423-31
11 Home PD, Barriocanal L, Lindholm A. Comparative
pharmacokinetics and pharmacodynamics of the novel rapid-
acting insulin analogue, insulin aspart, in healthy volunteers.
Eur J Clin Pharmacol 1999;55(3):199-203
12 Chapman TM, Noble S, Goa KL. Insulin aspart: a review of its
use in the management of type 1 and 2 diabetes mellitus. Drugs
2002;62(13):1945-81
13 Levien TL, Baker DE, White JR Jr, et al. Insulin glargine: a new
basal insulin. Ann Pharmcother 2002;36(6):1019-27
14 Yki-Jarvinen H, Dressler A, Ziemen M. Less nocturnal
hypoglycemia and better post-dinner glucose control with
bedtime glargine compared with bedtime NPH insulin during
insulin combination therapy in type 2 diabetes. Diabetes Care
2000;23(8):1130-6
15 Rosenstock J, Riddle M, Dailey G, et al. Treatment to target:
feasibility of achieving control with the addition of basal
bedtime insulin glargine (Lantus) or NPH insulin in insulin-
naive patients with type 2 diabetes on oral agents. HOE901/4002
Study Group. (Abstr) Diabetes 2001;50(Suppl 2):A129
16 Vague P, Selam JL, Skeie S, et al. Insulin detemir is associated
with a more predictable glycemic control and lower risk of
hypoglycemia compared to NPH insulin in subjects with type
1 diabetes. (Abstr) Diabetes 2002;51(Suppl 23):A116
17 Jacobson LV, Popescu G, Plum A. Pharmacokinetics of insulin
detemir in patients with renal or hepatic impairment. (Abstr)
Diabetes 2002;51(Suppl 23):A102
18 Pieber TR, Plank J, Goerzer E, et al. Duration of action,
pharmacodynamic profile and between-subject variability
of insulin detemir in subjects with type 1 diabetes. (Abstr)
Diabetes 2002;51(Suppl 23):A214
 Monitoring of Glycaemic Status
The two large randomized trials DCCT
and UKPDS have clearly established the
relationship between glycemic control and
diabetic complications. Further, it was also
established that there is no glycemic threshold
above normal glycemia for complications have to work together as a team. Both have to
to set in.
Achieving glycemic control means knowing the
targets and accordingly planning the line of
treatment. Glycemic targets are assessed by
measurement of blood sugars and glycosylated
hemoglobin (HbA1c). As supported by different
studies one needs to maintain fasting plasma
glucose between 80-100 mg/dl, 2-hour post
meals (all meals) < 140-150 and pre-meals 90-
130 mg/dl and HbA1c < 6.5-7 %. However,
these general targets need to be individualized
based on the severity of diabetic complications,
frequency of hypoglycemia including
hypoglycemic coma, fertility issues, pre-
pregnancy, antenatal, age, co morbid medical
problems, life expectancy, etc. Special
considerations need to be given while managing
children, pregnant women and elderly. Further,
targets can be subdivided as short term
(temporary) and long term (the ultimate).
Several aspects need to be considered for
monitoring like mode of treatment (diet alone,
OHAs, insulin), laboratory or home glucometer,
frequency, adjustment of dosages, dietary/
exercise schedules and time frame to achieve
the targets. A patient on lifestyle management
alone needs to achieve and maintain the
same strict targets as a patient on Insulin.
The frequency of monitoring may however
differ. On diet alone, it is still reasonable to
monitor blood sugars once in two weeks. On
OHAs, once a week monitoring till targets are
achieved, is highly suggested and thereafter
can be less frequent, say, once in 10-14 days.
If glycemic control rises beyond the target
levels then monitoring needs to be intensified.
Patients on insulin must be monitored more
frequently, daily to once in three days and
optimally two to three times a day. Type 1
diabetics and pregnant women need to check
levels three or more times daily. It is preferable
to control pre meal random blood sugar (RBS)
before targeting post meals. HbA1c, which
gives average glycemia in preceding two to
Neeru Gera three months, should be assessed at first visit
Senior Consultant and then every three months. Once the patient
Endocrinologist shows controlled glycemic status for several
Max Hospital
months then A1c testing can be reduced to
Delhi.
every six months.
21
Vol. 5, Issue 3 & 4 April - Sept 2007
Neeru Gera
Every patient demonstrates their own glycemic
pattern. Hence, it is necessary for the treating
physician to understand this pattern, decide
the medications and subsequently monitor
accordingly. Further, the physician and patient
have a proactive approach, high motivation
level, patience and an interactive dialogue.
The physician must spend time with the
patient and their family to discuss the line
of treatment, practical ways to achieve targets
and the time frame of reaching the target.
Education is the key to diabetic management.
Special situations need to be addressed. In
addition to a regular schedule, patients need
to be educated about days of sickness, travel,
eating out etc. Acute sickness leads to a brittle
state, prone for both hyper (due to insulin
resistance of stress) and hypoglycemia (low
appetite/vomiting etc). Under these conditions
it becomes important to check blood sugars
three to four times-a-day daily random rather
than for strict 2-hour PPBS. The target should
still be to keep all random checks less than
180-200 mg/dl. This requires frequent contact
with the doctor and modification of dosages of
insulin/OHAs. Encourage patients to eat every
two to three hours like fruits/biscuits/curd/
milk/bread/rice/cereal etc. Any hypoglycemic
episode mandates frequent monitoring at least
for that day. After correcting hypoglycemia, a
recheck of blood sugars after half an hour and
again two to three hours later must be done.
This is to ensure that the acute episode has
been corrected with no further recurrence.
During traveling days, patients need to be
encouraged to check blood sugars but as per
their convenience. The most practical time
is to check fasting sugar before dinner, if
possible. Patients on insulin must check daily
and those on OHA at least twice a week. When
traveling for longer periods, dosages need to
be adjusted without waiting to return. Thus,
before traveling the patient must be educated
about self adjustment of insulin/OHA doses.
Eating out may also lead to fluctuating blood
sugars if the meal is very different from
the ones eaten usually. Patients should be
encouraged to consult a dietitian to learn
about exchange diets minimize fluctuations.
Blood sugars must be tested two hours after
that meal or immediately after reaching
home. Fasting sugar must also be checked the
following morning. Based on this information
future adjustment in medication dosages
can be easily made. It is easier to titrate doses if a patient
is on insulin. Insulin doses must be adjusted beforehand in
anticipation of the fluctuation it may induce; blood sugars
must be checked in the manner outlined above.
As already highlighted, monitoring can be routinely carried
out from a lab or self glucometer. Since blood sugars need to
be monitored at different times of day and at regular intervals,
patients should be encouraged to own a personal glucometer.
However, certain precautions need to be taken when operating
it. The glucometer must be calibrated with the control solution
and venous plasma glucose, assess technique and maintenance.
Meter readings can vary from lab by +/- 15 % in fasting state.
Despite limitations SMBGs help in revealing the glycemic
trend. The key to management of diabetes is to know one’s
own glycemic profile, since further therapy is based on this
basic information.
It is imperative to extend the outcome of research studies
to practical use. Physicians need to know the implications
of intensive glycemic control, how to achieve them in the
most practical way and then the way forward. One must
individualize the targets. Mere achievement of targets is not
enough; the real practical challenge is to maintain them over a
longer period of time. Good communication, a team approach,
self motivation and periodic assessment of patient’s health
status will result in astute diabetic management.
References
1. American Diabetes Association Position Statement: Standards
of medical care in Diabetes Diabetes Care 30, S4 - S41, 2007
2. American Diabetes Association: Position Statement:
Implications of the United Kingdom Prospective Diabetes
Study. Diabetes Care 25:S28 - S32, 2002

22
Vol. 5, Issue 3 & 4 April - Sept 2007
 Gestational Diabetes
Garima S Gupta1and Tarunika Bawa2

Garima S Gupta
Registrar
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Pregnancy induces progressive change in The optimum period to screen for GDM in
maternal carbohydrate metabolism. As pregnancy is between 24-28 weeks by which time
pregnancy advances insulin resistance and it manifests in 75% of woman who will develop
diabetogenic stress due to placental hormones GDM. If there is suspicion of undiagnosed DM
(HPL, Progesterone, and Estrogen) necessitates or pre extent DM, then screening may be done
compensatory increase in insulin secretion. during the first visit itself9.
When this compensation is inadequate
gestational diabetes (GDM) develops. Pregnancy Maternal Complication in GDM
that occurs in a woman who already has
v Overt diabetes
diabetes is termed Pregestational Diabetes. Both
these conditions are associated with increased v Pre-eclampsia
maternal and fetal morbidity but rarely with v Abortions
mortality. v Traumatic delivery
GDM is defined as any degree of glucose v Preterm labor
intolerance with onset or first recognition during v Toxemia
pregnancy. This definition applies whether
v Recurrent UTI
insulin or only diet modification is used for
treatment and whether or not condition persists
after pregnancy. The prevalence of GDM was Fetal Complication
2% in 19821 (IGT-2%)2 which increased to v Congenital malformation
7.63% in 19913 (IGT 8.2%)4 and doubled to v Birth asphyxia
16.55% in 20025 (IGT-14.5%)6.
v Macrosomia , hypoglycaemia
v Cardiomyopathy
Who is At-Risk for GDM?
v RDS
The expert committee on diagnosis and
classification of diabetes has recommended v Hypercalcemia
that screening may not be necessary in women v Hyperbilirubinemia
who fulfill the criteria given below7. v Polycythemia .
v Age <25 years v Long term effects-Obesity, IGT, Diabetes.
v Weight normal before pregnancy
v Member of an ethnic group with lower ADA Recommendation:
prevalence of GDM 2-step Approach7
v No known diabetics in first degree relatives An initial screening by measuring plasma
glucose 1 hr after 50 g of oral glucose load
v No history of abnormal glucose tolerance
(Glucose challenge test) and perform a
v No histories of poor obstetric outcome. diagnostic OGT on that subset of women
But in the Indian context, recognition of exceeding the glucose threshold values on GCT
glucose intolerance during pregnancy is is the approach of choice.
perhaps more relevant as Indian woman have Carpenter and Coustan Diagnostic Criteria
an 11-fold increase in the risk of developing (ADA has adopted this criteria) 10
GDM as compared to White Caucasian
women8. 100 g OGTT 75 g OGTT
Fasting 95 mg/dl 95 mg/dl
As glucose is toxic to the developing fetus, all
pregnant women ideally should be screened 1 hr 180 180
for glucose intolerance. However, screening is 2 hr 155 155
mandatory in high-risk patients which include
those with: 3 hr 140

v Age >25 years 2 or > venous plasma concentration must be

Tarunika Bawa
Clinical Assistant
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
v Family history of diabetes
v Obesity (pre-pregnancy weight (BMI >25)
v Bad obstetric history
v Glucose in second fasting urine sample.
met or exceeded for positive diagnosis.
WHO Criteria11
WHO recommends using a 75 gm OGTT
(2 hours) with a threshold plasma glucose

25
Vol. 5, Issue 3 & 4 April - Sept 2007
concentration of > 140 mg per dl at 2 hours similar to that of
IGT outside pregnancy.
This criterion is simple and cost effective and is practiced in
many centers.
Monitoring Glycemic Control
The tight glycemic control expected during pregnancy warrants
intensive monitoring. Urine glucose monitoring is not accurate
due to altered renal threshold during pregnancy. Hence glucose
monitoring is the best method using instant blood glucose
reflectance meters. HbA1c will indicate retrospective control,
patients’ compliance and past performance. It is however not
very useful for day-to-day management of gestational diabetes.
Frucostamine estimation would indicate glycemic control for
past 2-3 weeks.
Fetal Evaluation
Mid Pregnancy
(16 20 weeks) to detect fetal anomalies
MS AFP
USG
Fetal Echo
Late Pregnancy
(28 weeks till delivery to assess fetal well being)
Maternal assessment of fetal activity
Non stress test
Contraction stress test
Fetal biophysical profile
Ultrasonography
Lecithin-to-Sphingomyelin (L/S) ratio, lung profile.
Management
The important predictor of fetal outcome is to ensure that
glycemic control is attained immediately before and during
pregnancy. The plasma glucose level of the normal pregnant
woman is <90 and 120 mg% respectively during fasting and non-
fasting states12. Hence, the best fetal outcome can be expected
by maintaining the mean blood glucose level of approximately
105 mg% in pregnant woman.
1) Medical Nutrition Therapy (MNT)
The expected weight gain during pregnancy is 300-400 gm per
week. Total weight gain is 10-12 kg by term; hence mean plan
aims at euglycemia and providing adequate calories to sustain
nutritional levels for the mother and fetus by avoiding excess
weight gain and post prandial glycemia. Calories requirement
depends on age, activity, pre-pregnancy weight and stage of
pregnancy. Ideally an increment of 300 kcal per day above the
basal requirement is needed13. Non-caloric sweeteners may be
used in moderation.
2) Exercise13,14,15
The woman with pregnancy can use arm ergometery or
undertake walks. Such a program results in lower levels of
glycemia. Exercise improves both hepatic glucose output and
peripheral glucose utilization in over weight pregnant diabetics.
Diet and exercise may obviate the need for insulin treatment in
GDM.
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Vol. 5, Issue 3 & 4 April - Sept 2007
3) ADA Recommendation - Insulin
If MNT fails to maintain the goal (fasting and pre-meal
blood sugar 50-80 mg per dl and post prandial blood sugar
<120mg per dl) then insulin may have to be used.16 Due to
decrease in insulin sensitivity, the insulin requirement goes
up especially during latter half of pregnancy. The requirement
may range from 0.7 units per kg per day in first trimester to 1
unit per kg per day in 3rd trimester. It is ideal to use Human
insulin. Most experts now recommend lispro and Aspart
insulin for use in pregnancy.
This recommendation follows the results of the largest
randomized controlled trials involving 322 pregnant women
with type 1 DM over a period of >4 years. The trial revealed
that insulin Aspart significantly improves post prandial
glycemic control in first and third trimester compared to
the improvement observed with human insulin. The risk of
major hypoglycemia was 28% lower for insulin Aspart than
human insulin17. The use of glargine in pregnancy is still
unresolved.
4) OHA’s in Pregnant Diabetics
The most important issues with the use of oral hypoglycemic
agents (OHA) in pregnancy are placental transfer, resultant
tetratogenecity, and congential anomalies18. Sulphonylureas
induce fetal hyperinsulinism and resulting macrosomia and
neonatal hypoglycemia. Firm recommendations for use of OHA
in pregnancy are limited by paucity of level 1 evidence.
Towner et al in 199519 concluded that major neonatal
malformations were associated with high maternal HbA1C
level at initial presentation. A retrospective study on 584
women by Jacobson20 in 2005 comparing Glyburide with
insulin in 316 and 268 patients respectively observed no
significant difference in birth weight, macrosomia and cesarean
delivery. However neonates born to mothers on Glyburide had
prolonged hyperbilirubinemia and longer NICU stay.
Metformin crosses placenta partially in humans21 and does not
alter the placental metabolism of glucose in mice22. Metformin
has been used in pregnant diabetics during first trimester with
favorable outcome23, but these studies had small sample sizes
and were not well controlled21. It has been widely used for
treatment of insulin resistance associated with infertility and
polycystic ovarian syndrome.
Alpha Glucosidase inhibitors and thiozolideneones have
conflicting results in safety of their usage in pregnancy.
According to ADA (2006) Metformin, Acarbose and Glyburide
are category B drugs and all other OHA’s are category C
drugs24. OHA’s should generally be discontinued unless expert
clinical explanations or consensus is available.
A study by Karlson and Kjellmen25 showed that perinatal
mortality is proportional to maternal blood glucose level
during last 2 weeks of pregnancy.
MBG Perinatal mortality
>150 mg% 24%
100-150 15%
<100 4%
In GDM, the requirement of insulin will fall precipitously
and no insulin may be required after expulsion of placenta.
Gestational diabetic women require follow up and glucose
tolerance test (GTT) after 6 weeks and thereafter at the 6th
month, and annually to determine whether the glucose tolerance
has return to normal. Around 25 % of woman developed DM in
later years.
These pregnancies must be classified as high risk and v Examine utilization of different guidelines among provider
are to be taken special care of by a team consisting of
diabetologist, obstetrician and neonatologist. A short term
intensive care not only results in safe motherhood but
also gives a long term pay off in primary prevention of obesity, IGT
and diabetes in offspring as “Prevention starts before birth”.
References
1. Agarwal S, Gupta AN. Gestation diabetes. J Assoc Physicians India
1982; 30:203
2. Ramachandran A, Jali MV, Mohan W et aI. High prevalence of diabetes
in an urban population in south India. BMJ 1988; 297(6648):587-90.
3. Narendra J, Munichoodappa C. Prevalence of glucose
intolerance during pregnancy. Int J Diab Dev Countries 1991:
11:2-4.
4. Ramachandran A, Snehalatha C, Dharmaraj D, et al. Prevalence
of glucose intolerance in Asian Indians. Diabetes Care 1992;
151348-55.
5. Seshiah V, Balaji V, Balaji MS et aI. Gestational diabetes
mellitus V in India. J Assoc Physicians India 2004; 52:707-11.
6. Ramachandran A, Snehalatha C, Kapur A, et al. For the diabetes
Epidemiology Study Group in India (DESI). High prevalence of
diabetes and impaired glucose tolerance in India.
7. ADA. Clinical practice recommendations 2002. Diabetes Care.
2002;25 ( Suppl 1)
8. Domhost A, Paterson Cichols JS, Wadsworth J, Chiu DC,
Elkeles RS. High prevalence of GDM in women from ethnic
minority groups. Diabetic Med 1992; 9(9):820-2 .
9. Seshiah V, Cynthia Alexandelaji V, et al. Glycemic control from
early weeks of gestation and pregnancy outcome. Diabetes
2006;55 (suppl 1): A 604).
10. ADA Clinical Practice Recommendations. Diabetes Care
2006;29 (supplement 1): S28
11. WH0 study group prevention of diabetes mellitus - Geneva.
World Health Org. 1994. (Tech report series 844).
12. Jovanovic-Peterson L. The Diagnosis and management of gestational
diabetes mellitus. Clin Diabetes 1995; 13:32.
13. Peterson LJ, Peterson CM. Pregnancy in the diabetic woman.
Endocrine and Metab Clin North America 1992; 21:433-54.
14. Kitzmiller JL, Gavin LA, Gin GO, et al. Preconceptual care of
diabetic glycaemic control prevents congenital IN’ anomalies.
JAMA 1991; 265:560-80.
Health is certainly more valuable than money, because it is by health that money is procured;
but thousands and millions are of small avail to alleviate the tortures of the gout to repair
the broken organs of sense, or resuscitate the powers of digestion. Poverty is indeed, an evil
from which we naturally fly; but let us not run from one enemy to another, nor take shelter
in the arms of sickness.
27
Vol. 5, Issue 3 & 4 April - Sept 2007
Research Gaps
v Determine which recommendation produce better pregnancy
and long term outcome.
types.
v Examine barriers to compliance among woman with
gestational diabetes.
v Research ways to support and optimize compliance.
v Research ways to support and optimize compliance.
15. Clapp JF, Rokey R, Treadway JL, et al. Exercise in Ed pregnancy.
Med Sci Sports Exerc 1992; 24:5294:
16. Jovanovic L, Bevier WC, Peterson CM. The Santa Barbara
@County Health Care Services Program: Birth weight
change I Q concomitant with screening for and treatment of
glucose - intolerance of pregnancy: A potential cost-effective
intervention. Am J PerinatoI 1997; 14:221-8
17. Hod M, Visser G, Damm P, et al. Safety and perinatal outcome
in pregnancy: A randomized trial comparing insulin Aspart
with human insulin in 322 subjects with type 1 diabetes.
American Diabetes Association. Poster 1805-P. Diabetes 2006,
June Supplement
18. Pneece R, Jovanovic L. New and future diabetes therapies: are
they safe during pregnancy. J Matrn Fetal Neontal Med 2002;
12(6):365-75.
19. Towner D, Kios SL, Leung B, et al. Congenital malformations
in pregnancies complicated by Type- 2 DM. Diabetes Care
1995; 18:1446-51
20. Gavin F, Jacobson MD, Gladys A, et al. Comparison of glyburide
and insulin for the management of gestational diabetes in a
large managed care organization. Am J Obstet Gynaecol 2005;
193:118-24.
21. Briggs CG, Freeman RK, Yaffe SJ. Drugs in pregnancy to
lactation. 5th ed. Williams and Wilkins, 1998.
22. Denno KM, Sadler TW. Effects of the biguanide class of oral
hypoglycemic agent on mouse embryogenic. Teratology 1994;
49:389.
23. Elliot B, Langer 0, Schenker S, Johnson RF. Comparative
placental transfer of OHA’s in humans. A model of human
placental drug transfer. Am J Obstet Gynaecol 1994;171: 653-
60.
24. Coetzee EJ, Jackson WPU. Oral hypoglycemis in the first
trimester and fetal outcome. S Afr Med J 1984; 65:635-7
25. Karlsson K, Kjellmer I. The outcome of diabetic pregnancies
in relationship to the mother’s blood sugar level. Am J Obstet
Gynaecol 1972; 112:213-20.
Johnson

S. K. Wangnoo
Senior Consultant
Endocrinologist
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Tarunika Bawa
Clinical Assistant
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Vol. 5, Issue 3 & 4 April - Sept 2007
Diabetic Dyslipidemia
Introduction
Type 2 diabetes is associated with a two- to
four-fold excess risk of coronary heart disease
(CHD) according to ATP III/NANHES. Although
the degree of glycemia in diabetic patients is
strongly related to the risk of micro vascular
complications (retinopathy and renal disease),
the relation of glycemia to macro vascular
disease in type 2 diabetes is more modest. The
finding of increased cardiovascular risk factors
before the onset of type 2 diabetes also suggests
that aggressive screening for diabetes combined
with improved glycemic control alone will not
be likely to completely eliminate excess risk
of CHD in type 2 diabetic patients. Clearly, a
multifactorial approach to prevention of CHD
in type 2 diabetes will be necessary.
The most common pattern of dyslipidemia in
type 2 diabetic patients is elevated triglyceride
levels and decreased HDL cholesterol levels.
The concentration of LDL cholesterol in type
2 diabetic patients is usually not significantly
different from nondiabetic individuals;
however, LDL particles are smaller and more
atherogenic in type 2 diabetics. Diabetic
patients may have elevated levels of non-HDL
cholesterol (LDL plus VLDL).
As in nondiabetic individuals, lipid levels may
be affected by factors unrelated to glycemia
or insulin resistance, such as renal disease,
hypothyroidism, and the frequent occurrence
of genetically determined lipoprotein disorders
(eg, familial combined hyperlipidemia and
familial hypertriglyceridemia). Furthermore,
use of alcohol and estrogen may also contribute
to hypertriglyceridemia.
Trials in Diabetic Dyslipidemia
No clinical trial has been done on the effects
of lipid-lowering agents on subsequent CHD
specifically in diabetic subjects. However, a
number of clinical trials have included small
numbers of adult type 2 diabetic subjects. In
the Scandinavian Simvastatin Survival Study
(4S) trial, simvastatin (HMG CoA reductase
inhibitor or “statin”) significantly reduced
CHD incidence and total mortality (borderline
significantly) in diabetic subjects with high
LDL cholesterol and with previous clinical
CHD. In the Cholesterol and Recurrent Events
(CARE) study, pravastatin reduced CHD
incidence significantly in diabetic subjects with
average LDL levels and with previous clinical
CHD. In the Helsinki Heart Study, gemfibrozil
(fibric acid derivative) was associated with
29
S. K. Wangnoo1 and Tarunika Bawa2
a reduction in CHD in diabetic subjects
without prior CHD (although this result was
not statistically significant). In the Veterans
Affairs High-Density Lipoprotein Cholesterol
Intervention Trial (VA-HIT), gemfibrozil
was associated with a 24% decrease in
cardiovascular events in diabetic subjects with
prior cardiovascular disease.
Lifestyle interventions and Glycemic
Control
Weight loss and increased physical activity
leads to decreased triglyceride and increased
HDL cholesterol levels and also to modest
lowering of LDL cholesterol levels. Diabetic
patients who are overweight should be given
a prescription for Medical Nutrition Therapy
(MNT) and for increased physical activity. The
proportion of saturated fat in the meal plan
should be reduced. Some (but not all) studies
suggest that a high-monounsaturated fat diet
may have better metabolic effects than a high-
carbohydrate diet, although other experts have
suggested that such a dietary modification
may make weight loss more difficult in obese
diabetic patients.
Recommendations of the American Heart
Association for patients with CHD have
suggested that the maximal Medical Nutrition
Therapy (MNT) typically reduces LDL
cholesterol 15-25 mg/dl. Thus, if the LDL
cholesterol exceeds the goal by >25 mg/
dl, the physician may decide to institute
pharmacological therapy at the same time
as behavioral therapy for high-risk patients
(i.e., diabetic patients with a prior myocardial
infarction and/or other CHD risk factors).
In other patients, behavioral interventions
may be evaluated at 6-week intervals, with
consideration of pharmacological therapy
between 3 and 6 months.
Interventions to improve glycemia usually
lower triglyceride levels. In general, glucose-
lowering agents do not change or have
only a modest effect on raising HDL levels.
However, the HDL composition may change
in a direction thought to be antiatherogenic.
Thiazolidinediones may increase HDL and LDL
levels, but the long-term effect of such changes
is not known. LDL cholesterol may decrease
modestly (up to 10-15%) with the achievement
of optimal glycemic control. Since improved
glycemic control may also lower triglyceride
levels, it might also cause a favorable change
in LDL composition.
Treatment Goals pharmacological therapy are an LDL cholesterol level of =130
mg/dl and a goal of <100 mg/dl for LDL cholesterol. Since a
The categories of CHD risk by lipoprotein levels in type 2
large proportion of diabetic patients die before they reach
diabetic patients are shown in table 1. Due to frequent changes
the hospital, a preventive strategy based solely on secondary
in glycemic control in diabetic patients and their effects on
prevention would not be able to “save” large numbers of these
levels of lipoprotein, levels of LDL, HDL, total cholesterol,
diabetic patients. In patients with LDL between 100 mg/dl
and triglyceride should be measured every year in adult
and 129 mg/dl, a variety of treatment strategies are available,
patients. If values fall in lower-risk levels, assessment may be
including more aggressive MNT and pharmacological treatment
repeated every 2 years. In children with diabetes, consideration
with a statin . In addition, if the HDL is <40 mg/dl, a fibric
should be given to measuring lipoproteins after age 2 years,
acid such as fenofibrate might be used in patients with LDL
as suggested by the National Cholesterol Education Program
between 100 and 129 mg/dl.
(NCEP) Report of the Expert Panel on Blood Cholesterol in
Children and Adolescents. In agreement with the earlier ADA consensus panel, increased
triglyceride levels are recognized as a target for intervention.
Table 1: CHD risk by lipoprotein levels in type 2 diabetic
Since recommended LDL levels are considered to be <100 mg/
patients
dl and since many diabetic patients have increased triglyceride
Risk LDL–C HDL-C Triglycerides levels, a large proportion of diabetic patients will have
High >130 <40 >400 elevated levels of both LDL cholesterol and triglycerides. As
such, there is likely to be an increase of diabetic patients on
Borderline 100-129 40-59 150-399 pharmacological therapy and thus an increase in expenditures
Low <100 >60 <150 on pharmacological therapy. However, the clinical trial data
suggest that reduction of LDL cholesterol is associated with
For HDL-C, values are 10 mg% more in females, all values are
reduction in CHD and perhaps over-all mortality. Economic
in mg%
analyses, based on the 4S study, suggest that pharmacological
Optimal LDL cholesterol levels for adults with diabetes are therapy may be cost-effective once indirect costs of CHD are
<100 mg/dl, optimal HDL cholesterol levels are >40 mg/dl, and taken into account.
desirable triglyceride levels are <150 mg/dl. (In women who, The initial therapy for hypertriglyceridemia is behavior
at least when nondiabetic, tend to have higher HDL cholesterol modification with weight loss, increased physical activity,
levels than men, it may be desirable to have even higher and moderation of alcohol consumption (moderate means
HDL cholesterol levels [>50 mg/dl]). However, raising HDL moderate!). In the case of severe hypertriglyceridemia (=1,000
cholesterol levels pharmacologically in diabetic patients is very mg/dl), severe dietary fat restriction (<10% of calories; in
difficult since the most effective agent raising HDL cholesaterol addition to pharmacological therapy) is necessary to reduce
levels is nicotinic acid, which has to be used with caution in the risk of pancreatitis. Improved glycemic control (which has
patients with diabetes. Fibrates can raise HDL cholesterol levels been facilitated by the introduction of new glucose-lowering
significantly without affecting glycemic control. agents and more frequent use of combination therapy) is also
The recommendations for treatment of elevated LDL cholesterol very effective for reducing triglyceride levels and should be
generally follow the guidelines of both the NCEP and a recent aggressively used before the introduction of fibric acids. After
ADA consensus development conference with the following the achievement of optimal glycemic control (or at least after
caveats that pharmacological therapy should be initiated after the achievement of as much improvement as likely to be
behavioral interventions are used. However, in patients with possible), the physician may consider adding a fibric acid.
clinical cardiovascular disease or very high LDL cholesterol The decision to start pharmacological therapy/ treatment is
levels (i.e., 200 mg/dL), pharmacological therapy should be dependent on the clinician’s judgment between triglyceride
initiated at the same time that behavioral therapy is started. levels of 200 mg/dl and 400 mg/dl. Above 400 mg/dl, strong
consideration should be given to pharmacological treatment of
Table 2: Treatment decisions based on LDL cholesterol level in
triglyceridemia.
adults with diabetes.
In contrast, improved glycemic control will only modestly
Medical Nutrition Drug Therapy reduce LDL cholesterol levels, and therefore in diabetic
Therapy patients with both high LDL cholesterol and high glucose
levels, one might simultaneously initiate glucose lowering
Initiation LDL Goal Initiation LDL Goal and statin therapy. In some studies, higher-dose statins are
Level Level moderately effective in reducing triglyceride levels in markedly
hypertriglyceridemic subjects (triglyceride =300 mg/dl). The
With >100 <100 >100 <100 critical issue is that gemfibrozil should not be initiated alone
CHD, PVD in diabetic patients who have undesirable levels of both
or CVD triglyceride and LDL cholesterol. Fenofibrate may have greater
W i t h o u t >100 <100 >130 <100 LDL-lowering effects and may be useful in diabetic patients
CHD, PVD with combined hyperlipidemia. Although HDL cholesterol,
or CVD as noted above, is a powerful predictor of CHD in diabetic
Data are given in milligrams per decilitre patients, it is difficult to raise HDL cholesterol levels without
pharmacological intervention. Nicotinic acid, which should
In the context of the NCEP report, it is suggested that diabetic
be used with caution in diabetic patients, and fibrates can
subjects with clinical CHD and an LDL cholesterol level of
effectively increase HDL cholesterol levels.
=100 mg/dl after MNT and glucose interventions be treated
with pharmacological agents. For diabetic patients without pre- In some cases, combined lipid therapy may be initiated. The
existing CHD, the current ADA recommendations for starting combination of statins with nicotinic acid and especially with

30
Vol. 5, Issue 3 & 4 April - Sept 2007
Table 3: Priorities in Management of Diabetic Dyslipidemia

I. LDL cholesterol lowering

First choice HMG CoA reductase inhibitor (statin)
Second choice Bile acid binding resin (resin) or fenofibrate

II. HDL cholesterol raising
Behavioral interventions such
as weight loss, increased
physical activity, and smoking
cessation may be useful,
Difficult except with nicotinic
acid, which should be used
with caution, or fibrates

III. Triglyceride lowering
Glycemic control first priority
Fibric acid derivative
(gemfibrozil, fenofibrate)
Statins are moderately
effective at high dose in
hypertriglyceridemic subjects
who also have high LDL-C

IV. Combined hyperlipidemia
First choice Improved glycemic control plus high-dose statin
Second choice Improved glycemic control plus statin plus fibric
acid derivative (gemfibrozil, fenofibrate)
Third choice Improved glycemic control plus resin plus fibric
acid derivative (gemfibrozil, fenofibrate)
Improved glycemic control plus statin plus
nicotinic acid (glycemic control must be monitored
carefully)

gemfibrozil or fenofibrate has been associated with increased
risk of myositis, although the risk of clinical myositis (as
opposed to elevated creatinine phosphokinase levels) appears
to be low. However, the risk of myositis may be increased
with the combination of gemfibrozil and cerivastatin (no
longer marketed now) or in patients with renal disease. The
combination of statins with nicotinic acid is extremely effective
in modifying diabetic dyslipidemia (with the largest increases in
HDL cholesterol levels), but the combination may significantly
worsen hyperglycemia. Thus, this combination should be used
with extreme caution: use low doses of nicotinic acid (=2 g
of nicotinic acid per day) with frequent monitoring of glucose
levels. Flushing, a common side effect of starting nicotinic acid,
can be reduced by either taking it with meals or combining
with aspirin. Lipid
Lowering Agents
A brief summary of the actions of available agents for lipid
lowering in patients with diabetes is shown in table 4 below.
Generally, one or two agents are available in each class with the
exception of the statins, for which there are many. The choice
of statin should depend principally on the LDL reduction
needed to achieve the target (<100 mg/dl, on the initial LDL
level, and on the judgment of the treating physician.
Type 1 diabetic patients who are in good control tend
to have normal (and sometimes better than normal)
levels of lipoprotein. Their composition of lipoproteins
may be abnormal, but the effects of these compositional
abnormalities in relation to CHD are unknown. There is
relatively little observational data on lipoproteins and CHD,
and there are no clinical trials relating lipoproteins to CHD.
It seems reasonable that if type 1 diabetic patients have LDL
cholesterol levels that are above the goals recommended for
type 2 diabetic patients, they should be aggressively treated.
Improved glycemic control may be even more important in
type 1 diabetic patients than in type 2 diabetic patients for
reduction of CHD (eg, Wisconsin Epidemiologic Study of
Diabetic Retinopathy [WESDR]).

31
Vol. 5, Issue 3 & 4 April - Sept 2007
Table 4: Actions of available agents for lowering lipids
Risk LDL HDL Triglycerides Trials

First Line
Drugs

HMG CoA 4S (simvastatin)

reductase
inhibitor

Triglyceride CARE
lowering (pravastatin)

Fibric Acid Helsinki

derivative (gemfibrozil)

LDL lowering

Bile acid resins none

LDL and
triglyceride
lowering

Nicotinic Acid none

invites case studies, original,

and review articles on different specialties

Please sumit your contributions by email

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32
Vol. 5, Issue 3 & 4 April - Sept 2007

S. K. Wangnoo
Senior Consultant
Endocrinologist
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Tarunika Bawa
Clinical Assistant
Apollo Centre for Obesity,
Diabetes & Endocrinology
(ACODE) Indraprastha
Apollo Hospital, New Delhi
Vol. 5, Issue 3 & 4 April - Sept 2007
Treatment of Hypertension in Adult Patients
with Diabetes - ADA Guidelines Review
Hypertension (defined as a blood pressure
³140/90 mmHg) is an extremely common is reasonable if it can be safely achieved.
co-morbid condition in diabetes, affecting ~
20-60% of patients with diabetes, depending on
obesity, ethnicity, and age. In type 2 diabetes,
hypertension is often present as a part of the
metabolic syndrome of insulin resistance also
including central obesity and dyslipidemia. In
type 1 diabetes, hypertension may reflect the
onset of diabetic nephropathy. Hypertension
substantially increases the risk of both macro
vascular and micro vascular complications,
including stroke, coronary artery disease,
and peripheral vascular disease, retinopathy,
nephropathy, and possibly neuropathy. In
recent years, adequate data from well-designed
randomized clinical trials have demonstrated
the effectiveness of aggressive treatment of
hypertension in reducing both types of diabetes
complications.
Diabetes increases the risk of coronary events
twofold in men and fourfold in women. Part
of this increase is due to the frequency of
associated cardiovascular risk factors such
as hypertension, dyslipidemia, and clotting
abnormalities. In observational studies, people
with both diabetes and hypertension have
approximately twice the risk of cardiovascular
disease as non diabetic people with
hypertension. Hypertensive diabetic patients
are also at increased risk for diabetes-specific
complications including retinopathy and
nephropathy. In the U.K. Prospective Diabetes
Study (UKPDS) epidemiological study, each
10 mmHg decrease in mean systolic blood
pressure was associated with reductions in
risk of 12% for any complication related to
diabetes, 15% for deaths related to diabetes,
11% for myocardial infarction, and 13% for
microvascular complications. No threshold of
risk was observed for any end point.
The UKPDS and the Hypertension Optimal
Treatment (HOT) trial both demonstrated
improved outcomes, especially in preventing
stroke, in patients assigned to lower blood
pressure targets. Optimal outcomes in the
HOT study were achieved in the group with
a target diastolic blood pressure of ²80 mmHg
(achieved 82.6 mmHg). Randomized clinical
trials demonstrate the benefit of targeting
a diastolic blood pressure of 80 mmHg.
Epidemiological analyses show that blood
pressures ³120/70 mmHg are associated with
increased cardiovascular event rates and
mortality in persons with diabetes. Therefore,
33
S. K. Wangnoo1 and Tarunika Bawa2
a target blood pressure goal of <130/80 mmHg
There is no threshold value for blood pressure,
and risk continues to decrease well into the
normal range.
Dietary management with moderate sodium
restriction has been effective in reducing
blood pressure in individuals with essential
hypertension. Several controlled studies have
looked at the relationship between weight loss
and blood pressure reduction. Weight reduction
can reduce blood pressure independent of
sodium intake and also can improve blood
glucose and lipid levels. The loss of one
kilogram in body weight has resulted in
decreases in mean arterial blood pressure of ~1
mmHg. The role of very low calorie diets and
pharmacologic agents that induce weight loss
in the management of hypertension in diabetic
patients has not been adequately studied. Some
appetite suppressants may induce increases in
blood pressure levels, so these must be used
with care. Given the present evidence, weight
reduction should be considered an effective
measure in the initial management of mild-
to-moderate hypertension, and these results
could probably be extrapolated to the diabetic
hypertensive population.
Sodium restriction has not been tested in
the diabetic population in controlled clinical
trials. However, results from controlled
trials in essential hypertension have shown
a reduction in systolic blood pressure of ~
5 mmHg and diastolic blood pressure of 2-
3 mmHg with moderate sodium restriction
(from a daily intake of 200 mmol [4,600 mg]
to 100 mmol [2,300 mg] of sodium per day).
A dose response effect has been observed with
sodium restriction. Even when pharmacologic
agents are used, there is often a better response
when there is concomitant salt restriction due
to the aforementioned volume component of
the hypertension that is almost always present.
The efficacy of these measures in diabetic
individuals is not known.
Moderately intense physical activity, such
as 30-45 minutes of brisk walking most days
of the week, has been shown to lower blood
pressure and is recommended. The American
Diabetes Association Consensus Development
Conference on the Diagnosis of Coronary
Heart Disease in People with Diabetes has
recommended that diabetic patients who are
35 years of age or older and are planning to
begin a vigorous exercise program should have
exercise stress testing or other appropriate non invasive testing.
Stress testing is not generally necessary for asymptomatic
patients beginning moderate exercise such as walking.
Smoking cessation and moderation of alcohol intake are also
recommended and are clearly appropriate for all patients with
diabetes.
There are a number of trials demonstrating the superiority of
drug therapy versus placebo in reducing outcomes including
cardiovascular events and microvascular complications of
retinopathy and progression of nephropathy. These studies
used different drug classes, including angiotensin-converting
enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs),
diuretics, and ß-blockers, as the initial step in therapy. All of
these agents were superior to placebo; however, it must be noted
that many patients required three or more drugs to achieve the
specified target levels of blood pressure control. Overall there
is strong evidence that pharmacologic therapy of hypertension
in patients with diabetes is effective in producing substantial
decreases in cardiovascular and microvascular diseases.
There are limited data from trials comparing different classes of
drugs in patients with diabetes and hypertension. The UKPDS-
Hypertension in Diabetes Study showed no significant difference
in outcomes for treatment based on an ACE inhibitor compared
with a ß-blocker. There were slightly more withdrawals due to
side effects and there was more weight gain in the ß-blocker
group. In post myocardial infarction patients, ß-blockers have
been shown to reduce mortality. There are numerous studies
documenting the effectiveness of ACE inhibitors and ARBs
in retarding the development and progression of diabetic
nephropathy. ACE inhibitors have a favourable effect on
cardiovascular outcomes, as demonstrated in the MICRO-
HOPE study. This cardiovascular effect may be mediated by
mechanisms other than blood pressure reduction. It is possible
that other drug classes may behave similarly.
Some studies have shown an excess of selected cardiac events
in patients treated with dihydropyridine calcium channel
blockers (DCCBs) compared with ACE inhibitors. Ongoing
trials including the Antihypertensive and Lipid-Lowering
Treatment to Prevent Heart Attack Trial (ALLHAT) study
should help to resolve this issue. DCCBs in combination with
ACE inhibitors, ß-blockers, and diuretics, as in the HOT study
and the Systolic Hypertension in Europe (Syst-Eur) Trial, did
not appear to be associated with increased cardiovascular
morbidity. However, ACE inhibitors and ß-blockers appear
to be superior to DCCBs in reducing myocardial infarction
and heart failure. Therefore, DCCBs appear to be appropriate
agents in addition to, but not instead of, ACE inhibitors and
ß-blockers. Non-DCCBs (i.e., verapamil and diltiazem) may
reduce coronary events. In short-term studies, non-DCCBs
have reduced albumin excretion.
There are no long-term studies of the effect of -blockers, loop
diuretics, or centrally acting adrenergic blockers on long-term
complications of diabetes. The a -blocker arm of the ALLHAT
study was stopped by the data and safety monitoring
committee because of an increase in cases of new-onset
heart failure in patients assigned to the a -blocker. While this
could merely represent unmasking of heart failure in patients
previously treated with an ACE inhibitor or a diuretic, it
seems reasonable to use these as second-line agents when
preferred classes have been ineffective or when other specific
indications, such as benign prostatic hypertrophy (BPH), are
present.
34
Vol. 5, Issue 3 & 4 April - Sept 2007
There is a strong epidemiological connection between
hypertension in diabetes and adverse outcomes of diabetes.
Clinical trials demonstrate the efficacy of drug therapy
versus placebo in reducing these outcomes and in setting an
aggressive blood pressure-lowering target of <130/80 mmHg.
It is very clear that many people will require three or more
drugs to achieve the recommended target. Achievement of
the target blood pressure goal with a regimen that does not
produce burdensome side effects and is at reasonable cost to
the patient is probably more important than the specific drug
strategy.
Because many studies demonstrate the benefits of ACE
inhibitors on multiple adverse outcomes in patients with
diabetes, including both macro vascular and microvascular
complications, in patients with either mild or more severe
hypertension and in both type 1 and type 2 diabetes, the
established practice of choosing an ACE inhibitor as the
first-line agent in most patients with diabetes is reasonable.
In patients with microalbuminemia or clinical nephropathy,
both ACE inhibitors (type 1 and type 2 patients) and ARBs
(type 2 patients) are considered first-line therapy for the
prevention of and progression of nephropathy. However, other
strategies including diuretic and ß-blocker-based therapy are
also supported by evidence. Because of lingering concerns
about the lower effectiveness of DCCBs (compared with
ACE inhibitors, ARBs, ß-blockers, or diuretics) in decreasing
coronary events and heart failure and in reducing progression
of renal disease in diabetes, these agents should be used as
second-line drugs for patients who cannot tolerate the other
preferred classes or who require additional agents to achieve
the target blood pressure. Other classes, including a-blockers,
may be used under specific indications (such as symptoms
of BPH for a-blockers) or other agents have failed to control
the blood pressure or have unacceptable side effects. Blood
pressure, orthostatic changes, renal function, and serum
potassium should be monitored at appropriate intervals.
Treatment decisions should be individualized based on the
clinical characteristics of the patient, including co-morbidities
as well as tolerability, personal preferences, and cost.
Goal (mmHg) <130 <80
Behavioural therapy alone 130-139 80-89
(maximum 3 months) then add
pharmacologic treatment
Behavioural therapy + >140 >90
pharmacologic treatment
v Blood pressure should be measured at every routine
diabetes visit. Patients found to have systolic blood
pressure 130 mmHg or diastolic blood pressure 80
mmHg should have blood pressure confirmed on a
separate day.
v Orthostatic measurement of blood pressure should
be performed to assess for the presence of autonomic
neuropathy.
Patients with diabetes should be treated to a diastolic blood
pressure <80 mmHg
v Patients with a systolic blood pressure of 130-139 mmHg
or a diastolic blood pressure of 80-89 mmHg should be
given lifestyle/behavioral therapy alone for a maximum
of 3 months and then, if targets are not achieved, should
also be treated pharmacologically.
 v Patients with hypertension (systolic blood pressure 140
mmHg or diastolic blood pressure 90 mmHg) should
receive drug therapy in addition to lifestyle/behavioral
therapy.
v Initial drug therapy may be with any drug class currently
indicated for the treatment of hypertension. However,
some drug classes (ACE inhibitors, ß-blockers, and
diuretics) have been repeatedly shown to be particularly
beneficial in reducing CVD events during the treatment
of uncomplicated hypertension and are therefore
preferred agents for initial therapy. If ACE inhibitors are
not tolerated, ARBs may be used. Additional drugs may
be chosen from these classes or another drug class.
v If ACE inhibitors or ARBs are used, monitor renal
function and serum potassium levels.
v In patients with type 1 diabetes, with or without
hypertension, with any degree of albuminuria, ACE
inhibitors have been shown to delay the progression of
nephropathy.
v In patients with type 2 diabetes, hypertension and
micro albuminuria, ACE inhibitors and ARBs have been
shown to delay the progression to macro albuminuria.
v In those with type 2 diabetes, hypertension, macro
albuminuria (>300 mg/day), nephropathy, or renal
insufficiency, an ARB should be strongly considered.
If one class is not tolerated, the other should be
substituted.
v In patients over age 55 years, with hypertension or
without hypertension but with another cardiovascular
35
Vol. 5, Issue 3 & 4 April - Sept 2007
risk factor (history of cardiovascular disease,
dyslipidemia, micro albuminuria, smoking), an ACE
inhibitor (if not contraindicated) should be considered
to reduce the risk of cardiovascular events.
v In patients with a recent myocardial infarction, ß-
blockers, in addition, should be considered to reduce
mortality.
v Patients with diabetes should be treated to a systolic
blood pressure <130 mmHg.
v In patients with microalbuminuria or overt nephropathy,
in whom ACE inhibitors or ARBs are not well tolerated,
a non-DCCB or ß-blocker should be considered.
v If ACE inhibitors or ARBs are used, monitor renal
function and serum potassium levels.
v In elderly hypertensive patients, blood pressure should
be lowered gradually to avoid complications.
v Patients not achieving target blood pressure on three
drugs, including a diuretic, and patients with a
significant renal disease should be referred to a specialist
experienced in the care of patients with hypertension.
References
1. Arauz-Pacheco C, Parrott MA, Raskin P: The treatment of
hypertension in adult patients with diabetes (Technical
Review). Diabetes Care 25:134–147, 2002
2. Bakris GL, Williams M, Dworkin L, Elliott WJ, Epstein M,
Toto R, Tuttle K, Douglas J, Hsueh W, Sowers J: Preserving
renal function in adults with hypertension and diabetes: a
consensus approach. Am J Kid Dis 36:646–661, 2000

Sameer Gulati
Junior Consultant
St. Stephens Hospital
New Delhi
N. P. Singh
Professor
Department of Medicine
and Head of Nephrology
Division, Maulana Azad
Medical College and
Associated Lok Nayak
Hospital, Delhi
B. Mohan Rathi
Research Associate
Department of Medicine,
Maulana Azad Medical
College and associated Lok
Nayak Hospital, New Delhi.
College and Associated Lok
Nayak Hospital, Delhi
Vol. 5, Issue 3 & 4 April - Sept 2007
Rapidly Progressive Glomerulonephritis
Sameer Gulati1, N P Singh2 and B. Mohan Rathi3
Definition: Rapidly progressive glomerulone- Table 2: ANCA positive RPGN
phritis (RPGN)/crescentic glomerulonephritis
is a disease of the kidney that results in Vasculitis Associated with
a rapid decrease in the glomerular filtration medications:
rate of at least 50% over a short period
Microscopic Hydralizine
(a few days to 3 months). 1 The main
polyangitis
pathological finding is fibrinoid necrosis
(>90% of biopsy specimens); and extensive Wegner’s Aminoguanidine
crescent formation is present in at least granulomatosis
50% of glomeruli. RPGN is accompanied
by oliguria or anuria and with features of Churg Strauss Allopurinol
glomerulonephritis including dysmorphic
eryhrocyturia, erythrocytic cylinduria and Anti GBM Propylthiouracil
glomerular proteinuria. Renal diseases other Minocycline
than Crescentic Glomerulonephritis causing
Chronic liver Sjogren’s syndrome
signs and symptoms of Rapidly Progressive
disease with IgA
Glomerulonephritis have been referred to as
nephritis
Pseudo RPGN.
Table 1: Pseudo RPGN without glomerulone- HIV infection Silicosis
phritis
Henoch Schonlein Systemic lupus
purpura erythromatosis
Acute interstial Thromboembolic
nephritis renal disease Monoclonal Polymyositis
gammopathy light
Acute tubular Renal artery chain disease.
Necrosis obstruction
Rheumatoid Other acute or chronic
Scleroderma renal Renal vein thrombosis arthritis infection
Renal Crisis
Pathogenesis of Crescent Formation: Crescent
formation appears to represent a nonspecific
Malignant Hemolytic uremic
response to severe injury to the glomerular
Hypertension syndrome
capillary wall. Rents are induced in the
Light chain Thrombotic glomerular capillary wall, resulting in the
Nephropathy thromboctopenic movement of plasma products into Bowman’s
purpura space with subsequent fibrin formation, the
influx of macrophages and T cells, and the
Classification: There is no uniform classification release of proinflammatory cytokines, such as
of RPGN. The following classification is interleukin-1 and tumor necrosis factor-alpha.
commonly accepted: Clinical Features: The presenting complaints
in RPGN may be similar to those in severe
Type I: Anti-GBM disease without
postinfectious glomerulonephritis: the acute
Pulmonary Hemorrhage
onset of macroscopic hematuria, decreased
Type II: Immune Complex Associated urine output, and edema. More commonly,
Disease (without Anti GBM or however, RPGN has an insidious onset
ANCA) with the initial symptoms being fatigue
or edema. The rate of progression of renal
Type III: Pauci Immune (with ANCA)
failure is variable ranging from few hours
Type IV: Mixed Pattern (with Anti GBM to many months. Hypertension is relatively
and ANCA) uncommon except in patients with diffuse
endocapillary glomerulonephritis, chronic
Type V: Pauci Immune (without ANCA glomerulonephritis or severe fluid overload.
or Anti GBM) Clinical presentation and intensity of RPGN
For practical purposes RPGN has been redefined depends upon histological lesion underlying
into two categories, ANCA positive or ANCA pathogenic process and environmental genetic
negative. influences. The most common prodrome of
37
Table 3: ANCA negative RPGN also reflects response to therapy with reactivation of urine
sediment providing a mirror of reactivation of the disease,
Post Infectious frequently before clinical manifestations.

Viral Miscellaneous Table 4: Clinical manifestation of affected organs or systems

Hepatitis C HIV Legionella Syphilis System Clinical Manifestations

Influenza Mycoplasma Leprosy
Skin Leukocytoclastic vasculitis
Endocapillary Proliferation Sub acute bacterial mostly in lower limbs
endocarditis Nail fold infarcts

Suppurative Infections Shunt nephritis Granulomatous cutaneous

Non Infectious
Systemic
Vasculitis
Polyarteritis nodosa Allopurinol Propylthiouracil
Microscopic polyangiitis
Henoch Schonlein purpura
Churg Strauss syndrome
Behcet’s syndrome
Relapsing polychondritis
Non vasculitis
Malignancy
Cryoglobulinemia Systemic
lupus Erythromatosis Alport
syndrome C 3 nephritic
factor Silicosis
Non systemic
Associated with treatment
Rifampicin Enalapril
Penicillamine Hydralazine
Membrano proliferative
IgG-IgA nephropathy
Membranous nephropathy
Idiopathic Endocapillary
proliferation Without
endocapillary proliferation
Idiopathic Sarcoidosis
nodules in WG, Churg
Strauss syndrome
Painful erythrematous
nodules, focal necrosis,
ulceration and livedo
reticularis due to
necrotizing arteritis
Nervous system Involvement of meningeal
vessels
Seizures
Most common
manifestation of ANCA
associated disease is
Mononeuritis multiplex
Musculoskeletal Symmetrical, migratory
arthritis involving small
joints
Pain and elevation in
tissue enzyme levels

Non Infectious Gastrointestinal Intussusception, pancreatitis

and occult bleeding due to
Systemic Non systemic ischemic ulceration
Renal Most common finding in
Rheumatoid arthritis Anti GBM Antibodies
covert renal disease is
Dermatomyositis Sjogren’s on GBM Goodpasture’s
microscopic hematuria
syndrome Reiter’s syndrome syndrome Goodpasture’s
disease Membranous Respiratory Sinusitis, otitis media, ulcers
nephropathy in the nasal mucosa, and
subglottic stenosis in upper
ANCA-associated vasculitis is flu like symptoms characterized respiratory tract
by malaise, fever, arthralgias, myalgias, anorexia, and Pulmonary hemorrhages and
weight loss. This occurs in more than 90% of patients hemoptysis
and can occur within days to months of the onset of
nephritis or other manifestations of vasculitis. Following Ocular Iritis, uveitis, and
the prodrome, the most common complaints are abdominal conjunctivitis
pain, painful cutaneous nodules or ulcerations, and a
migratory polyarthropathy. When pulmonary or upper
Serological testing: Various serological tests and a variety of auto
airway involvement is present, patients complain of sinusitis
antibodies for different systemic diseases have been advocated
symptoms, cough, and hemoptysis.
as shown in the table, but one should not forget hepatitis
Physical: Hypertension can be present but is not common. profile and HIV testing. The reasons for this include the high
Unless specific findings are present, such as those listed association between various renal diseases and the presence of
below, the physical examination results are usually normal. either Hepatitis B or C, the potential risk of infection to the
physician and clear differences in approach to therapy. HIV
Urinalysis: With rare exceptions, the sediment should contain
testing is also advocated because a few patients with RPGN can
red cells that are dysmorphic, red cell casts, positive dipstick
present in this way.
proteinuria and leucocytes, including leucocyte cast at
times, consistent with renal injury. Staining for eosinophils Chest X ray and stool quaiac: These should be routine parts
should be done because interstitial nephritis and several of evaluation of the patient with RPGN, because malignancy is
other entities present in this fashion.2 The urine analysis significant cause of RPGN and increases with aging.

38
Vol. 5, Issue 3 & 4 April - Sept 2007
Erythrocyte Sedimentation Rate (ESR): This old test remains Renal Biopsy: Renal biopsy differentiates between RPGN and
an essential and inexpensive parameter to follow for evidence Pseudo RPGN and thus the consequent changes in lines of
of disease activity. If it is not elevated at presentation, then management. It is done to assess the degree of glomerulosclerosis
RPGN is much less likely, and if it decreases with therapy, then and interstitial fibrosis as it is highly correlated with prognosis.
this reassures that the inflammatory process is regressing. It also provides a histological index of response in terms of
Table 5 : Laboratory investigations in RPGN crescents present.
Treatment: Early diagnosis with renal biopsy and serologic
Specific
testing and early initiation of appropriate therapy is essential
Anti GBM antibodies Anti GBM disease to minimize the degree of irreversible renal injury. Empiric
ANCA Systemic vasculitis therapy may be begun in patients with severe disease,
particularly if either renal biopsy or interpretation of the
Anti dS DNA antibodies SLE
biopsy will be delayed. Pulse steroids are followed by high
Anti Sm antibody SLE dose alternate day steroids. Oral prednisone is initiated at 2
C3 nephritic factor MCGN type II, sometimes mg/kg and then tapered according to protocol.3 If segmental
ASOT SLE glomerulosclerosis is present on renal biopsy or the ANCA is
Post streptococcal positive oral cyclophosphamide (2 mg/kg daily - may be tapered
glomerulonephritis (titers with a decrease in dose for decreased renal function, low white
may also increase with count or low platelets) is added to the regimen 5 Patients are
hyper-globulinemia and SLE) encouraged to maintain a high intake of fluids to decrease bladder

Anti DNA’ase Post streptococcal Table 6: Therapeutic modalities of the future.

glomerulonephritis (titers
Anti cytokine/receptor agents
may also increase with
Interleukin-1 receptor antagonist
hyper-globulinemia and
SLE) Soluble IL-1 receptor
Non Specific Soluble CR-1
Soluble TNF-á receptor protein
Complement: Mixed essential CTLA4-Ig
Low C4, Normal C3 cryglobulinemia (MEC), SLE
Immunosuppressive
Low C4, C3 SLE, MCGN I, MEC
Deoxyspergualin
Low C3, Normal C4 MCGN II, Postinfectious
glomerulonephritis, Anti-adhesin protein antibodies
sometimes SLE Peptides and mutated/substituted peptides
Immunosorbant columns/Goodpasture’s epitope
Raised C3, C4 ALG (Antilyphocyte globulin)
Cryglobulins MEC, (and others include
SLE, Post infectious Miscellaneous
glomerulonephritis usually at Trapidil, anti platelet
lower levels) Antigen based hetropolymers
Immunoglobulins:
Raised IgG, IgM SLE, Systemic Vasculitis, toxicity. With this regimen, approximately 80% of patients
Postinfectious GN with non-anti-GBM show an improvement, and 75% of dialysis
dependent patients come off dialysis.6 Patients are followed on
Raised IgE Churg Strauss syndrome
this regimen closely with physical examination, biochemical
Raised IgA IgA nephropathy, Henoch studies and ESR with careful urinalysis with stepwise tapering
Schonlein purpura as clinically indicated. Treatment of choice in anti-GBM disease
Paraprotein (IgM) MEC, myeloma is plasmapheresis combined with prednisone combined with
prednisone and cyclophosphamide. RPGN patients who are
Rh factor Most glomerulonephritis,
refractory to prednisone and cyclophosphamide, intraveneous
CRP particularly systemic
gamma globulin has been used with success on the rationale
vasculitis, but usually not
that anti-idiotypic antibodies play a role in the disease
SLE.
process. 7 Monoclonal antibodies directed at lymphocyte
Increased Alkaline Systemic vasculitis surface determinants have also been used in refractory cases. 8
Phosphatase Therapeutic modalities of the future are outlined below:
Non Specific In those patients with pseudo-RPGN or a non glomerular cause
of the clinical syndrome of RPGN, the appropriate diagnosis
Hematology, Neutrophilia, Systemic
needs to be made and appropriate therapy instituted. Diagnostic
Thrombocytosis vasculitis Churg Strauss
and therapeutic approach to patients presenting with clinical
Eosinophilia syndrome
RPGN is outlined in the table below.
Lymphopenia, SLE
Thrombocytopenia Prognosis: The untreated course of RPGN can be devastating,
with most patients progressing to ESRD or death within a
Positive Bacteriological Infection related disease very short period of time. However if an infectious etiology is
Cultures particularly endocarditis involved the course can be much more benign and treatment

39
Vol. 5, Issue 3 & 4 April - Sept 2007
 40
Vol. 5, Issue 3 & 4 April - Sept 2007
of the underlying process can lead to resolution of the disease
process. Poor prognostic factors have included a large number
of crescents, circumferential crescents, severe tubulointerstial
disease, extensive glomerular and interstial scarring, oligonuria,
requirement for dialysis and a serum creatinine level higher
than 6 mg/dl.1,3 Patients with anti-GBM disease and 50% or
more crescents with a serum creatinine of 6 mg/dl or greater
have essentially no expectation of response unless they are also
ANCA positive.3 These ‘double positive’ patients may require
dialysis but 30% to 50% of cases recover from dialysis, unheard
of with pure anti-GBM disease.4 Additionally this subgroup of
patients have more systemic manifestations and more frequent
relapses of their clinical disease, which rarely occurs with pure
anti-GBM disease. There is inverse correlation between ANCA
and anti-GBM titers with clinical disease i.e. patients tend to
have high ANCA titers and low anti-GBM titers.
Summary:
l RPGN results in rapid decrease in GFR of atleast 50% over
a short period. The main pathological finding is fibrinoid
necrosis in > 90% of biopsy specimens and extensive
crescent formation in at least 50% of biopsy specimens
l Patients present with the acute onset of macroscopic
hematuria, decreased urine output, and edema. More
commonly, however, RPGN has an insidious onset with the
initial symptoms being fatigue or edema.
l Renal biopsy is done to differentiate between RPGN and
Pseudo RPGN, besides helping in prognostification and
providing a histological index of response.
l Poor prognostic factors have included a large number of
crescents, circumferential crescents, severe tubulointerstial
disease, extensive glomerular and interstial scarring,
oligonuria, requirement for dialysis and a serum creatinine
level higher than 6 mg/dl.
41
Vol. 5, Issue 3 & 4 April - Sept 2007
l Patients are further classified on the basis of ANCA
positivity.
l The therapy of most patients with RPGN involves pulse
methylprednisolone followed by daily oral prednisone, oral
or intravenous cyclophosphamide, and in some settings,
plasmapheresis.
l Early diagnosis with renal biopsy and serologic testing
and early initiation of appropriate therapy is essential to
minimize the degree of irreversible renal injury. Empiric
therapy may be begun in patients with severe disease,
particularly if either renal biopsy or interpretation of the
biopsy will be delayed.
References
1. Couser WG: Rapidly progressive glomerulonephritis:
classification, pathogenetic mechanisms and therapy. Am J
kidney dis 11:449-64,1988.
2. Lockwood CM: Anti-neutrophil cytoplasmic auto-antibodies:
the nephrologist’s perspective. J Am Soc Nephrol XVIII: 171-
4,1991.
3. Bolton WK: Treatment of crescenteric glomerulonephritis.
Nephrology 1:257-68, 1995.
4. Short AK, Esnoult VL, Lockwood CM: ANCA and anti-GBM
antibodies in RPGN. Adv Exp Med Biol 336: 441-44,1993.
5. Bolton WK, Wilkowski MJ: Treatment and prognosis of renal
and systemic vasculitis. Contrib nephrol 94:72-80,1991.
6. Bolton WK, Sturgill BC: Methyl-prednisolone therapy for
acute crescenteric rapidly progressive glomerulonephritis.
Am J Nephrol 9:368-75,1989.
7. Jayne DR, Davies MJ, Fox CJ et al: Treament of systemic
vasculitis with pooled intravenous immunoglobulin. Lancet
337:1137-39,1991.
 Approach to Acute Abdomen
Acute abdominal pain refers to previously
undiagnosed pain that arises suddenly and is
of less than 7 days (usually less than 48 hours)
duration. The causes of acute abdominal pain
are numerous and include intraperitoneal
as well as extraperitoneal disorders (fig 1).
The clinician should be able to tentatively
differentiate among causes which need urgent
surgical intervention from causes which need
to be managed non-surgically. It is essential to
remember that almost two thirds of the patients
who present with acute abdominal pain have
disorders for which surgical intervention is not
required.
Historically, diagnosis of the causes of acute
abdominal pain has been based largely on
Sudeep Khanna pattern recognition, in which an attempt is
made to match new cases to the classical
Consultant
presentations. No doubt, knowledge of these
Gastroenterologist
classic presentations is basic to successful
Department of
diagnosis, but it is crucial to remember that at
Gastroenterology
Pushpawati Singhania least one-third of patients with acute abdominal
Research Instutute for pain exhibit atypical features that render pattern
Liver recognition unreliable.
Renal and Digestive
Disease
Clinical Evaluation
New Delhi
History
Arun Kumar A patient listening to the patient’s complaint
Senior Consultant is the mainstay of history taking. The history
Gastroenterologist taking must include the mode of onset, duration,
Department of frequency, character, location, chronology,
Gastroenterologist radiation, and intensity of the pain, as well as
Pushpawati Singhania
the presence or absence of any aggravating or
Research Instutute for
Liver alleviating factors and associated symptoms.
Renal and Digestive Patients should be allowed to relate the history
Disease in their own words, and examiners should not
New Delhi suggest specific symptoms, except as a last
resort. Any questions that must be asked should
43
Vol. 5, Issue 3 & 4 April - Sept 2007
Sudeep Khanna1 and Arun Kumar2
be open-ended - for example, “What happens
when you eat?” rather than “Does eating make
the pain worse?” Leading questions should be
avoided. When a leading question must be asked,
it should be posed first as a negative question
(ie, one that calls for an answer in the negative),
since a negative answer to a question is more
likely to be honest and accurate. For example,
if peritoneal inflammation is suspected, the
question asked should be “Does coughing make
the pain better?” rather than “Does coughing
make the pain worse?” Usually a carefully
taken history is more valuable than any single
laboratory or x-ray finding and will help the
clinician to forego unnecessary investigations.
The severity of the underlying disease can be
assessed by the mode of onset of abdominal
pain. A sudden onset pain suggests an intra-
abdominal catastrophe, such as a ruptured
abdominal aortic aneurysm (AAA), a perforated
viscus, or a ruptured ectopic pregnancy. Rapidly
progressive pain that becomes intensely centered
in a well-defined area within a period of a few
minutes to an hour or two suggests a condition
such as acute cholecystitis or pancreatitis. Pain
that has a gradual onset over several hours,
usually beginning as slight or vague discomfort
and slowly progressing to steady and more
localized pain; suggests a subacute process and
is characteristic of peritoneal inflammation.
Numerous disorders may be associated with this
mode of onset, including acute appendicitis,
diverticulitis, pelvic inflammatory disease
(PID), and intestinal obstruction.
Pain can be either intermittent or continuous.
Intermittent or cramp-like pain (colic) is pain
that occurs for a short period (a few minutes),
followed by longer periods (a few minutes to
one-half hour) of complete remission during
which there is no pain at all. Intermittent pain is
characteristic of obstruction of a hollow viscus
and results from vigorous peristalsis in the wall
of the viscus proximal to the site of obstruction.
This pain is perceived as deep in the abdomen
and is poorly localized. The patient is restless,
may writhe about incessantly in an effort to
find a comfortable position, and often presses
on the abdominal wall in an attempt to alleviate
the pain. The intermittent pain associated with
intestinal obstruction (typically described as
gripping and mounting) is usually severe but
bearable, the pain associated with obstruction
of small conduits (eg, the biliary tract, the
ureters, and the uterine tubes) often becomes
unbearable. Obstruction of the gallbladder
or bile ducts gives rise to a type of pain often
referred to as biliary colic; however, this term is a misnomer,
in that biliary pain is usually constant because of the lack of
a strong muscular coat in the biliary tree and the absence of
regular peristalsis. Continuous or constant pain is pain that is
present for hours or days without any period of complete relief;
it is more common than intermittent pain. Continuous pain is
usually indicative of peritoneal inflammation or ischemia.
Certain types of pain are generally held to be characteristic of
certain diseases – for example, the general burning pain of a
perforated gastric ulcer, the tearing pain of a dissecting aneurysm,
and the gripping pain of intestinal obstruction. Remember that
the character of the pain is not always a reliable clue to its
cause.
The location of abdominal pain is only a rough guide to
diagnosis. Nevertheless in most disorders, the pain tends to occur
in characteristic locations, such as the right upper quadrant
(cholecystitis), the right lower quadrant (appendicitis), the
epigastrium (pancreatitis), or the left lower quadrant (sigmoid
diverticulitis). It is important to determine the location of the
pain at onset because this may differ from the location at the time
of presentation (so-called shifting pain). This may also give clue
to the diagnosis. For example, the classic pain of appendicitis
begins in the periumbilical region and settles in the right lower
quadrant. A similar shift in location can occur when escaping
gastroduodenal contents from a perforated ulcer pool in the right
lower quadrant. Also in patients with pancreatitis the pain may
start from epigastrium and get localized to the back. Radiation of
the pain should be taken into account. For example, biliary pain
is referred to the right subscapular area, and the boring pain of
pancreatitis typically radiates straight through to the back.
The intensity or severity of the pain is related to the magnitude of
the underlying insult. There appears to be a significant individual
difference to the perception of pain and this should be borne in
mind by the clinician. Pain that is intense enough to awaken
the patient from sleep usually indicates a significant underlying
organic cause. Past episodes of pain and factors that aggravate
or relieve the pain often provide useful diagnostic clues. For
example, pain caused by peritonitis tends to be exacerbated by
motion, deep breathing, coughing, or sneezing, and patients with
peritonitis tend to lie quietly in bed and avoid any movement.
The typical pain of acute pancreatitis is exacerbated by lying
down and relieved by sitting up. Pain that is relieved by eating or
taking antacids suggests duodenal ulcer disease, whereas diffuse
abdominal pain that appears 30 minutes to 1 hour after meals
suggests intestinal angina.
Associated gastrointestinal symptoms, such as nausea,
vomiting, anorexia, diarrhea, and constipation, often accompany
abdominal pain; however, these symptoms are nonspecific and
therefore may not be of great value in the differential diagnosis.
Vomiting in particular is common: when sufficiently stimulated
by pain impulses traveling via secondary visceral afferent fibers,
the medullary vomiting centers activate efferent fibers and
cause reflex vomiting. Once again, the chronology of events
is important, in that pain often precedes vomiting in patients
with conditions necessitating operation, whereas the opposite
is usually the case in patients with medical conditions. This is
particularly true for patients with acute appendicitis, in whom
pain almost always precedes vomiting by several hours. Diarrhea
is characteristic of gastroenteritis but may also accompany
incomplete intestinal obstruction. More significant is a history
of obstipation, because if it can be definitely established that a
patient with acute abdominal pain has not passed gas or stool
for 24 to 48 hours, it is certain that some degree of intestinal
44
Vol. 5, Issue 3 & 4 April - Sept 2007
obstruction is present. Other associated symptoms that should
be noted include jaundice, melena, hematochezia, hematemesis,
and hematuria. These symptoms are much more specific than
the ones just discussed and can be extremely valuable in the
differential diagnosis. Presence of fever suggests an inflammatory
process; however, it is usually low grade and often absent
altogether, particularly in elderly and immunocompromised
patients. The combination of a high fever with chills and rigors
indicates bacteremia, and concomitant changes in mental status
(eg, agitation, disorientation, and lethargy) suggest impending
septic shock.
Eliciting history of trauma, even if the patient thinks it to be
trivial, is mandatory. With female patients, it is essential to
obtain a detailed gynecologic history that includes the timing of
symptoms within the menstrual cycle, the date of the last menses,
previous and current use of contraception, any abnormal vaginal
bleeding or discharge, an obstetric history, and any risk factors
for ectopic pregnancy (eg, PID, use of an intrauterine device, or
previous ectopic or tubal surgery).
A complete history of previous medical conditions must be
obtained because associated diseases of the cardiac, pulmonary,
and renal systems may give rise to acute abdominal symptoms
and may also significantly affect the morbidity and mortality
associated with surgical intervention. Weight changes, past
illnesses, recent travel, environmental exposure to toxins
or infectious agents, and medications used should also be
investigated. A history of previous abdominal operations should
be obtained. A careful family history is important for detection
of hereditary disorders that may cause acute abdominal pain.
A detailed social history should also be obtained that includes
tobacco, alcohol, or illicit drug use as well as a sexual history.
Tentative Differential Diagnosis
In majority of cases, a tentative differential diagnosis should be
formed and then physical examination should be carried out.
The most common diagnosis in patients with acute abdominal
pain is nonspecific abdominal pain (NSAP) which per se is a
retrospective diagnosis of exclusion in which no cause for the
pain can be identified. Nonspecific abdominal pain accounts for
more than 34% of all patients seen. The most common surgical
diagnosis is acute appendicitis, followed by acute cholecystitis,
small bowel obstruction, and gynecologic disorders. Relatively
few patients have perforated peptic ulcer, a finding that confirms
the recent downward trend in the incidence of this condition.
One should keep in mind that the prevalence of diseases is likely
to vary among various age groups.
Physical Examination
The amount of information that can be obtained from physical
examination is directly proportional to the gentleness and
thoroughness of the examiner. The physical examination begins
with a brief but thorough evaluation of the patient’s general
appearance and ability to answer questions. The degree of
obvious pain should be estimated. The patient’s position in bed
should be noted: as an example, a patient who lies motionless
with flexed hips and knees is more likely to have generalized
peritonitis, whereas a restless patient who writhes about in bed
is more likely to have colicky pain, which suggests different
diagnoses. The area of maximal pain should be identified before
the physical examination is begun. The examiner can easily do
this by simply asking the patient to cough and then to point with
one finger to the area of maximal pain. This allows the examiner
to avoid the area in the early stages of the examination and to
confirm it at a later stage without causing the patient unnecessary
discomfort in the meantime.
A complete physical examination should be performed and
extra-abdominal causes of pain and signs of systemic illness
should be sought before attention is directed to the patient’s
abdomen. Systemic signs of shock, such as diaphoresis, pallor,
hypothermia, tachypnea, tachycardia with orthostasis, and
frank hypotension, usually accompany a rapidly progressive or
advanced intra-abdominal condition and, in the absence of extra-
abdominal causes is an indication for immediate laparotomy.
The absence of any alteration in vital signs, however, does not
necessarily exclude a serious intra-abdominal process.
Patient lies in supine position. The examination should include
inspection, auscultation, percussion, and palpation of all areas
of the abdomen, the flanks, and the groin (including all hernia
orifices) in addition to rectal and genital examinations (and, in
female patients, a full gynecologic examination). A systematic
approach is crucial: an examiner who methodically follows a set
pattern of abdominal examination every time will be rewarded
more frequently than one who improvises haphazardly with each
patient. Remember, auscultation is to be done after inspection
as palpation is likely to stimulate the intestines and give false
impression about bowel sounds.
The first step in the abdominal examination is careful inspection
of the anterior and posterior abdominal walls, the flanks,
the perineum, and the genitalia for previous surgical scars
(possible adhesions), hernias (incarceration or strangulation),
distention (intestinal obstruction), obvious masses (distended
gall bladder, abscesses, or tumors), ecchymosis (trauma,
pancreatitis) or abrasions (trauma), striae (pregnancy or ascites),
everted umbilicus (increased intra-abdominal pressure), visible
pulsations (aneurysm), visible peristalsis (obstruction), limitation
of movement of the abdominal wall with ventilatory movements
(peritonitis), or engorged veins (portal hypertension).
The next step in the abdominal examination is auscultation. In
general the absence of bowel sounds indicates a paralytic ileus;
hyperactive or hypoactive bowel sounds often are variations of
normal activity; and high-pitched bowel sounds with splashes,
tinkles (echoing as in a large cavern), or rushes (prolonged, loud
gurgles) indicate mechanical bowel obstruction.
The third step is percussion to search for any areas of dullness,
fluid collections, sections of gas-filled bowel, or pockets of
free air under the abdominal wall. Tympany may be present in
patients with bowel obstruction or hollow viscus perforation.
Percussion can be useful as a way of estimating organ
size and of determining the presence of ascites (signaled by a fluid
wave or shifting dullness). It is most useful, however, as a means
of demonstrating peritoneal irritation (rebound tenderness). The
customary technique is to dig the fingers deep into the patient’s
abdomen and then let go abruptly. This technique is a time-
honored one, but it is painful and often misleads the examiner
into assuming that an acute process is present when none exists.
Gentle percussion over the four quadrants of the abdomen is
much better tolerated by the patient; in addition, it is much more
accurate in demonstrating rebound tenderness.
The last step, palpation, is the most informative aspect of the
physical examination. Palpation of the abdomen must be
done very gently to avoid causing additional pain early in the
examination. It should begin as far as possible from the area of
maximal pain and then should gradually advance toward this
area, which should be the last to be palpated. The examiner
should place the entire hand on the patient’s abdomen with
the fingers together and extended, applying pressure with the
45
Vol. 5, Issue 3 & 4 April - Sept 2007
pulps (not the tips) of the fingers by flexing the wrists and the
metacarpophalangeal joints. It is essential to determine whether
true involuntary muscle guarding (muscle spasm) is present.
This determination is made by means of gentle palpation over
the abdominal wall while the patient takes a long, deep breath.
If guarding is voluntary, the underlying muscle immediately
relaxes under the gentle pressure of the palpating hand. If,
however, the patient has true involuntary guarding, the muscle
remains in spasm (ie, taut and rigid) throughout the respiratory
cycle (so-called boardlike abdomen). True involuntary guarding
is indicative of localized or generalized peritonitis. It must be
remembered that muscle rigidity is relative: for example, muscle
guarding may be less pronounced or absent in debilitated and
elderly patients who have poor abdominal musculature. In
addition, the evaluation of muscle guarding is dependent on the
patient’s cooperation.
Palpation is also useful for determining the extent and severity
of the patient’s tenderness. Diffuse tenderness indicates
generalized peritoneal inflammation. Mild diffuse tenderness
without guarding usually indicates gastroenteritis or some
other inflammatory intestinal process without peritoneal
inflammation. Localized tenderness suggests an early stage of
disease with limited peritoneal inflammation.
Careful palpation can elicit several specific signs - such as
the Rovsing sign (associated with acute appendicitis) and the
Murphy sign (acute cholecystitis) - that are indicative of localized
peritoneal inflammation. Similarly, specific maneuvers can
elicit signs of localized peritoneal irritation, such as the psoas
sign (associated with retrocecal appendicitis), the obturator
sign (pelvic appendicitis), and the Kehr sign (diaphragmatic
irritation). One very important maneuver is the Carnett test,
in which the patient elevates his or her head off the bed, thus
tensing the abdominal muscles. Tenderness to palpation persists
when the pain is caused by abdominal wall conditions (eg, rectal
sheath hematoma) but decreases or disappears when the pain is
caused by intraperitoneal conditions (the Carnett sign).
Rectal, genital, and (in women) pelvic examinations are an essential
part of the evaluation in all patients with acute abdominal pain.
The rectal examination should include evaluation of sphincter
tone, tenderness (localized versus diffuse), and prostate size and
tenderness, as well as a search for the presence of hemorrhoids,
masses, fecal impaction, foreign bodies, and gross or occult blood.
The genital examination should search for adenopathy, masses,
discoloration, edema, and crepitus. The pelvic examination in
women should check for vaginal discharge or bleeding, cervical
discharge or bleeding, cervical mobility and tenderness, uterine
tenderness, uterine size, and adnexal tenderness or masses.
Although a carefully performed pelvic examination can be
invaluable in differentiating non-surgical conditions (eg, PID)
from conditions necessitating prompt operation (eg, acute
appendicitis), the possibility that a surgical condition is present
should not be prematurely dismissed solely on the basis of a
finding of tenderness on pelvic or rectal examination.
Basic Investigative Studies
Investigative studies do not substitute for clinical history taking
and good physical examination. They are useful to confirm the
diagnosis and managing the patient.
Laboratory Tests
A complete blood count, blood chemistries, and a urinalysis
are routinely obtained unless the patient is extremely
hemodynamically unstable. The hematocrit is important in that
it allows the detection of significant changes in plasma volume
(eg, dehydration caused by vomiting, diarrhea, or fluid loss into
the peritoneum or the intestinal lumen), preexisting anemia,
or bleeding. An elevated white blood cell count is indicative of
an inflammatory process and is a particularly helpful finding
if associated with a marked left shift; however, the presence
or absence of leukocytosis should never be the single deciding
factor as to whether the patient should undergo an operation. A
low white blood cell count may be a feature of viral infections,
gastroenteritis, or NSAP.
Serum electrolyte, blood urea nitrogen, and creatinine
concentrations are useful in determining the nature and extent of
fluid losses. Blood glucose and other blood chemistries may also
be helpful. Liver function tests are mandatory when abdominal
pain is suspected to be hepatobiliary in origin. Similarly, amylase
and lipase determinations are mandatory when pancreatitis is
suspected, although it must be remembered that amylase levels
may be low or normal in patients with pancreatitis and may be
markedly elevated in patients with other conditions (eg, intestinal
obstruction, mesenteric thrombosis, and perforated ulcer).
Urinalysis may reveal red blood cells (suggestive of renal or
ureteral calculi), white blood cells (urinary tract infection or
inflammatory processes adjacent to the ureters, such as retrocecal
appendicitis), increased specific gravity (dehydration), glucose,
ketones (diabetes), or bilirubin (hepatitis). A pregnancy test
should be considered in any woman of childbearing age with
acute abdominal pain.
Imaging
In patients with acute abdominal pain, initial radiologic
evaluation includes plain films of the abdomen in the supine and
standing positions and chest radiographs. If the patient is unable
to stand, a left lateral decubitus radiograph should be obtained.
The plain radiographs may help confirm diagnoses suggested by
the history and the physical examination, such as pneumonia
(signaled by pulmonary infiltrates); intestinal obstruction (air-
fluid levels and dilated loops of bowel); intestinal perforation
(pneumoperitoneum); biliary, renal, or ureteral calculi (abnormal
calcifications); appendicitis (fecalith); incarcerated hernia (bowel
protruding beyond the confines of the peritoneal cavity);
mesenteric infarction (air in the portal vein); chronic pancreatitis
(pancreatic calcifications); acute pancreatitis (the so-called colon
cutoff sign); visceral aneurysms (calcified rim); retroperitoneal
hematoma or abscess (obliteration of the psoas shadow); and
ischemic colitis (so-called thumb printing on the colonic wall).
USG and CECT can help confirm the diagnosis or at times pick
up diagnosis that might not have been thought of clinically.
Remember, USG is an operator dependent process and if the
ultrasonologist reports a normal USG when the clinical suspicion
of an intra-abdominal pathology is high, get a CECT done.
An electrocardiogram is mandatory in elderly patients and
in patients with a history of atherosclerotic heart disease.
Abdominal pain may be a manifestation of myocardial disease,
and the physiologic stress of acute abdominal pain can increase
myocardial oxygen demands and induce ischemia in patients
with coronary artery disease.
Management
After a working diagnosis has been established the course of
management follows four basic pathways depending on whether
the patient (1) is in need of immediate laparotomy, (2) is believed
to have an underlying surgical condition, (3) has an uncertain
diagnosis, or (4) is believed to have an underlying non-surgical
condition.
46
Vol. 5, Issue 3 & 4 April - Sept 2007
It must be emphasized that the patient must be constantly
reevaluated (preferably by the same examiner) even after the
working diagnosis has been established. If the patient does not
respond to treatment as expected, the working diagnosis must be
reassessed and the possibility that another condition exists must
be immediately entertained and investigated by returning to the
differential diagnosis list.
Acute Abdominal Crisis
A systematic approach to patients with acute abdominal pain
is essential because in some patients, action must be taken
immediately and there is not enough time for an exhaustive
evaluation. As outlined (see above), such an approach should
include a brief initial assessment, a complete clinical history,
a thorough physical examination, and basic laboratory and
radiologic studies. These steps can usually be completed in
less than 1 hour and should be insisted on in the evaluation
of most patients.
Indications for Immediate Laparotomy
Among the most common of the abdominal catastrophes that
necessitate immediate operation are ruptured AAAs or visceral
aneurysms, ruptured ectopic pregnancies, and spontaneous
hepatic or splenic ruptures. The relative rarity of such conditions
notwithstanding, it must always be remembered that patients
with acute abdominal pain may have a progressive underlying
intra-abdominal disorder causing the acute pain and that
unnecessary delay in diagnosis and treatment can adversely
affect outcome, often with catastrophic consequences.
When immediate operation is not called for, the physician
must decide whether urgent or non-urgent but early operation
is necessary, whether additional tests are required before a
decision can be made, whether the patient should be admitted
to the hospital for careful observation, or whether non-surgical
treatment is indicated.
Suspected Surgical Abdomen
Indications for Urgent Laparotomy or Laparoscopy
Once a definitive diagnosis has been made, it is easy to decide
whether a patient should undergo operation. On occasion,
however, a patient must be operated on before a precise diagnosis
is reached. Urgent laparotomy implies operation within 1 to 2
hours of the patient’s arrival; thus, there is usually sufficient
time for adequate resuscitation, with proper rehydration and
restoration of vital organ function, before the procedure.
Involuntary guarding or rigidity during the physical examination,
particularly if spreading, is a strong indication for urgent
laparotomy. Other indications include increasing severe localized
tenderness, progressive tense distention, physical signs of sepsis
(eg, high fever, tachycardia, hypotension, and mental-status
changes), and physical signs of ischemia (eg, fever and
tachycardia). Basic laboratory and radiologic indications for
urgent laparotomy include pneumoperitoneum, massive or
progressive intestinal distention, signs of sepsis (eg, marked or
rising leukocytosis, increasing glucose intolerance, and acidosis),
and signs of continued hemorrhage (eg, a falling hematocrit).
Additional findings that constitute indications for urgent
laparotomy include free extravasation of radiologic contrast
material, mesenteric occlusion on angiography, endoscopically
uncontrollable bleeding, and positive results from peritoneal
lavage (ie, the presence of blood, pus, bile, urine, or gastrointestinal
contents). Acute appendicitis, perforated hollow viscera, and
strangulated hernias are examples of common conditions that
necessitate urgent laparotomy.
Diagnostic and therapeutic laproscopy has come of age.
Laproscopic cholecystectomy, appendectomy, treatment for
perforated peptic ulcer,strangulated hernias has resulted in
shorter operating times, less postoperative pain, fewer chest
complications, shorter postoperative hospital stays, and earlier
return to normal daily activities than the former.
Hospitalization and Active Observation
After the initial assessment has been completed, narcotic
analgesia for pain relief should not be withheld. In appropriately
titrated doses, analgesics neither obscure important physical
findings nor mask their subsequent development. In fact, some
physical signs may be more easily identified after adequate pain
relief. Severe pain that persists in spite of adequate doses of
narcotics suggests a serious condition that is likely to call for
operative intervention.
Active observation allows the clinician to identify most of the
patients whose acute abdominal pain is caused by NSAP or
various specific non-surgical conditions. It must be emphasized
that active observation means something more than simply
admitting the patient to the hospital: it implies an active process
of thoughtful, discriminating, and meticulous reevaluation
of the patient (preferably by the same examiner) at intervals
ranging from minutes to a few hours, to be complemented by
appropriately timed additional investigative studies.
Additional investigative studies beyond the basic ones already
mentioned should be obtained only if the results are likely to
alter or improve patient management significantly. Furthermore,
the invasiveness, morbidity, and cost-effectiveness of each
additional test must be carefully weighed. More liberal use of
supplemental studies is justified in those patients in whom
the history and physical findings tend to be less reliable
(eg, the very young, the elderly, the critically ill, or the
immunocompromised).
Supplemental studies that may be considered include computed
tomography, ultrasonography, diagnostic peritoneal lavage,
radionuclide imaging, angiography, magnetic resonance
imaging, gastrointestinal endoscopy, and diagnostic laparoscopy.
Diagnostic laparoscopy has been recommended when surgical
disease is suspected but its probability is not high enough to
warrant open laparotomy. It is particularly valuable in young
women of childbearing age, in whom gynecologic disorders
frequently mimic acute appendicitis. Diagnostic laparoscopy
has also been shown to be useful in the assessment of acute
abdominal pain in ICU patients and patients with AIDS.
Indications for Early or Elective Laparotomy or Laparoscopy
Early laparotomy or laparoscopy (within 24 to 48 hours of the
initial evaluation) is reserved for patients whose conditions are
not likely to become life threatening if operation is delayed to
permit further resuscitation or additional investigative studies.
It is often possible to perform early laparotomy or laparoscopy in
patients with uncomplicated acute cholecystitis or diverticulitis
and those with nonstrangulated incarcerated hernias, thereby
preventing the increased patient risk that always accompanies
unplanned emergency operations as well as avoiding the
logistical impediments to unscheduled surgical procedures in
the middle of the night or on weekends or holidays. Similarly,
patients with simple uncomplicated intestinal obstructions often
benefit from several hours of nasogastric tube decompression
and fluid and electrolyte resuscitation.
Elective laparotomy or laparoscopy is reserved for patients
whose condition is highly likely to respond to conservative
medical management or highly unlikely to become life
47
Vol. 5, Issue 3 & 4 April - Sept 2007
threatening during prolonged periods (several days or even
weeks) of diagnostic evaluation.
Uncertain Diagnosis
Hospitalization and Active Observation
If the diagnosis is unclear, the clinician needs to decide
whether hospitalization and active observation are necessary
or whether outpatient evaluation is an option. All patients
with acute abdominal pain and evidence of extracellular fluid
deficits, electrolyte imbalances, or sepsis must be hospitalized.
Furthermore, any patient with unexplained abdominal symptoms
whose condition has not improved within 24 hours of the initial
evaluation should be hospitalized.
Supplemental studies are often required for further evaluation
and complete workup of patients with uncertain diagnoses and
for the exclusion of many medical conditions that do not call for
operation. When the diagnosis is not obvious from the history
and the physical examination, apparent on the plain radiographs,
or suggested by the basic laboratory studies, ultrasonography
and CT, both of which are now widely available, should be
considered. CT is more useful in the early evaluation of patients
with acute abdominal pain because it is not operator dependent,
is not hampered by the presence of overlying gas (which transmits
sound waves poorly and interferes with ultrasonography), and
can be performed rapidly (a complete scan of the abdomen and
pelvis takes less than 15 minutes).
Suspected Non-surgical Abdomen
There are numerous disorders that cause acute abdominal
pain but do not call for surgical intervention. These non-
surgical conditions are often extremely difficult to differentiate
from surgical conditions that present with almost
indistinguishable characteristics. For example, the acute
abdominal pain of lead poisoning or acute porphyria is
difficult to differentiate from the intermittent pain of intestinal
obstruction, in that marked hyperperistalsis is the hallmark of
both. The pain of acute hypolipoproteinemia may be
accompanied by pancreatitis, which, if not recognized, can
lead to unnecessary laparotomy. Similarly, acute and
prostrating abdominal pain accompanied by rigidity of the
abdominal wall and a low hematocrit may lead to unnecessary
urgent laparotomy in patients with sickle cell anemia crises.
To further complicate the clinical picture, cholelithiasis is also
often found in patients with sickle cell anemia.
In addition to numerous extraperitoneal disorders, non-surgical
causes of acute abdominal pain include a wide variety of
intraperitoneal disorders, such as acute gastroenteritis (from
enteric bacterial, viral, parasitic, or fungal infection), acute
gastritis, acute duodenitis, hepatitis, mesenteric adenitis,
salpingitis, Fitz-Hugh-Curtis syndrome, mittelschmerz,
ovarian cyst, endometritis, endometriosis, threatened abortion,
spontaneous bacterial peritonitis, and tuberculous peritonitis.
Acute abdominal pain in immunosuppressed patients or patients
with AIDS is now encountered with increasing frequency and can
be caused by a number of unusual conditions (eg, cytomegalovirus
enterocolitis, opportunistic infections, lymphoma, and Kaposi
sarcoma) as well as by the more usual ones.
Further Reading
R. Scott James: Acute Abdomen. In: Textbook of Surgery: The
biological basis of modern surgical practice. Ed. Courtney M.
Townsend, Jr. Sixteenth edition, 2001. Harcourt Asia Pte. Ltd.

Dr Vijay Agarwal
Executive Director
Pushpanjali Crosslay
Hospital
Vol. 5, Issue 3 & 4 April - Sept 2007
Maintaining Quality in
Healthcare Services
With the emerging changes in the access to
health care information and the consequent
increase in consumer expectations, the need
to formalize the definition of “Quality of care”
is strongly felt.
A definition of quality, developed in 1990, has
been widely accepted and is still robust today:
“Quality of care is the degree to which health
services for individuals and populations
increase the likelihood of desired health
outcomes and are consistent with current
professional knowledge.”
Several ideas in the definition
deserve elaboration:
Health services refer to a wide array of
services that affect health, including those for
physical and mental illnesses. It includes
services aimed at preventing disease and
promoting health and well-being as well as
acute, long-term, rehabilitative, and palliative
care. Furthermore, the definition applies to
many types of health care practitioners (eg,
physicians, nurses, various other health care
professionals) and to all settings of care (from
hospitals and nursing homes to physicians’
offices, community sites, and even private
homes).
Individuals and populations draw attention
to the different perspectives that need to be
addressed. On one hand, we are concerned
with the quality of care that individual health
plans and clinicians deliver to individuals in
specific episodes of care. On the other hand,
we must direct attention to the quality of care
across the entire system. In particular, we
must ask whether all parts of the population
have access to needed and appropriate
services and whether their health status is
improving.
Desired health outcomes refers to health
outcomes that patients desire and highlights
the crucial link between how care is provided
and its effects on health, as well as the need
to ensure that patients and their families are
well informed about alternative health care
interventions and their expected outcomes. It
underscores the importance of being mindful
of people’s ability to function as well as
possible in their daily lives in addition to
attending to more narrowly defined medical
outcomes of disease. It also includes a
consideration of patient and family satisfaction
with health care services.
49
Dr. Vijay Agarwal
Increases the likelihood of beneficial outcomes
reminds us that quality is not identical to
positive outcomes. Poor outcomes occur
despite the best possible health care because
disease often defeats our best efforts.
Conversely, patients may do well despite poor
quality care because humans are resilient.
Assessing quality thus requires attention to
both processes and outcomes of care.
Current professional knowledge emphasizes
that health care professionals must stay abreast
of the dynamic knowledge base in their
professions and use that knowledge
appropriately.
This definition points to the need to create
reliable and valid measures with which to
assess the quality of health care over a wide
range of diagnostic and therapeutic services
and for a broad array of health and medical
problems. As the acceptance of these measures
has increased, so has the audience for them.
With this wider attention has come the need
to broaden the domain of measures to include
outcomes as well as processes of care and to
speak to the concerns of consumers by
developing outcome measures that go beyond
immediate morbidity and mortality to include
various kinds of functional status.
In general, either processes or outcomes may
be valid measures of quality. For an outcome
to be a valid measure, it must be closely
related to processes of care that can be
modified to affect the outcome.
Why Quality
Poor quality care leads to sicker patients, more
disabilities, higher costs, and lower confidence
in the health care industry. Furthermore,
consumers of healthcare services have certain
rights and expectations regarding the quality
of health services they receive, and their
perspective is very important since satisfied
clients are more likely to comply and continue
using the health care services.
In the provision of “Quality services”
Quality can be defined in a few words - Doing
the right thing, right away, and not doing the
wrong things.
1. Quality Assurance is to ensure that
activities are carried out as per
standards and to monitor and improve
performance so that the care provided
is as effective, efficient, timely and as
safe as possible.
 2. Accreditation is an assessment used by health care
organizations to accurately assess their level of
performance in relation to established standards and to
implement ways to continually improve.
Guidelines for Establishing a Quality Assurance Program
3. Ensuring quality care is the primary goal. To achieve
this goal, the hospital should:
4. Define the qualifications of physicians performing the
procedures and the facilities that are required for safe
diagnostic and interventional procedures.
5. Identify important aspects of care, defining acceptable
standards for each of these areas, and designing a
system to monitor and evaluate the care given.
6. The program must be based on objective criteria that
can define quality care and these criteria must be
applied to all individuals with the defined privileges
within an institution.
Essential Steps in Monitoring and Evaluation
There are ten steps needed in designing a program. There are:
7. Assign responsibility for the Monitoring and Evaluation
(M&E) Program e.g. For Coronary Angiography a senior
Radiologist who is knowledgeable but who does not
perform the procedure should monitor and report to
the head of the department/relevant authority.
8. Delineate the scope of the care provided e.g.
Visualization of all Coronary vessels and their
ramifications in the angiogram.
With Best Compliments From
AT THE FORE FRONT
OF UROLOGY
CIPLA INTRODUCES IN
URINARY STONES
STON1
(Potassium citrate & Magnesium Citrate Oral Solution)
50
Vol. 5, Issue 3 & 4 April - Sept 2007
9. Identify important aspects of care e.g. successful
cannulation, satisfactory results and no complications.
10. Identify indicators related to the important aspects of
care e.g. unsuccessful cannulation, unsatisfactory
results and complications.
11. Establish the thresholds for evaluation related to the
indicators e.g. unexplained indicators as determined
from procedure and clinical notes.
12. Collect and organize data.
13. Evaluate care when thresholds are reached e.g.
Scrutinize the adverse outcome.
14. Take action to resolve identified problems e.g. If the
same physician has recurrent problem consider
remedial action.
15. Determine whether care or service has improved and
document improvement.
16. Communicate relevant information to the facility-wide
Quality Assurance Program.
The program may be used as out-lined or modified to meet the
needs of the individual institution. While it monitors several
areas of practice, other areas may be added using the same
format. The complication and technical success rates are based
on literature data.
Whose responsibility?
The Chairman of the Department is responsible for the Quality
Assurance Program for the entire department. He/she will
evaluate care and report the results to the department at the
monthly meeting. Each practitioner has the responsibility to
ensure that all the care given by him/her is properly recorded
and that any complications are reported. The nurse is
responsible for maintaining the records and complications.
Data Collection
The data source will consist of the logs of the patients. This
case log will include the patient’s name, hospital number,
physician, date indication, and the specific diagnosis.
A separate complication log will be maintained, and will
contain the patient data and a brief summary of the details of
the complication.
All records and case logs will be monitored as part of the
department’s confidential peer review file.
Evaluation
All complications will be presented by the staff physician
responsible and the circumstances of the event will be
discussed at the monthly Quality Assurance Meeting. In
addition, every six months the cumulative data will be
presented at the department meeting. Complications that
exceed the thresholds will be discussed, both for individual
staff and the department as a whole. The complications of all
physicians in the department will be monitored in the same
manner. Similarly, when the thresholds for efficacy and
appropriates are not met, a review will be done (see next
section).
Action to Improve Care
When complications are presented at the monthly meeting,
they will be classified as avoidable or unavoidable by the staff.
Means of preventing repeated avoidable complications will be
discussed and agreement will be reached.
The review done each six months will be divided into the
three areas of greatest concern: appropriateness, efficacy and
safety. When appropriateness thresholds are exceeded, either
by an individual or by the department as a whole, the specific
cases will be discussed. The indications may need to be
broadened as a result of the review of new evidence.
Alternatively, reemphasis of the consensus view for procedural
indications will occur.
When efficacy or safety thresholds are exceeded, the review
will focus on the specific cases, the general expertise of the
practitioners involved, the overall patient population served,
and the equipment related issues. A specific plan of action
will be formulated. This may involve alternation of thresholds
because of the patient population, further continuing medical
education courses for some practitioners or voluntary limitation
of privileges. The plan will be implemented by the chief of the
department, and he/she will monitor the results of the actions
taken.
Where there is repeated or gross failure of an individual to
meet the standards outlined by the department, and there is
not sufficient improvement after the above actions, following
the hospital’s medical staff by laws and procedures, involuntary
limitations of privileges may be considered.
Follow-up of Actions Taken
The Problem area will be reviewed at subsequent meetings,
after action has been taken. The chief of the department will
51
Vol. 5, Issue 3 & 4 April - Sept 2007
report each 6 months until the thresholds are no longer
exceeded. This report will be recorded in the department’s QA
meeting minutes.
Reporting
As defined in the institutional quality assurance plan, the
results of the department meetings will be reported to the
Hospital Quality Assurance Committee. The specific actions
taken will be included, as will the results of previous actions.
If there are any specific recommendations for altering the
hospital privileges of any of the medical staff, based on the
accumulated data, these will be presented.
Tenets of Change
Total Quality Management (TQM) can be successful only if
there is buy-in from those in a position of leadership. Leaders
must be educated in the concepts of TQM and make that
education available to everyone in the organization. Leaders
must be aware that their roles will change and that their
primary responsibility will be to become the mentors and
facilitators of change. This change in role will allow them to
provide the long range planning and goal setting necessary to
success.
Participants must realize that everyone is responsible for
quality and that their input, ideas, and recognition of system
successes and deficiencies is critical. Leaders must empower
those participants working with the processes to make
changes.
The interdisciplinary nature of the system encourages close
relationships with hospitals, physicians, fire departments,
police departments, dispatch centers, and other service
providers. It is imperative that challenges and change be
viewed through the eyes of a ‘system’, which employs the
input of all of the players involved.
invites case studies, original,
and review articles on different specialties
Please sumit your contributions by email
at
pmc_pub@yahoo.co.in, pmc_pub@hotmail.com
or
by post at the address given below
Pushpanjali Medical Publications Pvt. Ltd.
A-14, Pushpanjali, Vikas Marg Extn.,
Delhi-110092
Ph: 22162818, 42427641, 22372852-58 Extn. 1602
Fax no. 011-22372851
 Pushpanjali Family Physicians Forum
(PFPF)
V. K. Malhotra

Pushpanjali Family Physicians Forum continues

to add quality strength by virtue of frequent
sessions by experts with family physicians
who are eager to upgrade and update their
information base on related progress in the
field of medical sciences.

Dr. Nandi taking his session with family physicians

Intimate discussions between Dr. Vijay Agarwal and
family physicians A team of senior Anesthetists & Intensivist,
Dr Alok Basu Roy, Dr Atul Gupta and
A session with Dr Vijay Agarwal was welcome Dr Pardeep Sharma conducted a workshop on
as he spoke on Quality Redefined as far as CPR. Dr Basu made a presentatioan on CPR,
Medical Services are concerned. According to highlighting various methodologies involved
Dr Vijay, we are in the era of dealing with well in CPR and the intricacies involved depending
informed and educated customers who have a on patient condition calling for attending
certain level of expectations from the Medical physician to take certain precautions with a
fraternity and to meet such requirement/ view to benefit the patient in as little time
expectations, a family physician is supposed as possible, however Dr Basu made it a must
to provide services that are holistic in that help of dedicated facility to deal with
nature and address the overall patient needs patient is the first thing a physician must
(psychological and physiological) rather his call for before he / she starts even attending
disease only. the patient. Dr Atul Gupta and Dr Pardeep
Dr Malay Nandi, Consultant Medical Sharma gave a demonstration on CPR by
Oncologist with Fortis Hospital during his using the dummy (Resscae Anne). The CPR
presentation on Cancer and related problems workshop continued for good 2 hrs and was
was of the opinion that family physician must appreciated by all family physicians in one
play the role of a guide and counselor with voice.
his patients in advocating
the precautions essential
to avoid cancer. In view
of increasing incidence
of Head & Neck cancers
Dr. Nandi wanted family
physicians to start a crusade
in spreding the message to
refrain from tobacco and
tobacco products usage.
He gave a brief on various
symptoms that different
V. K. Malhotra types of cancer may
Head, trigger and knowing the
Department of symptoms at an early stage
Family Medicine can be of immense help to
Pushpanjali Medical
the sufferer and treating (R to L) Dr. Atul Gupta, Dr. Pradeep Sharma and Dr. Alok Basu Roy busy
Centre
Oncologist. discussing CPR

53
Vol. 5, Issue 3 & 4 April - Sept 2007
 Pushpanjali Health Care
Events and Initiatives
April 8, 2007 – Pushpanjali
Health Care organising “Vision
Pushpanjali” at indiaHabitat Centre
On the afternoon of 8th April, 2007 “Vision
Pushpanjali” was organized at India Habitat
Centre as a welcome to honorable Dr Vijay
Agarwal (Formery, Director Max Hospital) who
has come on the Board of Crosslay Remedies
Dr. Vijay Agarwal making his presentation
Limited, a Pushpanjali Group Company as
Executive Director. Gracing the occasion,
Dr Vijay introduced himself by making a
presentation on Quality Medical Practices
leading to services that are holistic in nature
and address overall patient needs. Dr Vijay
spoke on Medical Quality Assurance in line
with international standards and guidelines,
essential to the functioning of a Health care
facility. He gave an extensive presentation on
pre-requisites to NABH accreditation and the
importance of such accreditations in view of
delivering services on par with the best and
to the satisfaction of service users.
On the occasion, Dr Vinay Aggarwal Ajay Aggarwal at the helm of affairs. The two
re-emphasized the importance of quality
healthcare and appreciated Dr Vijay’s effort
in letting the audience know about the same.
Audience all ears to the presentation
He also welcomed Dr Vijay on the Board
of Directors of Crosslay Remedies Limited
engaged in the erection of 400 bedded multi
super specialty Pushpanjali Crosslay Hospital
and hoped that with Dr Vijay’s joining, the
team would be better placed in delivering
a world class facility on schedule and with
systems that were of high quality and user
friendly to both service providers and service
consumers.
54
Vol. 5, Issue 3 & 4 April - Sept 2007
May 1, 2007 – Crosslay Remedies
Ltd. open School and Dispensery
for children and the workers at
the upcoming project, Pushpanjali
Crosslay Hospital
Carrying out the mission to serve society,
Pushpanjali started a play school for the
children of construction workers at the site
Children enjoying the positive change in their routine
of upcoming Pushpanjali Crosslay Hospital.
There are more than 40 children who have
been provided with uniform, writing material
and are offered day meal. Two teachers
have been deployed to run the school while
none other than Dr. P D Garg has taken the
responsibility to manage the progress of this
h u m b l e
initiative.
A free
dispensary
has also
been set up
at the site Dr. Ajay Aggarwal attending a patient
with Dr
noble initiatives have brought a ray of hope
among the construction workers and they
are extremely happy to be taken care of ---
perhaps for the first time in their live.
May 13, 2007 – Crosslay Remedies
Ltd. celebrate Mother’s Day over
breakfast at the site of Pushpanjali
Crosslay Hospital
Mothers Day on 13 May was celebrated in
style over Breakfast at the site of Pushpanjali
Dr. Satya Gupta, R. Sahni and Dr. P.D. Garg (L to R)
discussing the project PCH
Crosslay Hospital. Attended by over 60 medical consultants
and Pushpanjali team members. Talking on the occasion, Dr
Vinay expressed his gratitude to two mothers present at the
Dr. Vinay talking about the height while Dr. Satya Jain and
Dr. P.. D. Garg appreciate the details
site, one who gave him birth (Shrimati Satya) and one who
gave him firm footing in medical field (Dr Satya). Dr Vinay’s
gesture was well applauded and appreciated.
May- June 2007 – Pushpanjali organised basic
training programe on Computer operations for
Consultants
In pursuit of continued improvement in human talent and
manpower, on the initiative of Dr Vinay Aggarwal, more than
Trainer highlighting the nuances of computer operations
30 consultants of Pushpanjali Hospitals undertook, in batches
of 5-6, a five-day crash course on basic computer operations.
A Computer class in progress
All the consultants were very happy to be offered such an
opportunity and their enthusiasm in learning the teaching
during each of the session was to be seen to be believed.
55
Vol. 5, Issue 3 & 4 April - Sept 2007
June 10, 2007 – Press Conference on Aesthetic
Surgery with Dr. Dinesh Bhargava
Aesthetic surgery is fast emerging on the medical horizon of
India, every other day the press carries out one or the other
news about various procedures either in demand or being
performed. Pushpanjali has decided to set up a “Centre of
Excellence” in Aesthetic surgery at the upcoming Pushpanjali
Crosslay Hospital. As reported in our last issue, a three-day
Dr. N. Saini (L) and Dr. Dinesh Bhargav (R) listening to Dr. Vijay Agarwal
workshop on Aesthetic surgery was organized by Pushpanjali
Hospitals and on the success of same, there has been a lot of
interest expressed by media community to know more about
our initiatives. In pursuant of the demand, on 10th june,
2007 a press conference with Dr Dinesh Bhargav, an eminent
A Press Reporter being welcomed to the Press conference
Aesthetic Surgeon from USA who is setting up the centre of
excellence and settling down with Pushpanjali was organized
at IMA Convention Centre. The press conference was well
attended by over 20 senior reporters.
July 7-8, 2007 – Ist interactive ECG Workshop
using touch pad technology
Pushpanjali Hospitals together with National Heart Institute
and IMA-East Delhi Branch under the leadership of
A presentation in progress
Dr. Vinay Aggarwal (Chairman & Managing Director, Pushpanjali
Hospitals), Dr O P Yadava (CEO & Chief Cardiothoracic
Surgeon, NHI), Dr Atul Gupta (President, IMA-East Delhi
Branch) and Dr Anil Motta (Organizing Secretary) organized
a first of its kind two-day workshop on Electrocardiography
Pushpanjali Medical Publications stall during trade exhibition at the
workshop
on 7-8 July, 2007 at IMA Convention Centre, New Delhi. The
most redeeming features of the workshop were a) Exclusive
scientific programme designed by Dr O P Yadava, b) Eminent
Dr. Vinay and Dr. Yadava welcoming the chief guest Dr. Padmavati
faculty, c) Touch pad technology, d) Very well attended by
over 200 delegates, e) Extremely interactive and f) Very well
organized.
A panoramic view of the audience enjoying the deliberations
There was overwhelming appreciation of the content and
style of the workshop by a majority of attending delegates.
A large number of pharma corporates and organizations
from associated industry including multi national banks
participated in the event. Overall the workshop was a grand
success and served the purpose it was organized for.
56
Vol. 5, Issue 3 & 4 April - Sept 2007
Dr. O.P. Yadava fine tuning a presenation while Dr. Vinay Aggarwal and
Dr. Anil Motta look on
August 22, 2007 – Press Conference on Medical
Emergencies workshop
There is a pressing need to keep doctors updated with the
emerging trends and technological advancements so that they
can efficiently handle emergency cases.
Dr. Vijay Agarwal addressing the reporters
“Therefore, the medical fraternity has to be accordingly tuned
and updated. The coming update on medical emergencies
simply aims at keeping the medical fraternity in tune with
latest advances in managing such cases,” Dr Vijay Agarwal,
Director and Advisor, Strategy & Planning, Pushpanjali Group
of Hospitals said at the press conference.
“In India, continuous medical education is still not a
structured activity. We are just making humble contributions
Delegates participating in the proceedings
to fill that void,” Dr Rajiv Gupta, the city’s leading physician
and Vice- Chairman of the workshop said.
Speaking on the occasion, Dr Atul Gupta, President, East
Delhi Branch of IMA, said that the experts in the workshop
would discuss different dimensions of medical emergencies
through case-based studies.
“The two-day workshop is a joint initiative of Pushpanjali
Group of Hospitals and East Delhi Branch of IMA,” Dr. Arvind
Narayan, Hony. Secretary IMA East Delhi Branch informed at
the press conference.
August 25- 26, 2007 – “Medical Emergencies” An
Interactive Case Based Update
Pushpanjali Medical Publications, Pushpanjali Health Care
Company organized a two-day Interactive Case Based Update
on Medical Emergencies together with IMA-East Delhi Branch
on 25-26 August, 2007 at IMA Convention Centre, New
Delhi.
Chief Gust Dr. Ajay Kumar (C) flanked by Dr. Ashok Grover,
Dr. Atul Gupta, Dr. Vinay Aggarwal, Dr. Parkash Gera, Dr. Vijay Agarwal
and Dr. Arvind Narayan (L to R)
their initiative of joining hands with Pushpanjali Health Care
for an excellent conference.
Dr Vinay speaking on the occasion thanked Dr Ajay for his
inspirational presence and encouragement, which according to
him would help Pushpanjali to further strengthen the resolve
to set an example / benchmark in health care industry for its
pioneering “Cooperative Corporate” concept.
The conference was a roaring success as more than 200
delegates from NCR Delhi and adjoining states attended the
same, while pharmaceutical and allied industry supported
whole heartedly the cause of the conference.
Books released by Pushpanjali Medical Publications entitled
“Medical Emergencies IIIrd edition”, “Pocket Book of
Poisoning” and “Baby’s Own Cook Book” did brisk business
and were a sell out from the stall put up by Pushpanjali
Medical Publications under the supervision of Ms Tabassum.
The conference based on the feedback from attending delegates
and the faculty, was an excellent job done and they were all
praise for Dr Ashok Grover, Organizing Secretary and his
team and Mr Atul Gandotra, Conference Coordinator and his
team, who played their respective roles in the best possible
manner under the overall leadership of Dr Vinay Aggarwal,
Chairman and Managing Director, Pushpanjali Health Care.

Chief Guest, Dr Ajay Kumar, President IMA, graced the release

of books and inauguration of the conference. Speaking on the
occasion, Dr Ajay extended his heartfelt congratulations to Dr
Vinay Aggarwal and Pushpanjali Medical Publications for an
excellent work related to high quality books that benefited
medical fraternity immensely and also for conducting a series
of Medical workshops to fine tune patient management skills
of clinicians. He was all praise for Dr Parkash Gera and
Dr Ashok Grover, Chairman and Organizing Secretary

A session in progress

Dr. Ashok Grover (Org. Sec.) And Dr. Parkash Gera (Chairman) watchful
on the proceedings

respectively of the conference for working out a comprehensive

scientific programme to be conducted by more than 50 elite
experts. According to Dr Ajay, organizing such a conference
is a Herculean task and calls for great amount of wisdom,
vision and courage.

Dr Ajay thanked Dr Atul Gupta, President, IMA-East Delhi

Branch and Dr Arvind Narayan, Secretary of the branch for A panaromic view of the audience

57
Vol. 5, Issue 3 & 4 April - Sept 2007
A beaming Dr. Mamta Grover (L) on the release of her Baby’s Own Cook The delegates learning the finer naunces of CPR
Book

Dr. O. P. Kalra, Dr. Sunil Parkash and Dr. N.P. Singh ( L to R) all absorbed Editors Dr. N.P. Singh and Dr. Ashok Grover together with Dr. Vinay
while the presentation is on Aggarwal and Dr. Ajay Kumar releasing Pocket Book of Posioning

Chief Gust Releasing Medical Emergencies 3rd edition together with Pushpanjali Publication team busy selling books
the editors Dr. Rajiv Gupta Dr. Ashok Grover, Dr. Vinay Aggarwal and
Dr. Parkash Gera (L to R)

Dr. Mukesh Ajmera (L) and Dr. Vinay Aggarwal assessing the scientific sessions A worm eye view of the trade exhibition at the venue
while Mr. Atul Gandotra discusses logistics with Dr. Naveen Atal

58
Vol. 5, Issue 3 & 4 April - Sept 2007
 Guidelines for Submission of Manuscripts
You are invited to contribute your articles,
case reports, clinical experiences and any
other relevant material which is for the benefit
of clinical community at large. The articles/
contribution should be sent to:
The Editor in-Chief
Dr. Vinay Aggarwal
& if possible), and the principal conclusion. It
The Editor
Dr Ashok Grover
Pushpanjali Medical Publications Pvt. Ltd.
A-14, 15, Pushpanjali, Vikas Marg Extn. with one figure and 5-8 references.
Delhi – 110092
E-Mail : pmc_pub@hotmail.com
pmc_pub@yahoo.co.in
Manuscripts can be submitted by e-mail,
but it is mandatory that photographs (if any)
should be submitted in glossy paper by post.
To maintain the uniformity the articles, authors
should follow the following pattern:
All Manuscripts submitted to Medi-Focus
should not have been published in any form
in any other publication, and become the
property of the publishers. All manuscripts
must be accompanied by the following written
statement signed by all the authors. “The
undersigned author (s) certify (ies) that the
article is original, is not under consideration
by any other journal, and has not been
previously published. All copyright ownership
of the manuscript entitled (title of article) Use the Sequential numbering system.
is hereby transferred to the publishers of
Medi-focus.”
Articles will be edited for style and grammar.
Technical jargon is to be kept to a minimum.
American spellings are used in the Journal.
Preparation of Manuscripts
Format. The manuscript must not exceed 10-
12 pages typed in double space (including 15-
20 references). Number all pages in sequence,
beginning with the title page. Submit a copy
of all elements arranged as follows:
Title Page. This should contain the title of the
manuscript (5-6 words title) the names of all
authors, and their affiliations, a short title (not
more than 20 letters to be used as running
head) and at the bottom of the page, institution
where the work has been carried out, and the
address for all correspondence and reprints,
including Fax, Phone and E-mail.
Structured Abstract. Should be a factual
condensation of the entire work with objective,
59
Vol. 5, Issue 3 & 4 April - Sept 2007
methods, results, conclusions and should
be in one para. The abstract should state
the purposes of the study or investigation,
basic procedures (selection of study subjects
or laboratory animal; Observational and
analytical methods), main findings (giving
specific data and their statistical significance,
should emphasize new and important aspects
of the study or observations.
Clinical Briefs must not exceed 1000 words
Text. Authors must consider and follow the
format : Introduction, Material and Methods,
Results, Discussion, and Conclusion (if
necessary). The matter must be written in
a manner which is easy to understand, and
should be restricted to the topic discussed.
Do not use vertical lines or underlining in the
text.
Acknowledgments should be placed as the last
element of the text before references.
Abbreviate measurements (cm, ml).
Abbreviations should be used sparingly and
must be preceded by the full form initially.
References. In citing other work, only
references consulted in the original should be
included. If it is against citation by others this
should also be stated.
Arrange the reference list in the sequence in
which the references are first cited. In the
text, references cited should be superscripted
and should appear on top of the line after the
punctuation. Responsibility for the accuracy
and completeness of references lies with the
author.
References should not exceed 15-20 in
number.
The Journal follows the Vancouver system of
references. References should be numbered
and listed consecutively in the order in which
they are first cited in the text. Tables should
be identified in the text by superior Arabic
numerals. The full list of references at the end
of the paper should include : names and initials
of all authors (unless more than 6, when only
the first 3 are given followed by et al); the
title of the paper; the journal title abbreviated
according to the style of Index Medicus; year
of publication; volume number; first and last
page numbers. References of books should give
the book title, place of publication, publisher
and year; those of multiple authorship should also include
the chapter title, first and last page numbers, and names and
initials of editors.
1. Mehta MN, Mehta JN. Serum lipids and ABO blood
groups in cord blood of neonates. Indian J Pediatr
1984; 51 : 30-43.
2. Smith GDL. Chronic Ear Disease. Edinburgh; Churchill
Livingstone, 1980 : 78-81.
3. Malhotra KC. Medicogenetic problems of Indian tribes.
In Verma IC, ed. Medical Genetics in India. Vol. 2.,
Pondicherry; Auroma Enterprises, 1978; 51-55.
Papers accepted but not yet published should be included in
the references followed by “In press”. Those in preparation,
personal communications and unpublished observations
should be referred to as such in the text only.
For more detailed information about the Vancouver
system, authors should consult “Uniform requirements for
manuscripts submitted to biomedical journals’ (Br Med
J. 1982; 284 : 1766-70).
Legends. A descriptive legend must accompany each illustration
and must define all abbreviations used therein.
Illustrations and graphs. Submit glossy black and white
photographs. The cost reproduction of colour photographs will
be borne entirely by the author. Number all illustrations with
Arabic numericals (1, 2).
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Vol. 5, Issue 3 & 4 April - Sept 2007
Tables. These must be self-explanatory. The data must be
clearly organized and should supplement and not duplicate
the text. Explanatory matter should be given as footnotes.
Statistical analyses used must be appropriate. Each table must
have a title and should be numbered with Arabic numericals
(1, 2).
Manuscript Submission Checklist
1. Three copies of manuscript in hard copy
2. Name and address of author responsible for
correspondence.
3. Structured Abstract (150-200 words) & 3-5 key words.
4. References, cited consecutively in the text.
5. Three glossy prints for illustrations.
6. Documentation of permission to reuse any previously
published material.
7. Covering letter, including statement of originality and
signifying approval of final copy by all authors.
8. Upon final acceptance of the manuscript, a CD disk
in MS Word should be submitted. The disk should be
labeled with the title of article, file name and version
used and must contain the final revised manuscript
material.