Practical Guide To Insulin Therapy in Type 2 Diabetes: January 2011

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Practical Guide To Insulin Therapy in Type 2 Diabetes
Book · January 2011
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Hussein Zanariah Mas Md

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TABLE OF CONTENTS
FOREWORD i
PREFACE ii
GUIDE OBJECTIVES iii
GUIDE WORKING COMMITTEE iv
EXTERNAL REVIEWERS v
SUMMARY OF TREATMENT ALGORITHM vi
SECTION 1 BACKGROUND 1
SECTION 2 RATIONALE FOR INSULIN THERAPY IN

TYPE 2 DIABETES 4
SECTION 3 BARRIERS TO INSULIN THERAPY 10
SECTION 4 INSULIN TYPES AND REGIMENS 15

4.1 Insulin types
4.2 Insulin analogues
4.3 Insulin regimens
SECTION 5 INSULIN INITIATION AND OPTIMISATION

(DOSE ADJUSTMENT) 22
5.1 Initiating and optimising with basal insulin
5.2 Initiating and optimising with premixed insulin
5.3 Initiating and optimising with prandial insulin
5.4 Initiating and optimising with basal and
prandial insulin
SECTION 6 INSULIN INTENSIFICATION

(SWITCHING INSULIN REGIMENS) 31
6.1 Switching from basal to basal plus regimen
6.2 Switching from basal to basal bolus regimen
6.3 Switching from basal to premixed regimen
6.4 Switching from premixed to basal bolus regimen
6.5 Switching from single to multiple premixed regimen
6.6 Intensification of premixed regimen with addition
of pre-meal bolus
6.7 Intensification of prandial regimen with addition
of basal insulin
TABLE OF CONTENTS
SECTION 7 TARGETS AND MONITORING 42

7.1 Glycemic targets
7.2 Monitoring insulin therapy
SECTION 8 PROBLEMS WITH INSULIN THERAPY 48

8.1 Hypoglycemia
8.2 Weight gain
8.3 Injection site problems
8.4 Insulin allergy and hypersensitivity
SECTION 9 SPECIAL SITUATIONS 55

9.1 Sick days
9.2 Travel
9.3 Exercise
9.4 Fasting (Ramadan)
9.5 Pregnancy
SECTION 10 PRACTICAL ISSUES 64

10.1 Insulin handling and storage
10.2 Insulin injection sites
10.3 Insulin pen devices
10.4 Insulin absorption
10.5 Insulin injection problems
10.6 Self Monitoring of Blood Glucose (SMBG)
APPENDIX Carbohydrate counting 75
INDEX 77
GLOSSARY OF TERMS 81
ACKNOWLEDGEMENTS 82
SOURCES OF FUNDING 82
i FOREWORD BY
THE DIRECTOR GENERAL OF HEALTH OF MALAYSIA.
In Malaysia, the prevalence of diabetes mellitus among adults aged 30 years and above
had risen by almost 80% in the last decade to 14.9%. This translates to one in six adult
Malaysians above 30 years with diabetes, an estimated 1.4 million in number. It is
estimated that 95% of those with diabetes in Malaysia have Type 2 Diabetes.
With increased duration of disease, oral anti-diabetic medications often lose effective
ness and consequently there is a need to add insulin to maintain glycemic control. The
use of insulin therapy among patients with Type 2 diabetes within the Ministry of Health
has continued to increase with the recognition of the need to maintain good glycaemic
control towards prevention of long-term diabetes-related complications, as recom-
mended by recent local and international diabetes guidelines. However, insulin use in
primary care, both public and private, is still generally low in Malaysia and varies across
different states in the country. This may be due to poor acceptance of insulin therapy
among patients and healthcare providers, probably due to lack of awareness, knowledge
and guidance. Diabetes-focused health education and counseling will definitely improve
awareness, acceptance and adherence to insulin therapy among patients with diabetes.
Despite the increase in insulin use, the majority of insulin-treated patients are not able
to attain and maintain satisfactory long-term glycaemic control, as seen from recent
audits. I understand that one of the main reasons is the lack of a standardised way in
initiating, optimising and intensifying insulin therapy. There is therefore an urgent need
to have a set of guidelines in place for this provision.
I would like to congratulate our MOH’s (Ministry of Health) endocrinologists who have
worked tirelessly to develop this practical guide for insulin therapy for patients with
Type 2 diabetes. I am sure this will provide simple and clear steps for all healthcare
providers to initiate insulin safely, optimise doses well and intensify insulin regimens
promptly to ensure that insulin therapy is administered in a cost effective manner in
MOH. In addition I believe this will enable more patients to achieve and maintain good
glycaemic control, with reduction of the risk of long-term complications which equally
presents a huge economic burden.
I urge all of you to make full use of this new practical guide for insulin therapy in Type
2 Diabetes, as it represents another important clinical tool for improving quality of
diabetes care in the country.
TAN SRI DATO’ SERI DR. HJ. MOHD ISMAIL MERICAN

ii PREFACE
The prevalence of diabetes in Malaysia continues to increase at an alarming rate from

1-2% in the 1960s and 1970s, 6.3% in 1986 (NHMS I), 8.2% in 1996 (NHMS II) to
14.9% in 2006 (NHMS III). More recent studies have indicated that the prevalence
has risen to beyond 20%. This is largely contributed by a parallel increase in rates of
overweight/obesity and high rates of physical inactivity among the adult population
together with population growth, aging and urbanization.
Oral anti-diabetic medications comprise the mainstay of treatment for patients with
type 2 diabetes in Malaysia. The majority of patients receiving treatment have
suboptimal glycaemic control, often as a result of treatment inertia with lack of
optimsation of oral medications and delay in insulin initiation. Insulin use in the
management of type 2 diabetes is still seriously lacking especially in primary care.
Currently insulin therapy is used in an estimated 20% of outpatients with diabetes in
the MOH Health facilities, noted from a survey done by Institute of Health Management
(IHM) in 2008. This has increased compared to 13% in a similar survey by IHM in 2005.
The increase in insulin use is expected with current treatment guidelines (CPG
Management of Type 2 DM 2009) recommending earlier use of insulin therapy in
patients with sub-optimal glycemic control either at presentation or with failure of oral
anti-diabetic agents.
Unfortunately, several local audits have shown that very few patients on insulin therapy
are able to achieve good glycaemic control, as measured by HbA1c of less than 6.5%.
Only 10 – 15% of patients on insulin therapy are able to achieve recommended glycaemic
targets. Studies have also shown that in most instances insulin is prescribed using less
intensive regimens without good optimisation of dose.
The barriers to achieving good glycaemic control include poor medication adherence,
hypoglycaemia, poor optimisation of insulin doses, lack of intensification of insulin
regimens, especially the use of more intensive insulin regimens that require more
frequent injections, the and use of both meal and basal insulin (basal bolus regimens).
In recent years, a large proportion of diabetes care in developed countries has moved
from specialist units to primary care and insulin is now frequently and successfully
initiated in the primary care setting. This change has been sponsored by government
policies and guidelines which encourage providers of primary care to initiate and
manage insulin.
This Practical Guide to Insulin Therapy has been developed to provide a clear and
concise approach to all health care providers on current concepts in the use of insulin
in the management of type 2 diabetes (T2DM). I hope it will help to address the current
shortfalls in the management of patients with T2DM requiring insulin therapy and it will
be fully utilised by all relevant health care providers, especially in primary care. Last but
not least I would like to express my gratitude to everyone involved in the development
of this practical guide and especially to the task force members for their immense
support and contribution.
Dr Zanariah Hussein
Chairperson
Working Committee
iii GUIDE OBJECTIVES
Objectives
The aim of the practical guide is to assist health care providers, particularly primary
care physicians in making key decisions to initiate, optimise and intensify insulin
management and decrease long-term morbidity risk in patients with Type 2 diabetes.
Clinical Questions
The clinical questions of these guidelines are:
1. Why is insulin therapy needed in Type 2 diabetes?
2. How to initiate insulin therapy?
3. How to optimize insulin doses?
4. How to intensify insulin regimens?
5. How to monitor glycemia in patients on insulin therapy?
6. What are the problems and practical issues related to insulin therapy?
Target Population
This practical guide is applicable to children, adolescents and adults with T2DM
Target Group
This practical guide is meant for all health care professionals involved in treating
patients with T2DM which includes medical officers, family medicine specialists,
primary care physicians, general practitioners, public health personnel, general
physicians, endocrinologists, cardiologists, nephrologists, neurologists, geriatricians,
obstetricians and gynaecologists, paediatricians, ophthalmologists, nurses, assistant
medical officers, podiatrists, pharmacists, dieticians and diabetic nurse educators.
iv GUIDE WORKING COMMITTEE
CHAIRPERSON
Dr. Zanariah Hussein

Senior Consultant Endocrinologist,
Hospital Putrajaya
Putrajaya
MEMBERS (Alphabetical Order)
Dr. Foo Siew Hui Dr. Noor Lita Adam

Consultant Endocrinologist, Consultant Endocrinologist,
Hospital Selayang Hospital Seremban
Selangor Seremban
Dr. Lim Siang Chin Dr. Nurain Mohd. Noor

Hospital Melaka Hospital Putrajaya
Melaka Putrajaya
Dr. Masni Mohamad Dr. Shamita Sharma

Hospital Putrajaya Hospital Ampang
Putrajaya Selangor
Dr. Mohamed Badrulnizam Long Bidin

Consultant Endocrinologist,
Hospital Kuala Lumpur
Kuala Lumpur
Dr. Yong Sy Liang

Consultant Endocrinologist,
Hospital Klang
Selangor
v EXTERNAL REVIEWERS
Prof. Dato’ Paduka Dr. Wan Mohamad Wan Bebakar

Hospital Universiti Sains Malaysia,
Kubang Kerian, Kelantan
Prof. Dr. Nor Azmi Kamaruddin

President
Malaysian Endocrine and Metabolic Society (MEMS)
Pusat Perubatan Universiti Kebangsaan Malaysia,
Kuala Lumpur
Dato. Dr. Santha Kumari

Senior Consultant Physician
Hospital Klang
Selangor
Dr. G. R. Letchuman Ramanathan

Senior Consultant Physician,
Hospital Taiping,
Perak
Dr. Feisul Idzwan Mustapha

Public Health Physician,
Disease Control Division,
Department of Public Health,
Ministry of Health Malaysia,
Putrajaya
Dr. Mastura Ismail

Family Medicine Specialist,
Klinik Kesihatan Ampangan,
Negeri Sembilan
(The following external reviewers provided feedback on the draft)

vi SUMMARY OF TREATMENT ALGORITHM
Newly diagnosed DM & Type 2 DM

• Symptomatic (osmotic symptoms) regardless HbA1c or FBS
• HbA1c > 10% or FPG > 13 mmol/L
Type 2 DM on maximal OADs (single/double/triple)
• HbA1c > 8%
Glycemic
abnormality?
FPG, SMBG
Normal Fasting / High Fasting / High Fasting /

prebreakfast BG prebreakfast BG prebreakfast BG
High daytime BG Normal daytime BG High daytime BG
Start Start Start Start Start

PRANDIAL BASAL PREMIXED PREMIXED BASAL
only only OD BD BOLUS
(usually TDS (bedtime) (predinner) (prebreakfast (premeals,
premeals) & predinner) bedtime)
Optimise Optimise Optimise Optimise Optimise
dose dose dose dose dose
Sequential
addition of
Add 3 prandial insulin
prandial
Add basal insulin
insulin
BASAL PLUS PREMIXED BD

(premeal and PREMIXED TDS* PLUS PRANDIAL
(premeals) (prelunch)
bedtime)
Optimise dose Optimise dose Optimise dose
BASAL BOLUS (prandial insulin at premeals, basal insulin at bedtime) Optimise dose
* refers to insulin analogues only
Note:
1. Metformin should be continued while on insulin therapy unless contraindicated or
intolerant
2. Sulphonylureas / Meglitinides should be withdrawn once prandial insulin is used
regularly with meals
3. Insulin dose should be optimized prior to switching / intensifying regimens
Section
1
BACKGROUND
Practical Guide to
Insulin Therapy in
Type 2 Diabetes Mellitus
2
BACKGROUND
In Malaysia, the Third National Health and Morbidity Survey (3rd NHMS) in
2006 showed that the prevalence of T2DM for adults aged 30 years old and
above had risen by almost 80% in the last decade to 14.9%1. In this population
survey of those with diabetes, 73.5% attended government health facilities
and 20% received treatment from private health facilities. The majority, 77%
were treated with oral anti-diabetic medications only and a mere 7% were
receiving insulin therapy at the time of the survey. The National Medicines Use
Survey (NMUS) in 2006 reported that insulin therapy contributed to only 8.2%
of overall anti-diabetic drug utilisation for the country2. These figures represent
low rates of insulin use when compared to other countries.
A nationwide audit done by the Institute of Health Management (IHM) 3, MOH in

2005 and 2008 showed that the use of insulin in MOH health facilities (primary,
secondary and tertiary) was 13% and 19% respectively, mainly prescribed in
tertiary hospitals with low use in primary and secondary care. A recent MOH
audit in primary care (NCD Diabetes Clinical Audit 2009) found that insulin use
in primary care was about 11.8% with marked differences between states. Use
of insulin therapy in tertiary care was much higher at 54%4 (DiabCare 2009) and
has doubled compared to 28% 5 (DiabCare 2003) in patients attending specialist
clinics in MOH state hospitals and academic instituitions. The NMUS also
showed that insulin use was far greater in the public sector compared to the
private sector reflecting the burden of patients seen and managed by the public
sector.
Local audits and hospital based surveys have shown that more than 80% of
patients were receiving less intensive insulin regimens. The most prescribed
regimens were the ”basal only” insulin regimen (1 injection daily) in about 39%
of patients and ”premixed” insulin regimen in 45% of patients. More intensive
regimens requiring 3 - 4 injections per day were prescribed in only 13% of
patients attending physician practice (IDMPS 2006) 6. The majority ( > 80%) of
patients on insulin did not achieve HbA1c of less than 6.5%. There are many
problems in our current practice with insulin therapy that represent barriers to
achieving good glycaemic control such as poor patient acceptance, treatment
inertia, hypoglycemia, inadequate dosing, lack of optimisation of insulin regimens,
inappropriate timing of injections, non-adherence to insulin regimens and others.
3
REFERENCES
1. The Third National Health and Morbidity Survey 2006 (NHMS III). Institute for
Public Health, National Institute of Health, Ministry of Health, Malaysia.
2. GR Letchumanan, P.K.Yap Muruga V, SP CHan, Oiyammal C, Loh KM, Ariza Z,

Emieda MH, Selva Malar, Zanariah H, M Badrulnizam. Chapter 5 Use
Antidiabetics.-Report of National Medicines Use Survey. Malaysian Statistics
on Medicine 2004 Pg 9-11. (Published April 2006).
3. Haliza AM et al. Management of patients with type 2 diabetes mellitus in

Ministry of Health hospitals and health centres. Journal of Health
Management. Vol 4 no 1/ 2008 Institute of Health Management, Malaysia.
4. Results of Diabcare(Malaysia) 2009. Novo Nordisk data on file.
5. Mafauzy M. Diabetes Control and Complications in Public Hospitals in

Malaysia. For the Diabcare-Malaysia Study Group. Med J Malaysia Vol 61
No 4 October 2006.
6. Juliana Chan et al. Multifaceted Determinants for Achieving Glycemic Control.

The International Diabetes Management Practice Study (IDMPS). Diabetes
Care 2009; (32):227-233.
Section
2
RATIONALE FOR
INSULIN THERAPY
IN T2DM
Practical Guide to
Insulin Therapy in
5
RATIONALE FOR INSULIN THERAPY
IN TYPE 2 DIABETES MELLITUS
Insulin resistance and impaired insulin secretion form the two key factors to
developing T2DM. These two factors are already present at an early stage in
those with pre-diabetes, and worsen with time. At diagnosis, as seen in the
UKPDS, pancreatic beta cell function was found to be approximately 50 % of
normal, with a decline of approximately 5% per year1. It was estimated that the
reduction in beta-cell function begins 10-12 years prior to diagnosis and
approached less than 25 % of normal function 6 years after diagnosis2.
(Figure 2.1)
Figure 2.1
Progressive Decline in
Beta-cell Function in Type 2
100
ß-Cell Function (%)
75
50
25
IGT Postprandial Type 2
Hyperglycemia Diabetes
0
-12 -10 -2 0 2 6 10 14
Years From Diagnosis
T2DM is a progressive disease characterised by worsening glycemia. There are

many reasons why beta cells continue to decline. One of the important reasons
is glucose toxicity (Figure 2.2) 3.The progressive decline in beta cell function
ultimately renders oral agents ineffective and the majority of patients with
T2DM will require exogenous insulin treatment. Besides restoring circulating
hormone levels, insulin treatment has beneficial effects on insulin sensitivity,
vascular function, dyslipidemia and biomarkers that predict vascular damage.
6
Figure 2.2
Overview of factors influencing stages from insulin resistance to progression
of T2DM
Lifestyle factors:
diet, exercise, Glucose
smoking, alcohol toxicity
Genetic and
environmental
factors cause Lipotoxicity
susceptibility
Insulin Beta cell
resistance dysfunction
Amyloid
deposition
Declining beta
Genetic cell function
factors
Progression of
type 2 diabetes
Insulin is widely accepted as the most effective treatment option available to help
people with T2DM achieve treatment targets for glycemic control. Insulin therapy
is suitable at all stages of T2DM, for all ages, and with a wide range of treatment
options and regimens. Insulin has a well documented safety profile and is generally
well tolerated in those with T2DM. The glucose lowering effects of insulin are
unmatched and no maximum dose exists. Insulin can be usefully combined with
other oral anti-diabetic agents and recently has also been shown to give
improved glycemic control when combined with the other injectable agents,
GLP-agonists or mimetics4.
Numerous randomised controlled trials and large observational studies have

shown that good glycemic control can be achieved in patients with T2DM who
are treated with insulin or insulin analogues using treatment algorithms5,6.
As most people with T2DM will ultimately require long-term insulin therapy due
to the progressive nature of the disease, it seems rational to add insulin therapy
earlier rather than later. Therefore, the Malaysian CPG on Management of T2DM
2009 recommends to initiate insulin in those newly diagnosed with HbA1c of
more than 10% or fasting blood glucose (FBS) > 13mmol/L or in those on
combination OADs who are unable to achieve target HbA1c (See Figure 2.3).
7
Figure 2.3
Treatment Algorithm for the Management of Type 2 Diabetes Mellitus
(From Management of T2DM CPG 2009)
Diagnosis of Type 2 Diabetes

All patients advised LIFESTYLE
HbA1c < 6.5% OR HbA1c 6.5 - < 8.0% HbA1c 8.0 - 10.0% HbA1c > 10.0% OR
FPG < 6 mmol/L OR OR FPG > 13 mmol/L
FPG 6 - < 10 mmol/L FPG 10 - 13mmol/L
LIFESTYLE
APPROACH* OAD MONOTHERAPY COMBINATION COMBINATION
THERAPY*** THERAPY + BASAL
Follow-up with Metformin** / PREMIXED
Metformin with
HbA1c after ORAGI / DPP-4 INSULIN THERAPY
other OAD agents
3 months Inhibitor / Glinides /
(AGI / DPP-4
SU / TZDs OR
Inhibitor / Glinides
If HbA1c ≤ 6.5%
/ Incretin Mimetic /
continue with Optimise dose of INTENSIVE
SU / TZDs) or with
Lifestyle Approach. OAD agent in the INSULIN THERAPY,
insulin
subsequent 3-6 continue
If HbA1c > 6.5% on months Optimise dose of Metformin
follow-up, consider OAD agents in the
OAD monotherapy Follow-up with subsequent 3-6
HbA1c after 3-6 months
months
Follow-up with
If HbA1c ≤ 6.5%, HbA1c after 3-6
continue therapy months
If HbA1c > 6.5%, If HbA1c ≤ 6.5%,

consider continue therapy
COMBINATION OAD If HbA1c > 6.5%,
Therapy consider addition of
INSULIN THERAPY
Footnote:
If symptomatic (weight loss, polyuria, etc) at any HbA1c and FPG level, consider
insulin therapy.
Try to achieve as near normal glycaemia without causing hypoglycaemia
* Consider metformin/AGI/other insulin sensitiser in appropriate patients
** Metformin is the preferred 1st line agent, and SU should preferably not be used
as 1st line
*** Although 3 oral agents can be used, initiation and intensification of insulin
therapy is preferred based on effectiveness and expense
8
It is important to discuss the role of insulin therapy with your patients even at the
time of diagnosis of T2DM. (Refer Table 2.1)
Table 2.1
Issues for patient discussion at time of diagnosis - role of insulin
therapy
Introduce your patient to the eventual need for insulin so that it is

not used as a punishmnent
• Type 2 DM results from insufficient insulin secretion due to beta cell

dysfunction
• Over time beta cell function continues to deteriorate resulting in

increasing blood glucose levels
• Elevated glucose levels can lead to diabetes complications, progression

of disease and deteriorating health
• Treatment of elevated blood sugars slows the gradual worsening of

health
• Insulin injections will eventually be required to replace the body’s

own insulin, control blood sugar and slow disease progression
(derived from Practical Guidance to Insulin Management – Primary Care Diabetes

4 Supplement 1 ( 2010) S43 – 56)
Short term use of insulin therapy in patients with T2DM may also be considered
in the following conditions:
• Acute illness, surgery, stress and emergencies
• Pregnancy
• Breast-feeding
• As initial therapy in T2DM with marked hyperglycemia
• Severe metabolic decompensation (eg. DKA, HHS)
9
REFERENCES
1. UKPDS Group. UKPDS 16. Overview of 6 years’ therapy of type 2 diabetes-A

progressive Disease. Diabetes 1995; 44:1249-1256.
2. Holman RR. Assessing the potential for Alpha-glucosidase Inhibitors in

Prediabetes States. Diabetes Res Clin Pract 1998;40(suppl.):S21-S25.
3. Vincent P et al. Glucolipotoxicity: Fuel Excess and Beta Cell dysfunction.

Endocrine Review, 2008.
4. Maria Tzafos et al. Glucagon-Like Peptide-1 Analog and Insulin Combination

Therapy in the management of adults with type 2 Diabetes Mellitus. The
Annals of Pharmacotherapy. 2010. 44(7); 1294-1300.
5. Ryuza Kawamori et al. IMPROVE Observational Study of Biphasic Insulin

Aspart 30/70 in Patients with Type 2 Diabetes Mellitus. Expert Rev Endocrinol
Metab. 2010; 5(4):507-516.
6. Schreiber SA et al. The long term efficacy of insulin Glargine plus oral
antidiabetic agents in a 32-month observational study of every day clinic
practice. Diabetes Technol Ther. 2008. Apr;10(2):121-127.
Section
3
BARRIERS TO
INSULIN THERAPY
Practical Guide to
Insulin Therapy in
11
BARRIERS TO INSULIN THERAPY
Insulin is the most effective drug available to achieve glycemic targets in patients
with T2DM yet there is reluctance among patients and physicians to initiate
insulin. There are many barriers to insulin treatment among health care providers
and patients.
3.1 Patient barriers
In a recent survey the International Diabetes Management Practises Study

(IDMPS), which is a global registry performed to assess the current management
practices in patients with diabetes, it was shown that one of the reasons for
patients not reaching target is fear of injection1.
Another recent global survey entitled the Global Attitudes of Patients and
Physicians in Insulin Therapy (GAPPTM), conducted specifically to assess needs
and challenges relating to insulin treatment, found that more than one in three
diabetes patients skip doses or fail to take their insulin as prescribed, on average
three times in the last month. Being too busy or simply forgetting to take the
insulin are the main reasons cited by patients missing insulin doses. Two thirds
of patients taking insulin in the study were concerned about experiencing a
hypoglycemic event in the future. Nine in 10 patients wished for less invasive
insulin regimens where insulin could be dosed less than once a day.2
It is important to address the patient’s concerns regarding insulin by enquiring

about the following prior to initiating insulin2:
• What do you need to know to consider insulin?
• What problems do you think you can encounter?
• What do you think are the benefits and the negative effects of insulin?
• What will help you to overcome the concerns?
• Are you willing to consider insulin? If not, what would cause you to consider
insulin?
As healthcare providers, it is important to identify the patient’s barriers to insulin

therapy and implement strategies to overcome or decrease these barriers as this
will assist the patient in the decision-making process to accept and adhere to
insulin therapy (Refer Table 3.1)
To provide encouragement and support for insulin use it may be useful to do the
following;
• Give your patient materials that they can use at home, such as information
sheets, patient diary, and contact information for diabetes support groups
or websites
• Involve family and friends for support
• Recommend that the patient join a local diabetes support group
• Encourage your patient to talk to someone who has been successfully treated
with insulin therapy
12
BARRIERS TO INSULIN THERAPY
Table 3.1: Barriers to insulin therapy and suggested solutions
Possible barriers Suggested solutions and issues for patient discussion
Insulin as a • Reassure your patient they have done nothing wrong

personal failure • Emphasize the pathophysiology of Type 2 DM
Diabetes progression means insulin will be needed
eventually
• Explain that starting insulin at the right time will help
with glycemic control and slow disease progression
Insulin causes • Provide information to counteract this belief

complications • Acknowledging the patients fear and informing the
and death provider’s experience is helpful
• Discuss that adding insulin does not mean health is
deteriorating; rather, it is an effective step to prevent
diabetes progression and complications
Insulin injections • Explain the benefits of using pen / injection devices

are painful • Demonstrate insulin injection technique for
subcutaneous injections with a practice pen to the
patients. Highlight sites of injection
• Let the patient try an injection test / placebo injection
Fear of • Reassure them that there are strategies to prevent,

hypoglycaemia recognize and treat hypoglycaemia and thus avoid
severe events
• Basal insulins have minimal risks
Change in lifestyle Provide information and discuss about insulin and pen.
1) Restricts • Modern injection devices (insulin pens) are
independence convenient, discreet and simple to use
2) Concern of • Insulin can fit in with daily life
injecting insulin in • Selection of insulin type and regimens with maximum
public places flexibility
Insulin is not • Inform that diabetes is an insulin-related problem

effective and the insulin used is very similar to that produced
naturally
• Offer a 3-month trial to get the patient used to the idea
• Once patients try insulin they rarely want to change,
because it is successful
Insulin causes • Consult a dietician and discuss strategies to prevent

weight gain weight gain
• Lifestyle interventions with diet and exercise continue
to be important
13
3.2 Provider barriers
Barriers to insulin therapy are also seen among health care providers. This
also leads to delayed initiation of insulin therapy3.
Some barriers are listed below:

• Lack of resources — drug costs, staff, skills
• Time constraints
• Lack of familiarity/experience
• Lack of tools/algorithm
• Efficacy concern
• Risk of severe hypoglycaemia /adverse effects on quality of life (QoL)
• Concerns about patient refusal and non-compliance
• Concerns relating to educating patients
• Excess weight gain in already overweight patients
• Too demanding for elderly patients
Convincing patients to be on insulin therapy can be challenging. Good

communication between patients and health care providers is the key to
overcoming psychological barriers to insulin therapy.
Strategies to overcome these barriers among health care providers include:
• Building knowledge, experience and confidence by continuous training and

education of health care providers
• Discuss challenging and/or successful insulin initiation cases with health care
provider peers
• Networking between diabetes educators, pharmacists and diabetes support
groups
• Providing comprehensive patient education
• Arrange for timely patient follow-up to ensure patient adherence and identify
and resolve potential difficulties and challenges
• Development and implementation of comprehensive algorithms for optimi-
sation and intensification of insulin
14
REFERENCES
1. Juliana Chan et al. Multifaceted Determinants for Achieving Glycemic Control.

The International Diabetes Management Practice Study (IDMPS). Diabetes
Care 2009; (32):227-233.
2. New Global Survey Reveals Over One in Three Patients Fail to Take Insulin
as Prescribed -Global Attitudes of Patients and Physicians in Insulin Therapy
(GAPPTM) Survey - Press Release by Newswire 21st September 2010.
3. Martha M et al. Overcoming barriers to the initiation of insulin therapy. Clinical

diabetes. Vol 25, No 1, 2007.
4. Mark Peyrot el al . Resistance to Insulin therapy among patients and providers.

Results of the cross national Diabetes, Attitude, Wishes and Needs ( DAWN)
Study. Diabetes Care. Vol 28, No 11, 2005.
Section
4
INSULIN TYPES
AND REGIMENS
Practical Guide to
Insulin Therapy in
16
INSULIN TYPES AND REGIMENS
4.1 Insulin Preparations
The insulin currently used in Malaysia is recombinant human insulin, either

directly derived from the native human insulin, i.e. regular human insulin or
structurally modified, i.e. insulin analogue. Both types of insulin are further
divided into prandial, basal and premixed insulin according to their pharmacoki-
netic profiles (Table 4.1a).
• Prandial insulin is administered pre-meal because of its short or rapid onset

of action for controlling the post-prandial glucose excursion. It is also used in
insulin pumps.
• Basal insulin is administered once or twice daily. The intermediate or
long-acting pharmacokinetic profile covers the basal insulin requirements in
between meals and overnight due to endogenous hepatic glucose production.
• Premixed insulin is biphasic insulin that incorporates the combination of
short or rapid-acting insulin with its intermediate-acting counterpart into a
single preparation to cover for both postprandial glucose excursion as well as
basal insulin needs simultaneously (Table 4.1b).
Table 4.1a Insulin Preparations available in Malaysia
Insulin
Type Conventional Analogue
Prandial Short-acting regular human insulin Rapid-acting

- Actrapid® - Novorapid® (Aspart)
- Humulin R® - Humalog® (Lispro)
- Apidra® (Glulisine)
Basal Intermediate-acting or Neutral Long-acting

Protaminated Hagedorn (NPH) - Lantus® (Glargine)
Insulin - Levemir® (Detemir)
- Insulatard®
- Humulin N®
Premixed Combination of short & Combination of rapid-acting &

intermediate-acting: protaminated analogue
30% regular insulin + 70% NPH - NovoMix® 30 (30% aspart
- Mixtard® 30 + 70% aspart protamine)
- Humulin® 30/70 - Humalog Mix® 25 (25% lispro
+ 75% lispro protamine)
17
Table 4.1b Pharmacokinetic profiles of various types of insulin1
Brand (Generic) Onset Peak (Hr) Duration Timing of

Name (Hr) insulin
a) Short-acting, regular
- Actrapid®* 30 min 1-3 8 30 mins
- Humulin R®* 30 min 2-4 6-8 before meal
b) Rapid-acting analogue 5-15 mins

- Novorapid® (Aspart)* 10-20 min 1-3 3-5 before or
- Humalog® (Lispro)* 0-15 min 1 3.5-4.5 immediately
- Apidra® (Glulisine) 5-15 min 1-2 3-5 after meals
c) Intermediate-acting, NPH
- Insulatard®* 1.5 Hr 4-12 18-23 Pre-breakfast /
Pre-bed
- Humulin N®* 1 Hr 4-10 16-18
d) Long-acting analogue Same time

- Glargine®* 2-4 Hr peakless 20-24 everyday at
- Detemir®* 1 Hr peakless 17-23 anytime of the
day
e) Premixed human (30%

regular insulin+ 70% NPH) 30-60 mins
- Mixtard® 30* 30 min dual 18-23 before meals
- Humulin® 30/70* 30 min dual 16-18
f) Premixed analogue
- NovoMix® 30
(30% aspart + 70%
aspart protamine)* 10-20 min dual 18-23
- Humalog Mix® 25 5-15 mins
(25% lispro + 75% before meals
lispro protamine* 0-15 min dual 16-18
* Available at Ministry of Health, Malaysia.
N.B. The time course of action of any insulin may vary in different individuals, or at
different times, or at different injection locations in the same individual. Due to such
variations the time periods described above should be used as general guidelines only.
The short-acting and the intermediate-acting insulin can be self mixed as an alternative
to the human premixed insulin although this is not encouraged due to significant reduction
in the reproducibility of insulin action.
18
INSULIN TYPES AND REGIMENS
4.2 Comparison of Conventional Insulin and Insulin Analogues
Insulin analogue is derived from human insulin in which the amino acid sequence
is intentionally altered to produce an improved pharmacokinetic profile that
mimics physiological insulin secretion better.
• Prandial analogue mimics the first phase of insulin secretion in response to

a meal
• Basal analogue mimics the physiological basal insulin secretion in-between
meals and overnight
• Premixed analogue consists of both rapid-acting and intermediate-acting
insulin analogues and was developed to more closely mimic physiological
endogenous insulin secretion and meet the needs of patients who require
both basal and prandial insulin but wish to limit the number of daily injections
The differences between prandial, basal & premixed analogues compared to

human insulin are summarized in Table 4.2.
Individuals with the following situations should be considered for insulin analogue
therapy:
a) Rapid-acting analogue
- Delayed inter-meal hypoglycemia preventing achievement of postprandial
glycemic target on regular short-acting insulin
- Lifestyle restriction, the need to eat immediately after insulin injection due
to job schedule etc.
- Variable carbohydrate intake
b) Long-acting analogue
- Nocturnal hypoglycemia on intermediate-acting insulin (NPH) preventing
achievement of target fasting blood glucose
- Inadequate basal insulin coverage with once daily intermediate-acting insulin
(NPH) and not willing to go on NPH twice daily
19
Table 4.2 Comparison of conventional and analogue insulin2,3,4
Characteristics Conventional Analogue

PRANDIAL INSULIN
Onset Delayed Immediate

Administration 30 min before meals With meals
Postprandial glycemic control + ++
Inter-meal hypoglycemia ++ +
Inter-meal hyperglycemia + ++
Dosing flexibility + ++
Pharmacokinetics Less physiological More physiological
Cost Lower Higher
BASAL INSULIN
Duration < 24Hr ~24Hr

Peak Pronounced Absent / minimal
Nocturnal hypoglycemia ++ +
Absorption Variable Reproducible
Weight gain ++ +/- (detemir)
Cost Lower Higher
PREMIXED INSULIN
Administration 30min before meals With meals
Postprandial glycemic control + ++
Inter-meal hypoglycemia ++ +
Dosing flexibility + ++
Dosing interval Once to twice daily Once to thrice daily
Cost Lower Higher
20
4.3 Insulin Regimen
4.4 An ideal insulin regimen should mimic the physiological insulin response to
meals and endogenous hepatic glucose production. The various types of insulin
regimen can be classified as below (Table 4.3).
The choice of insulin regimen should be individualised, based on the patient’s

glycemic profile, dietary pattern, personal lifestyle as well as desired flexibility.
Table 4.3 Insulin regimens and frequency of injections per day
No. of
injections Insulin regimen Type of insulin and timing
per day
BASAL Intermediate acting (NPH) insulin pre-bed

1 BASAL Long-acting analogue once daily
PREMIXED OD Premixed/ premixed analogue pre-dinner
BASAL Intermediate acting (NPH) pre-breakfast and pre-dinner

2 PREMIXED BD Premixed insulin pre-breakfast and pre-dinner
BASAL-PLUS (1) Basal insulin once daily + 1 prandial insulin
BASAL-PLUS (2) Basal insulin once daily + 2 prandial insulin

PRANDIAL Prandial insulin pre-breakfast, pre-lunch and pre-dinner
Premixed analogue pre-breakfast, pre-lunch and
PREMIXED TDS pre-dinner
3
PREMIXED-PLUS Premixed insulin pre-breakfast, pre-dinner +
1 prandial insulin pre-lunch
PREMIXED-PLUS Prandial insulin pre-breakfast and pre-lunch +

premixed insulin pre-dinner
BASAL-BOLUS Basal insulin once daily + prandial insulin

4
pre-breakfast, pre-lunch and pre-dinner
Intermediate acting (NPH) insulin pre-breakfast
5 BASAL-BOLUS and pre-dinner + prandial insulin pre-breakfast,
pre-lunch and pre-dinner
Apart from insulin pump therapy, basal bolus therapy using the combination of
long-acting basal and rapid-acting analogue offers the regimen that most closely
mimics the endogenous insulin action at the expense of increased number of
injections.
21
REFERENCES
1. DeWitt DE et al. Outpatient insulin therapy in type 1 and type 2 diabetes

mellitus: Scientific review. J Am Med Assoc. 2003; 289:2254-64.
2. Raskin P et al. Use of insulin aspart, a short-acting insulin analogue as the

meal time insulin in the management of patients with type 1 diabetes.
Diabetes Care. 2000; 23:583
3. Manucci E et al. Short-acting insulin analgues versus regular human insulin

in type 2 diabetes: a meta-analysis. Diabetes, Obes & Metab. 2009; 11:53-59.
4. Qayyum R et al. Systematic review: Comparative effectiveness and safety of

premixed insulin analogues in type 2 diabetes. Ann Intern Med. 2008; 149:
549-59.
Section
5
INSULIN INITIATION
AND OPTIMISATION
Practical Guide to
Insulin Therapy in
23
INSULIN INITIATION AND OPTIMISATION
Implementing successful insulin therapy requires a 3 stage process;

1. Initiation – Starting insulin. Requires selection of appropriate insulin regimen,
insulin type and starting dose to address the individual’s main glycemic
abnormality.
2. Optimisation1 – Dose titration / adjustment. Requires gradual, safe and

prompt titration of insulin dose according to self blood glucose monitoring
(SMBG), towards an optimal dose to ensure maximum benefit from prescribed
treatment. The insulin dose should be adjusted at least weekly to get the
monitored readings to target. Optimisation of the insulin dose should be an
interactive process between the healthcare provider and the patient. This can
be done at the diabetic resource centre or via telephone calls. It should be
done within the first few months of starting insulin.
3. Intensification – Modification of an insulin regimen to achieve better glycemic

control requires switching to more intensive insulin regimens for better
glycemic control.
There are a few choices when starting insulin (Table 4.1a). The insulin regimen
and insulin doses initiated are individualized, based on blood glucose profile,
patient’s lifestyle and preferences (Table 5.1).
Table 5.1 Selecting initial insulin regimen based on blood sugar profile:
Blood Glucose Profile
Preferred insulin regimen
Pre-Breakfast Daytime
High Normal Pre-bed intermediate / long acting insulin (BASAL)
Pre-bed intermediate / long-acting insulin and later

add on prandial short / rapid acting insulin
High High (BASAL → BASAL PLUS / BASAL BOLUS) or
(PRE-BREAKFAST AND PRE-DINNER
PREMIXED INSULIN)
Prandial short / rapid acting insulin and later add
Normal High on basal insulin
(PRANDIAL → BASAL PLUS / BASAL BOLUS)
Starting T2DM patients on basal insulin is a well established treatment option for
improving glycemic control when OADs fail2. Supplementation with basal insulin
allows the reduction of HbA1c, primarily by targeting fasting plasma glucose
(FPG) – concept of 3Fs – “Fixing the Fasting First”.
For those patients who desire an easier insulin regimen but can cope with rigidity
of lifestyle, a premixed insulin regimen can be initiated2.
24
5.1 Initiating and Optimising Pre-bed Intermediate / Basal insulin
We can simply start the pre-bed intermediate/basal insulin at 10 units per day,
or alternatively, start based on body weight at 0.2 units/kg3. (In those patients
who are elderly, leaner or have milder fasting hyperglycemia, an initial dose of
0.1units/kg may be reasonable to ensure lower risk of hypoglycemia)
Patients are advised to perform SMBG at pre-breakfast. There should be at least

3 consecutive values before adjusting insulin dose. Monitoring-based dose
adjustment should be done after 3 to 7 days of initiating the last dose. The target
blood glucose is at 4 – 6 mmol/L.
If more than 1 of 3 pre-breakfast blood glucose values are less than 4 mmol/L,
reduce intermediate/basal insulin by 2 units. If all 3 values are within the targets
of 4-6 mmol/L, maintain current intermediate/basal insulin dose. If more than 1
reading of blood glucose is more than 6 mmol/L without any hypoglycemia,
basal insulin dose may be increased by 2 units (Table 5.2). Subsequently insulin
doses are gradually increased until target blood glucose is achieved.
The optimal dose of bedtime intermediate/basal insulin is generally at:

• Lean patient : 0.2 – 0.3 units/kg
• Most patients : 0.4 – 0.5 units/kg
• Obese patient : up to 0.7 units/kg
Table 5.2 Initiating insulin with basal insulin3,4
Treatment Dose
Initiation 10 units or 0.2U/kg at bedtime
(0.1 units / kg if higher risk for hypos)
Monitoring Monitor pre-breakfast BG
and targets Target pre-breakfast BG is at 4 - 6 mmol/L
Optimisation Adjust insulin doses after 3 consecutive BG values obtained

(every 3 – 7 days)
- < 4 mmol/L ( > 1 value ) → reduce dose by 2 units
- 4-6 mmol/L ( all values ) → maintain current dose
- > 6 mmol/L ( >1 value, no hypos ) → increase by 2 units
Optimal dose 0.2 – 0.3 units/kg in lean patients

0.4 – 0.5 units/kg in most patients
Up to 0.7 units/kg in obese patients
Caution Watch for nocturnal hypoglycaemia. If hypoglycemia is the limiting

factor to achieve optimum dose, conventional intermediate-acting
insulin may be switched to basal insulin analogue.
25
5.2 Initiating and Optimising Premixed Insulins3,4
Premixed insulin may be initiated once daily, usually at pre-dinner or twice daily
at pre-dinner and pre-breakfast (Table 5.3).
5.2.1 Premixed insulin once daily

The initial dose for once daily premixed insulin is usually 10 units or 0.2 units/kg
administered usually pre-dinner.
Patients are advised to perform SMBG at pre-breakfast. Titration is based on

3 consecutive readings of blood glucose (similar as for titrating intermediate/
basal insulin). The insulin dose should be adjusted weekly to get the monitored
readings to target.
During optimisation of pre-dinner premixed insulin:
• If more than 1 of 3 pre-breakfast BG is less than 4 mmol/L, reduce

pre-dinner premixed insulin by 2 units.
• If all 3 pre-breakfast BG are within the targets of 4-6 mmol/L, maintain
current pre-dinner premixed insulin dose.
• If more than 1 pre-breakfast BG is more than 6 mmol/L without any
hypoglycemia, may increase pre-dinner premixed insulin dose by 2 units.
5.2.2 Premixed insulin twice daily

The initial dose for twice daily premixed insulin is usually 10 units or 0.2 units/kg
twice daily administered at pre-breakfast and pre-dinner.
Patients are advised to perform SMBG at pre-breakfast and pre-dinner. Titration

is based on 3 consecutive readings of blood glucose (similar as for titrating
intermediate/basal insulin). The insulin dose should be adjusted weekly to get the
monitored readings to target.
During optimisation of pre-breakfast premixed insulin:
• If more than 1 of 3 pre-dinner BG is less than 4 mmol/L, reduce pre-breakfast

premixed insulin by 2 units
• If all 3 pre-dinner BG are within the targets of 4 - 6 mmol/L, maintain current
pre-breakfast premixed insulin dose
• If more than 1 pre-dinner BG is more than 6mmol/L without any
hypoglycemia, may increase pre-breakfast premixed insulin dose by 2 units
Titration for pre-dinner premixed insulin dose is similar as above.

26
Table 5.3 Initiating insulin with premixed insulin3

Treatment Dose
Initiation Once daily : 10 units or 0.2U/kg at pre-dinner
Twice daily : 10 units or 0.2U/kg at pre-breakfast and
pre-dinner
(0.1units/kg if higher risk for hypos)
Monitoring Once daily : Monitor pre-breakfast BG

and targets Twice daily : Monitor pre-breakfast and pre-dinner BG
Target pre-meal BG is at 4-6mmol/L
Optimisation Adjust insulin doses after 3 consecutive BG values obtained

Pre-breakfast BG determine pre-dinner premixed dose adjustment
Pre-dinner BG determine pre-breakfast premixed dose adjustment
Optimal dose Total daily dose of 0.5 – 1.0 units/kg in most patients
(Maybe more than 1.0 units/kg/day in obese, insulin
resistant patients)
Caution Watch for in between meal hypoglycaemia. If hypoglycemia is the

limiting factor to achieve optimum dose, conventional premixed
insulin may be switched to premixed analogue.
5.3 Initiating and Optimising Prandial Insulin
Prandial insulin therapy can be initiated at a dose of 6 units per meal, or altern-
tively, started based on body weight at 0.1units/kg per meal administered 30
minutes prior (short-acting insulin) or just before (rapid-acting analogue) the meal
(Table 5.4). Optimisation of prandial insulin doses are dependent on:
• Meal types and amount

• Pre-meal blood glucose levels on SMBG
27
If conventional short-acting insulin is used, SMBG should be performed pre-meals

at pre-lunch, pre-dinner and pre-bed. But, if rapid-acting insulin analogue is
used, BG may be monitored 1.5 - 2 hours post-meals. Following 3 consecutive
readings, insulin dose adjustment should be done on a weekly basis until the
glycemic targets are met.
During optimisation of prandial insulin, insulin dose is titrated to next pre-meal

(& bedtime) target:
• If the pre-lunch BG levels are not to target, pre-breakfast insulin dose is

adjusted. (Post-breakfast BG level may be used for rapid-acting analogue)
• If the pre-dinner BG levels are not to target, pre-lunch insulin dose is adjusted.
(Post-lunch BG level may be used for rapid-acting analogue)
• If the pre-bed blood BG levels are not to target, pre-dinner dose is adjusted.
(Post-dinner BG level may be used for rapid-acting analogue)
Prandial insulin dose may be adjusted as the following4:
• If more than one BG level is less than 4 mmol/L, reduce the prior pre-meal
prandial insulin by 1- 2 units
• If more than one BG level is more than 6mmol/L without any hypoglycemia,
may increase prior pre-meal insulin dose by 2 units
• If all pre-meal BG on target, dose of prior pre-meal prandial insulin is
maintained
Patients on prandial insulin should ideally be instructed in the following skills:
• Carbohydrate counting by a certified dietician. Carbohydrate counting is a

recommended method of meal planning for patient who have diabetes.
Carbohydrate counting allows patients to adjust the amount of prandial insulin
administered based on how many grams of carbohydrate they eat at a meal
or snack
• Insulin to carbohydrate ratio (I:C ratio) specifies how many grams of
carbohydrate are “covered” by each unit of insulin. For example, a 1-unit-
per-10-grams-of-carb (1:10) ratio means that one unit of insulin covers 10
grams of carbohydrate
• Correctional dose adjustment for pre-meal hyperglycemia. This will allow
patients to adjust pre-meal prandial insulin dose in case BG levels are already
elevated or low prior to meals
28
Table 5.4 Initiating with prandial insulin

Treatment Dose
Initiation 6 units or 0.1units/kg for each meal with short-acting or

rapid-acting analogue.
Monitoring Pre-meals and pre-bed.

and targets (Postmeals 1.5 - 2 hours if using rapid-acting analogue)
Target pre-meal BG is at 4 – 6 mmol/L
Target post-meals and pre-bed 4 – 8 mmol/L
Optimisation Adjust insulin doses after 3 consecutive pre-meal BG values obtained

Adjust the dose of prandial insulin of the preceding meal
(eg: if pre lunch BG is high, adjust pre breakfast prandial insulin)
Optimal dose Prandial dose for each meal will vary according to carbohydrate
content and amount.
Dose should ideally not exceed 0.5U/kg/dose.
Caution Watch for in-between meal hypoglycaemia. If hypoglycemia is the

limiting factor to achieve optimum dose, conventional short-acting
insulin may be switched to rapid-acting analogue.
5.4 Initiating and Optimising Basal Bolus Regimen
We can simply start this regimen by initiating prandial insulin at 0.1 U/kg or 6
units before each meal and basal insulin at 0.2 unit/kg or 10 units at
bedtime (Table 5.5).
SMBG should be performed pre-meals at pre-breakfast, pre-lunch, pre-dinner

and at bedtime/pre-bed for 3 consecutive readings and insulin dose can then
be adjusted accordingly.
Insulin dose adjustment for prandial and basal insulin is similar as that mentioned
in the prior sections 5.1 and 5.3. Aim for normal pre-breakfast BG first by
adjusting the dose of bedtime basal insulin before adjusting the prandial
insulin dose. Repeat this monitoring on a weekly basis until glycemic targets are
met.
29
Table 5.5 Initiating with basal-bolus regimen3,4

Treatment Dose
Initiation Prandial Insulin : 6 units or 0.1U/kg before each meal
Basal insulin : 10 units or 0.2U/kg at bedtime
Monitoring Preferably 4 times per day upon initiation
and targets Pre-meals at pre-breakfast, pre-lunch and pre-dinner and at bedtime
Target pre-meals BG at 4 – 6 mmol/L
Target bedtime BG at 4 – 8 mmol/L
Optimisation i: Prandial insulin:
Adjust insulin doses after 3 consecutive pre prandial BG values
obtained
Adjust the dose of prandial insulin of the preceding meal
(eg: if pre-lunch BG is high, adjust pre-breakfast prandial insulin)
ii: Basal insulin :

Adjust insulin doses after 3 consecutive BG values obtained
- > 6 mmol/L ( >1 value, no hypos ) → increase by 2 unit
Aim for normal pre-breakfast BG first by adjusting the dose of bed-
time basal insulin before adjusting the prandial (bolus) insulin dose.
Optimal dose Generally basal insulin would contribute 50% of total daily insulin
dose and prandial insulin would contribute remaining 50%
(distributed over three main meals).
Prandial insulin:
Dose for each meal will vary according to meal carbohydrate
content.
Normal prandial dose should not exceed 0.5u/kg/dose.
Basal insulin:
0.4 - 0.5 units/kg in most patients
Lean patients : 0.2 – 0.3 units/kg
Obese patients : Up to 0.7 units/kg
There is no limitation for insulin dose5, however, requirement of high insulin dose (>1.5
unit / kg per day) should prompt a search for an underlying cause or secondary problems
such as: non-compliance, incorrect dosing and administration timing, hypertrophy of
injection area, inter–meal hypoglycemia with rebound hyperglycemia pre-meal, expired
insulin, inappropriate insulin or inaccurate BGM and occult infections.
30
REFERENCES
1. Arshag DM et al Narrative Review: A Rational Approach to Starting Insulin

Therapy. Ann Intern Med. 2006;145:125-134.
2. Holman R et al. Three Year Efficacy of Complex Insulin Regimens in Type 2

Diabetes. N Engl J Med 2009;361:1736-47.
3. Bu BY. Type 2 diabetes mellitus-Guidelines for initiating insulin therapy.

Australian Family Physician 2007; 36(7):549-553.
4. Swinnen SGHA et al. Contact frequency determines outcome of basal insulin

initiation trials in type 2 diabetes. Diabetologia 2009; 52(11):2324-2327.
5. Clinical Practice Guidelines (CPG) on Management of type 2 Diabetes Mellitus

(4th Edition) 2009.
Section
6
INSULIN
INTENSIFICATION
Practical Guide to
Insulin Therapy in
32
INSULIN INTENSIFICATION
T2DM is a progressive disease. With increasing duration of disease, there is

increasing fasting and postprandial hyperglycemia as a result of progressive
pancreatic beta-cell failure. Therefore insulin therapy needs to be a dynamic
process, to address progressive insulin deficiency.
The use of a single insulin regimen may often not ensure durable glycemic control
over time despite optimisation of insulin doses. Many patients are left on an
inadequate insulin regimen for too long resulting in sub-optimal glycemic control.
Intensification enables modification of an insulin regimen, either with additional
injections or switching to different insulin types, towards achieving better
glycemic control.
Key elements for successful insulin intensification
• Patient education
• Dedicated diabetes team - diabetes educator, pharmacist, dietician
• Self-blood glucose monitoring (SMBG)
• Frequent contact with health care team
• Support group
Insulin intensification can be done in many ways. The choice would depend
on the pre-existing insulin regimen, the abnormal glycemic pattern, patient
acceptance and lifestyle issues.
33
Basal insulin regimens can be intensified by any of the following ways

(Figure 6.1a)
• Switching to premixed regimen (usually twice daily)

• Addition of three pre-meal rapid / short-acting insulin – basal-bolus regimen
• Sequential addition of pre-meal rapid / short-acting insulin – basal-plus
regimen
Figure 6.1a
Insulin Intensification from basal regime
BASAL
BASAL PLUS
PREMIXED BD BASAL BOLUS
(1 PRANDIAL)
BASAL PLUS
(2 PRANDIAL)
BASAL BOLUS
(3 PRANDIAL)
Premixed insulin regimens can be intensified by any of the following ways

(Figure 6.1b)
• Additional injections of premixed insulin (twice and three times daily)

• Addition of pre-meal rapid / short-acting at lunch
Figure 6.1b
Insulin Intensification from premixed regime
PREMIXED OD
PREMIXED BD
PREMIXED TDS PREMIXED BD

(FOR ANALOGUES) PLUS
PRELUNCH / PRANDIAL
34
6.1 Switching from Basal to Basal plus regimen
For those patients on combination OADs and basal insulin not achieving HbA1c
targets despite optimal fasting BG, addition of prandial insulin to address
postprandial hyperglycemia will help improve overall glycemic control. This can
be initiated with addition of single prandial insulin prior to the largest meal of the
day or to address the highest postprandial BG of the day1,2.
With time, additional prandial insulin can be added prior to other meals to address
postprandial hyperglycemia. (Figure 6.2). Intensification of the Basal – Plus
regimen (sequential addition of prandial insulin) will ultimately lead to Basal –
Bolus regime.
Figure 6.2 Intensification from Basal to Basal – Plus regimen
• Fix Fasting Blood Glucose (FBG) first using basal insulin (dose optimisation)
• Goal FBG 4 – 6 mmol/L
• Consider adding bolus / meal insulin when:
Hb A1c > 7% and FBG at goal or basal insulin dose > 0.5U/kg
• Add prandial insulin 6 units or 0.1unit/ kg at largest meal

• Titrate to next pre-meal / bedtime BG target daily
• If subsequent premeals BG are
• Discontinue SU on addition of prandial insulin
• Continue metformin
• Patients may need to perform SMBG up to 4 times per day
If A1c > 6.5 - 7% after 3 months despite titrating doses, or

prandial dose > 30 U per meal, consider:
• Add second prandial insulin at 6 units or 0.1 unit/kg at 2nd largest meal and
titrate as before
• Repeat 3rd prandial insulin dose at final meal of the day
35
6.2 Switching from Basal to Basal bolus regimen
targets despite optimal fasting BG, with post-prandial hyperglycemia identified
following all main meals, addition of prandial insulin prior to each meal will help
improve overall glycemic control. (Figure 6.3). Sulphonylureas should be stopped
but Metformin should be continued.
Figure 6.3. Intensification from Basal to Basal – Bolus regimen
• Fix Fasting Blood Glucose (FBG) first using basal insulin

(dose optimisation)
• Goal FBG 4 – 6 mmol/L
• Consider adding bolus / meal insulin when:
Hb A1c > 7% and FBG at goal or basal insulin dose > 0.5U/kg
• Add bolus / prandial insulin 6 units or 0.1unit/kg at each meal

• Monitor BG up to 4 times per day
• Titrate to next pre-meal / bedtime BG target daily
• If subsequent pre-meals BG are
• Stop SU and continue metformin
If HbA1c > 6.5 - 7% after 3 months despite titrating prandial doses or prandial
doses > 30 units per meal, consider:
• Resume titration / optimisation of basal insulin up to 0.7 U/kg
• Perform 7- point BG profile
36
6.3 Switching from Basal to Premixed regimen
targets despite optimal fasting BG, with post-prandial hyperglycemia, another
option for intensification would be to switch to a premixed regimen.
This option is usually appropriate for patients who prefer a simpler regimen and
are unable to accept 3 – 4 injections per day. This regimen is more suitable for
those with a rigid lifestyle. Sulphonylureas should be stopped but Metformin
should be continued.
Dose for dose transfer can be used where the total daily dose of basal insulin is
used to determine premixed total daily dose. Premixed is then administered in
two divided doses, usually equal in amount ie: split dose 50: 50 at pre-breakfast
and pre-dinner (Figure 6.4).
Figure 6.4 Intensification from basal to premixed regimen
BASAL OD or BD
HbA1c 6.5 – 8% HbA1c > 6.5 – 7%

FPG > 6 mmol/L FPG 4-6 mmol/L
Titrate basal insulin to Switch to PREMIXED

achieve FPG < 6mmol/L TWICE DAILY
• Optimal dose 0.4 – 0.5 u / kg • Total dose transfer
• Continue OADs • Split dose 50:50
pre-breakfast : pre-dinner
• Titrate dose once / twice a
week to next preprandial goal
• Stop SU, continue metformin
• Consider premixed analogue
Premixed analogues may be considered in patients experiencing hypoglycaemia

with conventional premixed insulin and in those who desire greater flexibility as
administration of premixed analogue does not require specific timing prior to
meals and may be injected just prior to, during, or immediately after, a meal.
37
6.4 Switching from Premixed to Basal bolus regimen
For those patients on premixed regimen (twice or three times daily) and not
achieving HbA1c targets despite optimised dose, another option for intensification
would be to switch to basal-bolus regimen.
This option is appropriate for patients who require greater flexibility in dose
adjustment as it potentially allows pre-meal rapid / short-acting insulin to be
adjusted individually according to blood glucose level (correctional bolus) as well
as the carbohydrate meal content of the meal.
Figure 6.5 Intensification from premixed regimen to basal bolus regimen
PREMIXED INSULIN BD or TDS

(Insulin analogue)
FPG / premeals > 6 mmol/L

HbA1c > 6.5 – 7%
Switch to BASAL BOLUS REGIMEN

• Starting dose 0.5units/kg/day or total dose transfer
• Split dose 50:50 for basal and prandial insulin
• Divide prandial doses into 3 main meals
• Fix FPG < 6mmol/L using basal insulin
• Titrate bolus dose once / twice a week to achieve FP and preprandial
goal < 6mmol/L
• Stop SU, continue metformin
The initial total daily dose following the switch may be guided by using a simple
dose calculation of 0.5units/kg or by a total dose for dose transfer from the prior
total daily dose on the previous regimen. Following determination of total daily-
dose requirement, proportion of basal to prandial insulin requirement may be
estimated using a ratio of 50:50. A smaller proportion of basal insulin may also
be used such as between 25 – 40% of total daily dose in certain circumstances.
The basal dose is usually administered at bedtime (conventional insulin) and the
prandial portion is divided into three to cover the three main meals, administered
pre-meals. Estimation of the pre-meal dose should take into consideration the
size of the meal, in terms of the carbohydrate content. Subsequently the basal
and pre-meal insulin should be titrated or optimised accordingly towards attaining
glycemic targets (Figure 6.5).
38
6.5 Switching from single to multiple premixed regimen
For those patients already on a single premixed insulin regimen, usually in

combination with single or multiple OADs and not achieving blood glucose and
HbA1c targets despite optimising insulin and OAD doses, an option for
intensification would be to initiate additional pre-meal doses of premixed insulin.
For those on single dose conventional premixed insulin, usually prior to evening
meals, one additional dose may be initiated prior to the morning meal. In those
receiving premixed analogue insulin, additional doses may be initiated at both
morning and midday meals, either sequentially or simultaneously. It is not usual
to administer conventional premixed insulin more than twice daily in view of
concern for between-meal hypoglycaemia3,4,5,6.
Figure 6.6 Intensification of premixed regimen
PREMIXED OD (pre-dinner) or BD
FPG and / or pre-dinner

4-6 mmol/L FPG and / or pre-dinner > 6 mmol/L
Titrate Premix OD or BD to achieve

HbA1c > 6.5 – 8%
FPG and / or predinner < 6mmol/L
SWITCH TO PREMIXED BD OR TDS (analogues only)
DAILY (OD) → TWICE DAILY (BD) TWICE DAILY (BD) → THREE TIMES
• Starting dose 0.3units/kg/day DAILY (TDS)
or total dose transfer • Add 6 units or 10% total daily dose
• Split the dose 50:50 at lunch
pre-breakfast and pre-dinner • Titrate dose once or twice a week to
• Titrate insulin dose to achieve next pre prandial goal < 6mmol/L
FPG and pre-dinner<6mmol/L • Down titrate morning dose
( 2 – 4 units ) may be needed after
adding lunch dose
• Continue metformin
• Consider premixed analogues if hypos
39
6.6 Intensification of premixed regimen with addition of

pre-meal bolus
For those patients already on a premixed daily regimen usually in combination

with single or multiple OADs and not achieving blood glucose and HbA1c targets
despite optimising insulin and OAD doses, an option for intensification would be
to initiate additional injections of pre-meal rapid or short-acting insulin.
Whereas for those patients already on premixed twice daily regimen and not
achieving blood glucose and HbA1c targets despite optimising insulin doses,
an option for intensification would be to initiate pre-lunch rapid or short-acting
insulin.
Figure 6.7 Intensification of premixed regimen with addition of prandial insulin
PREMIXED OD (pre-dinner) or BD
PREMIXED ONCE DAILY PREMIXED TWICE DAILY

(pre-dinner) (pre-breakfast, pre-dinner)
Pre-dinner >6 mmol/L

FPG 4-6 mmol/L, pre-lunch
Add PRANDIAL INSULIN
and pre-dinner > 6mmol/L
(at midday meal)
Add PRANDIAL INSULIN
(at morning and midday meal)
• Add prandial insulin 6 units

or 0.1unit/kg at lunch
• Titrate to pre-dinner BG target daily
• If subsequent pre-meal BG is
- < 4 mmol/L ( > 1 value )
→ reduce dose by 2 units
- 4-6 mmol/L ( all values )
→ maintain current dose
- > 6 mmol/L ( >1 value, no
hypos ) → increase by 2 units
40
6.7 Intensification of prandial regimen with addition

of basal insulin
For those patients already on prandial only regimen usually with each meal
and not achieving HbA1c and blood glucose targets (particularly fasting BG
despite optimising doses of prandial insulin), an option for intensification would
be to initiate basal insulin, usually at bedtime. Basal insulin analogue may be
added in the daytime as an alternative to bedtime dosing. Therefore the prandial
regimen is intensified to a basal bolus regimen (Figure 6.8)7.
Figure 6.8 Intensification of prandial regimen with addition of basal insulin
PRANDIAL TDS
Optimised prandial doses
FPG > 6 mmol/L

HbA1c > 6.5 – 8%
Addition of BASAL INSULIN → BASAL BOLUS REGIMEN

• 10 units or 0.2U / kg at pre-dinner
• Monitor FPG , target 4-6 mmol/L
• Adjust basal insulin doses after 3 consecutive
BG values obtained (every 3 – 7 days)

41
REFERENCES
1. Insulin intensification strategies in type 2 diabetes: when one injection is no

longer sufficient A. J. Garber Diabetes, Obesity and Metabolism Special
Issue: Perspectives in Type 2 Diabetes: Incorporating the Latest Insulin
Analogue Strategies to Achieve Treatment Success Volume 11, Issue
Supplement s5, pages 14–18, November 2009.
2. Options for the intensification of insulin therapy when basal insulin is not
enough in type 2 diabetes mellitus D. Raccah Diabetes, Obesity and
Metabolism Special Issue: Insulin Glargine: Cornerstone Treatment for
Type 2 Diabetes Patients Volume 10, Issue Supplement s2, pages 76–82,
July 2008 (basalplus).
3. Garber AJ, Wahlen J, Wahl T et al. Attainment of glycemic goals in type 2

diabetes with once-, twice-, or thrice-daily dosing with biphasic insulin
aspart 70/30 (The 1-2-3 study). Diabetes Obes Metab 2006; 8: 58-66.
4. Bebakar WM, Chow CC, Kadir KA et al. Adding biphasic insulin aspart 30 once
or twice daily is more efficacious than optimizing oral antidiabetic treatment in
patients with type 2 diabetes. Diabetes Obes Metab 2007; 9: 724-32.
5. A. G. Unnikrishnan,1 J. Tibaldi,2 M. Hadley-Brown,3 A. J. Krentz,4 R.

Ligthelm,5 T. Damci,6 J. Gumprecht,7 L. Gerö,8 Y. Mu,9 I. Raz10 Practical
Guidance on Intensification of Insulin Therapy With BIAsp 30: A Consensus
StatementInt J Clin Pract. 2009;63(11):1571-1577.
6. Intensification lessons with modern premixes: From clinical trial to clinical

practice Serdar Gulera, Julius A. Vazb, Robert Ligthelmc Volume 81,
Supplement 1, Pages S23-S30 (1 September 2008).
7. Intensification with prandial insulin. Pfützner A, Forst T .Int J Clin Pract

Suppl. 2009 Oct;(164):11-4.
Section
7
TARGETS
AND MONITORING
Practical Guide to
Insulin Therapy in
43
TARGETS AND MONITORING
Achieving glycaemic targets is central to reducing diabetes-related complications.

In most patients insulin given in sufficient doses and carefully titrated will
achieve those targets, and often more readily than with oral agents.
As a general rule, therapy should be directed to achieve an HbA1c of below

6.5% as this has been shown to reduce both microvascular and macrovascular
complications. It is increasingly recognised however that glycaemic targets
should be individualised.
Long-term follow-up of UKPDS and DCCT cohorts suggests that patients with
little co-morbidity and a long life expectancy may benefit from stringent
glycaemic targets early in the disease1,2,3.
Other recent studies4,5 assessing macrovascular outcomes indicate that less

stringent targets may be appropriate in the following situations:
• A history of severe hypoglycaemia

• Patients with limited life expectancy
• Advanced microvascular or macrovascular complications
• Extensive co-morbidities
• Long-standing diabetics in whom glycaemic control remains difficult despite
optimising patient education, adherence and dosage6.
7.1 Glycaemic targets for diabetes mellitus7

Glycemic Measures Targets
Fasting Blood Glucose (FBG) 4.4-6.1 mmol/L
Non-fasting Blood Glucose 4.4-8.0 mmol/L
HbA1c < 6.5%
Malaysian Ministry of Health CPG, Management of T2DM 2009
Individualised targets for self-monitoring of blood glucose may be discussed and

agreed upon after taking patient factors and limitations into consideration.
44
7.2 Monitoring insulin therapy
Techniques of monitoring insulin therapy include:

• Fasting Plasma Glucose (FPG)
• Glycosylated haemoglobin (HbA1c)
• Self-monitoring of blood glucose (SMBG)
• Continuous glucose monitoring (CGM)
7.2.1 Fasting Plasma Glucose (FPG)
Measurement of FPG is an established component of glycemic monitoring in most

outpatient settings. It is inexpensive and widely available. However single-point
glucose measurements may not accurately depict overall glycaemic control. This
is important to bear in mind when making therapeutic decisions.
7.2.2 Glycosylated haemoglobin (HbA1c)
HbA1c levels reflect average glycaemic control over 2-3 months. This affords an
advantage over single-point glucose measurements, however it may not reflect
glucose variability.
HbA1c should be performed at least 6-monthly in patients who are on stable

treatment and are meeting glycaemic targets. In patients’ not meeting targets
or in whom there has been a change in therapy, HbA1c levels should be
performed 3-monthly. Special situations may require monitoring at closer
intervals e.g. in pregnant diabetics requiring intensive insulin therapy.
7.2.3 Self-Monitoring of Blood Glucose (SMBG)
SMBG allows patients to evaluate their individual response to lifestyle, meals and
therapy, and to assess whether glycaemic targets are being achieved. It is
particularly important in insulin self-titration and may help minimise hypoglycae-
mia. As self-monitoring is both instrument and user-dependent, involvement of
a diabetes educator is crucial.
SMBG should be carried out at least 3-4 times daily in patients on multiple insulin
injections or insulin pump therapy i.e. before each meal and before bed (10-
11pm). Once pre-prandial glucose targets are achieved, post-prandial BG testing
is recommended for fine-tuning of insulin therapy.
45
Recommended timing of SMBG in different insulin regimens
Please refer to tables 7.2.3a and 7.2.3b
Table 7.2.3a SMBG in Basal / Basal bolus Regimen

Breakfast Lunch Dinner Bedtime
Pre Post Pre Post Pre Post Pre
Basal only X
Basal bolus X X X X
(short-acting)
Basal bolus X X X X
(rapid-acting)
Note
• Pre-breakfast glucose readings reflect adequacy of pre-bed basal insulin
• Pre-lunch readings reflect adequacy of pre-breakfast short-acting insulin
• Pre-dinner readings reflect adequacy of pre-lunch short-acting insulin
• Pre-bed readings reflect adequacy of pre-dinner short-acting insulin
• Post-prandial glucose readings reflect the respective pre-meal rapid-acting insulin
(Aspart/Lispro/Glulisine) and can also be used to fine-tune short-acting insulin
Table 7.2.3b SMBG in Premixed Regimen

Breakfast Lunch Dinner Bedtime
Pre Post Pre Post Pre Post Pre

Pre-mixed X X X X
Human BD
Pre-mixed X X X X
Analogues BD
Pre-mixed X X X X X X
Analogues TDS
Note
SMBG in Premixed regimen
• Pre-breakfast glucose readings reflect pre-dinner premixed insulin
• Pre-lunch and pre-dinner readings reflect pre-breakfast premixed insulin
• Pre-bed readings reflect pre-dinner premixed insulin
• Post-prandial testing may be recommended for fine-tuning of pre-mixed insulin
46
SMBG pattern management
This is a systematic approach to identifying patterns within SMBG data and then
taking appropriate action based upon results. It consists of four basic steps:
Step 1 Identify glycemic abnormality:

• Priority 1 – Hypoglycaemia
• Priority 2 – Fasting hyperglycemia
• Priority 3 – Postprandial hyperglycemia
Step 2 Determine timing and frequency of occurrence

• Prior to meals, after meals, during night?
• Occurs frequently or intermittently?
Step 3 Investigate potential causes

• Insulin and OADs, food and/or physical activity
Step 4 Take action

• Insulin and OADs, food and/or physical activity
SMBG and insulin titration / adjustment
Table 7.2.3 c SMBG and Insulin Titration

TO CONTROL ADJUST
Pre Breakfast BG Pre-bed intermediate/long-acting insulin or pre-dinner

premixed
2-hours Post-breakfast BG Pre-breakfast rapid-acting or premixed insulin analogue.
Pre-lunch BG Pre-breakfast short-acting or premixed insulin.
2 hours Post-lunch BG Pre-lunch rapid-acting or pre-breakfast premixed insulin.
Pre-dinner BG Pre-lunch short-acting or pre-breakfast premixed insulin.
Post-dinner/Pre-bed BG Pre-dinner rapid-acting or pre-dinner premixed insulin.
7.2.4 Continuous Glucose Monitoring (CGM)
CGM is not widely available but is an evolving technology which may benefit
selected patients. It employs interstitial glucose measurement via sensors placed
subcutaneously in the abdomen. These readings are transmitted to a monitor
and generally correlate well with plasma glucose. However, SMBG is still
recommended to calibrate CGM and for making acute treatment decisions.
Studies using CGM suggest some benefit for patients with Type 1 diabetes.
47
REFERENCES
1. UKPDS Study Group. UKPDS 16. Overview of six years’ therapy of type
2 diabetes – a progressive disease. Diabetes 44, 1249–1258 (1995).
2. Diabetes Control and Complications Trial, NEJM 329(14), September 30,

1993.
3. The Epidemiology of Diabetes Interventions and Complications Trial, NEJM

353(25), December 22, 2005.
4. Effects of Intensive Glucose Lowering in Type 2 Diabetes, the ACCORD study

group, NEJM 2008.
5. Dluhy RG et al. Intensive Glycemic Control in the ACCORD and ADVANCE

Trials; NEJM 2008.
6. Standards of Medical Care in Diabetes 2010, American Diabetic Association.
7. Clinical Practice Guidelines (CPG) on Management of type 2 Diabetes Mellitus

(4th Edition) 2009.
Section
8
PROBLEMS WITH
INSULIN THERAPY
Practical Guide to
Insulin Therapy in
49
PROBLEMS WITH INSULIN THERAPY
8.1 Hypoglycaemia
Hypoglycaemia is less common in people with T2DM than in those with T1DM.
However, this problem has become progressively more frequent with advanced
duration of T2DM and the use of intensive insulin therapy1. In a recent T2DM
survey, 50% of insulin-treated patients with T2DM self-reported hypoglycaemic
events in the preceding month2. In the UKPDS, intensive SU and insulin therapy
in non-obese, newly-diagnosed patients with T2DM was associated with the
highest cumulative incidences of hypoglycaemia over a six-year period, occurring
in approximately three-quarter of patients receiving insulin therapy and almost
half of those receiving SU. The incidence of major hypoglycaemia was much
greater with insulin therapy (11.2%) compared to SU therapy (3.3%) 3.
Hypoglycaemia has a negative impact on physical and psychological well-being.

Hypoglycaemic episodes are associated with several serious consequences such
as cardiovascular death, MI, cardiac arrhythmias, cardiac ischaemia, progressive
neuroglycopenia and autonomous nervous system abnormalities4. Hypoglycaemia
and fear of hypoglycaemia are important limiting factors in glycemic management
and may become significant barriers to treatment adherence. For instance,
patients may stop taking their anti-diabetic medication resulting in poor glycemic
control. In the Diabcare-Asia 2003 survey involving 15,549 patients with diabetes
(96% had T2DM), 54% of patients were anxious about the risk of hypoglycaemia
most of the time5.
There is no current consensus on a definition for hypoglycaemia. Recent

definitions by the American Diabetes Association (ADA), Canadian Diabetes
Association (CDA) and the European Medicines Agency (EMEA) have assigned
a threshold for the diagnosis of hypoglycaemia as a blood glucose level less than
3.9 mmol/L6.
Hypoglycaemia manifests as neuroglycopenic or neurogenic symptoms or both.4,7

(Table8.1a)
Table 8.1a Clinical manifestations of hypoglycaemia

Neurogenic / Autonomic Neuroglycopenic
Adrenergic
Palpitations Cognitive dysfunction
Tremor Behavioral changes
Anxiety/arousal Psychomotor abnormalities
Seizure
Cholinergic Coma
Sweating Brain damage
Hunger Death
Paresthesia
50
The severity of hypoglycaemia can be defined by its clinical manifestations.

• Mild - Autonomic symptoms present and the individual is able to self-treat
• Moderate - Autonomic and neuroglycopenic symptoms present and the
individual is able to self-treat
• Severe - Unconsciousness may occur. Plasma glucose is typically
< 2.8 mmol/L and the individual requires the assistance of another person
Severe hypoglycaemia requiring hospitalisation is more common in elderly

patients with T2DM. These events can have serious, sometime life-threatening,
cardiovascular and neurological consequences resulting in increased healthcare
costs. Elderly patients have a higher risk of complications such as falls and injury,
cognitive decline, depression and deteriorating quality-of-life.
Asymptomatic hypoglycaemia is the presence of biochemically low blood glucose

level without any symptoms. This can be seen in some insulin-treated patients
with advanced duration of diabetes or some patients who suffer from autonomic
dysfunction and frequent exposure to hypoglycaemia episodes. Symptoms of
hypoglycaemia may be absent despite significantly low blood glucose levels.
This phenomenon is described as hypoglycaemic unawareness. Hypoglycaemic
unawareness predisposes the patients to have recurrent hypoglycaemia events
which can be life threatening7.
Risk factors for hypoglycaemia in people with T2DM are

• Concomitant use of insulin secretagogues and insulin therapy
• Missed or irregular meals
• Alcohol consumption (in the absence of sufficient carbohydrate intake)
• Excessive physical activity
• Advanced age
• Longer duration of diabetes
• Impaired renal or liver function
• Impaired awareness of hypoglycaemia
• Lack of patient and care-giver education on hypoglycaemia
51
Prevention of hypoglycaemia requires risk factor reduction and individualised

treatment regimens. This will include therapy adjustment, flexibility in treatment
or a change in regimen adapting to each person’s needs and lifestyle. It is very
important to educate patients with diabetes to recognize the signs and symptoms
of hypoglycaemia and how to treat hypoglycaemia (Table 8.1b). Improved education
and recognition could prevent and reduce frequency of hypoglycaemic events.
Table 8.1b Treatment of hypoglycaemia
1. Assess the cause and severity of hypoglycaemia

2. Treat hypoglycaemia according to BG level
Mild ( BG 3.3 – 3.9 mmol/L ): Give 15g carbohydrate

4 ounces (120mls) orange juice or other fruit juices OR
Hard candy OR
3 glucose tablets
Moderate ( BG 2.5 – 3.2mmol/L ): Give 20g carbohydrate

6 ounces (180mls) orange juice or other fruit juices OR
4 glucose tablets OR
Dextrose 50% 25 ml iv
Severe ( BG < 2.5 mmol/L ): Give 30g carbohydrate

8 ounces (240ml) orange juice or other fruit juices OR
6 glucose tablets OR
Dextrose 50% 25 ml iv
Unconscious with severe hypoglycaemia ( BG< 2.5 mmol/L )

Dextrose 50% 25 ml IV OR
Glucagon 1 mg subcutaneous or intramuscular (0.5 mg for child)
- Vomiting and aspiration risk
- Roll patient onto their side when used
3. Monitor BG level every 15 minutes until > 5.6 mmol/L

4. Redose glucose replacement as above every 15 minutes as necessary (PRN)
52
8.2 Weight gain
Most patients with T2DM are overweight or obese. Many anti-diabetic

medications contribute to weight gain over time. In the UKPDS study (UKPDS
34)9: regardless of treatment, patients gained weight. Patients who were treated
with insulin showed the largest weight increase, with an average gain of 4 kg
more than conventional therapy at 10 years (UKPDS 33)10.
In other studies involving basal insulin use, weight gain of 2 to 3 kg has been
observed. Weight gain with insulin therapy is dose related. Use of more intensive
insulin regimens with increased total daily insulin requirement generally
contributes to greater magnitude of weight gain. The combination of insulin with
oral anti-diabetic agents such as TZDs and SUs result in greater weight gain
whereas combined use of insulin with metformin may help minimize weight gain.
Weight gain in insulin-treated patients may be a consequence of several factors:
• Improving metabolic control reduces glycosuria, thus fewer calories are lost
in this manner
• Fear of hypoglycaemia may lead to increased snacking between meals, thus
increasing calorie intake
• Use of insulin can increase lean body mass through its anabolic nature.
• Insulin use can also cause salt and water retention
It is important to provide patient education on measures to counter weight gain

while on insulin therapy. Important steps would be as follows
• Restrict calories and portion control, particularly carbohydrate and fats

• Appropriate advice from dietician
• Keep physically active and practise regular exercise
• Avoid high doses of insulin. Reducing carbohydrate intake and being
physically active reduces insulin requirement
• Prevent hypoglycaemia which leads to defensive eating / snacking
53
8.3 Injection site problems
Skin irregularities can sometimes occur at injection sites due to changes in the
subcutaneous fat, of which there are three types.
Fat hypertrophy (“lipohypertrophy”) appears as soft lumps at the injection sites.

This unusual condition may be caused by the natural effects of insulin (one of
which is to cause fat to grow) or by reuse of needles. To prevent further
development of hypertrophy, rotate injection sites and avoid reuse of needles.
Fat atrophy (“lipoatrophy”) is a loss of fat under the skin’s surface. This rare
condition appears as a dip in the skin and has a firm texture. It occurs much
more commonly with impure insulins.
Scarring of the fat (also known as “lipodystrophy”) is caused when you inject
too many times into the same site or when you reuse a needle.
8.4 Insulin allergy and hypersensitivity
In the past, when unpurified insulins were used, allergic reactions were reported
in 10% to 56% of patients. Since human insulin and analogues have been
introduced, insulin allergies are rare and currently reported in only 0.1% to 2%
of all patients treated with insulin. In most cases, allergic reactions are restricted
to the skin and are either of a local immediate or delayed reaction type. These
skin reactions are often self-limited with continuation of therapy. However,
systemic reactions such as urticaria or anaphylaxis have also been reported.
Both types of hypersensitivity may result from the insulin molecule itself, and
also from protamine, which is used in many preparations to delay insulin
absorption. In patients with diabetes mellitus, subcutaneous administration of
protamine-containing insulin preparations can provoke delayed, T-cell mediated
skin reactions or granulomatous hypersensitivity. In addition to protamine, cresol
and phenol, both preservatives in pharmaceutical products, may provoke allergic
reactions. Successful treatment of insulin allergies have been reported when
patients were using a continuous subcutaneous pump infusion of insulin and
switching from human insulin to insulin analogues such as aspart or lispro.
54
REFERENCES
1. UK Hypoglycemia Study Group. Risk of hypoglycaemia in types 1 and 2

diabetes: effects of treatment modalities and their duration. Diabetologia.
2007;50(6):1140–1147.
2. Lundkvist J et al. The economic and quality of life impact of hypoglycemia.

Eur J Health Econom. 2005;6(3):197–202.
3. UKPDS Research Group: Overview of 6 years of therapy of type II diabetes: a

progressive disease. Diabetes 44:1249–1258, 1995
4. Cryer PE. Hypoglycemia, functional brain failure, and brain death. J Clin Invest.
2007;117(4):868–870.
5. Mohamed M. An audit on diabetes management in Asian patients treated by

specialists: the Diabcare-Asia 1998 and 2003 studies Curr Med Res Opin
2008; Vol 24 No 2: 507–514.
6. Workgroup on Hypoglycemia, American Diabetes Association: Defining and

reporting hypoglycemia in diabetes: a report from the American Diabetes
Association Workgroup on Hypoglycemia. Diabetes Care 28:1245–1249, 2005.
7. Cryer PE et al. Hypoglycemia in diabetes. Diabetes Care 26:1902–1912, 2003.
8. Amiel SA et al. Hypoglycaemia in Type 2 diabetes . Diabet Med.

2008;25(3):245–254.
9. UK Prospective Diabetes Study (UKPDS) Group. Effect of intensive blood-

glucose control with metformin on complications in overweight patients with
type 2 diabetes (UKPDS 34). Lancet 1998 Sep 12 352 854-865.
10. 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 Sep 12;352(9131):837–53.
Section
9
SPECIAL
SITUATIONS
Practical Guide to
Insulin Therapy in
56
SPECIAL SITUATIONS
9.1 Sick Days

There may be times when the patient cannot eat solid food or follow their regular
meal plan because of concurrent illness, dental or outpatient surgery. Maintaining
glycemic control during periods of short-term illness is important to prevent
complications.
Potential problems during sick days are the following:

• dehydration
• ketoacidosis
• hyperglycemia
• hypoglycaemia
9.1.1 Hyperglycaemia
These are more common during illness particularly in viral illnesses with fever
(such as influenza or upper respiratory tract infection) or in bacterial illnesses
(such as tonsillitis or otitis media). BG levels will often still be high even if the
patient’s appetite is poor because of continuing release of glucose from the liver
and insulin resistance secondary to infection.
9.1.2 Hypoglycaemia
Gastroenteritis (vomiting and diarrhoea) often cause low BG levels even without
fever. The BG levels are low because the patient’s appetite is often decreased and
the food and drink that is taken is not being well absorbed.
During acute inter-current illness, insulin-treated patients will need to pay special
attention to monitoring and self-care practices. The following table indicates
principles in managing insulin-treated patients with acute intercurrent illness
(Table 9.1)
Table 9.1
“Sick Days” Rules. Patients are instructed on the following self-care.
• Treat underlying illness

• Symptomatic treatment eg: paracetamol for headache
• More frequent SMBG
• Maintain positive fluid balance: plenty of fluids, especially those with high
temperatures and high glucose
• Maintain adequate nutrition
• Insulin treatment may need adjustment
- Start out with usual insulin dose (except if AGE)
- Monitor BG pre-meals and between meals when needed
- Adjust insulin doses according to SMBG
- Additional rapid-acting insulin if blood glucose more than 15-16 mmol/L
57
9.1.3 Indications for hospital referral / admission

The following circumstances may indicate the need for hospital referral and
admission in insulin-treated patients with acute inter-current illness
• Voluminous or repeated vomiting

• Increasing levels of ketones in the blood or urine or labored breathing
• Blood glucose remains high despite extra insulin
• Absence of obvious precipitating factors
• Severe or unusual abdominal pain
• Confusion or deterioration in well being
• Presence of concurrent illnesses besides diabetes
• Exhaustion on the part of other person or their carer, eg: repeated night
waking
9.2 Travel1
During long distance travel, patients requiring insulin therapy will need to plan
travel and holidays in advance and seek advice wherever necessary. Ideally
glycaemia, blood pressure and lipids should be under control. It is important to
find out the types, formulations and strengths of insulin which are available in the
area of destination. The following table indicates the appropriate advice and
instructions to be given to insulin-treated patients who are intending to travel
long distance. (Table 9.2)
Table 9.2
Preparations for long distance travel for insulin users
• Take twice as much insulin, syringes or pens, needles or tablets as will

be needed
• If travelling with others, split the amount between each passenger’s hand
luggage just in case one of the bags is lost
• Bring a cool bag for storing insulin
• Bring adequate BG monitoring equipment (with strips, lancets, spare
battery)
• High altitude, heat and humidity can sometimes affect meters and test
strips. Be aware of possible false readings
• Bring carbohydrate (glucose tablets, sweets, snacks and juices) in the
hand luggage to cover any travelling delays in case of hypoglycaemia
• A diabetes identity card or medic alert bracelet.
58
SPECIAL SITUATIONS
Adjustment of insulin doses during long distance air travel
With long haul flights and crossing of time zones, there may need to adjust insulin
doses due to changes in mealtimes and activity during the flight. Travelling North
or South does not require any changes in 24 hour schedule.
Travelling East will shorten the day and therefore the need for less insulin,
meanwhile travelling West will lengthen the day and the need for more insulin.
During travelling, the insulin-treated patient is advised the following:
• Frequent blood glucose monitoring

• Planning of activities to match the insulin and meals
• Careful observation and selection of food and drinks to avoid food-borne
infection
• Advice on appropriate footwear and foot care
9.3 Exercise2
Physical activity / exercise is an integral part of the overall management of

insulin-treated patients. The following table states the benefits of exercise in
insulin-treated patients (Table 9.3a).
Table 9.3a
Benefits of exercise in insulin-treated patients
• Increases calorie expenditure with weight loss and maintenance of

healthy weight
• Increases insulin sensitivity and reduces insulin resistance, improves
glycemic control
• Reduces insulin requirement
• Improves lipid profile, reduces LDL-cholesterol and increases HDL-
cholesterol
• Lowers BP and reduces risks of CV disease and CV mortality
• Increases endorphin release, thereby reduces stress and improves mood
• Improves muscle strength
• Increases bone density and strength
Prior to exercise, insulin-treated patients should undergo the following evaluation:
• Complete Physical Exam, including foot, respiratory, cardiovascular

• Diabetic complication screening with assessment for proliferative retinopathy,
autonomic and peripheral neuropathy and nephropathy
59
Insulin-treated patients may experience unstable blood glucose levels in relation

to exercise with an increase risk of both hypoglycaemia and hyperglycaemia.
Risk of hypoglycaemia is due to reduced insulin resistance and reduced insulin
requirement while risk of hyperglycemia is a result of stress hormone release.
Advice is given to patients with regards to monitoring, lifestyle and insulin dose
adjustment prior to, during and after exercise as stated in Table 9.3b.
Table 9.3b
Recommendations on self-care and lifestyle adjustment with exercise
for insulin users
• Optimal time for exercise would preferably be 1-3 hours following meal
• SMBG should be performed before, during and after exercise
BG target at the start - between 5.5mmol/L to 11.1 mmol/L
If BG is < 4.4 mmol/L – advise to consume 15-20 grams carbohydrate
• 15-20 grams carbohydrate for prevention of hypoglycaemia, may need
additional consumption every 30-60 minutes. Carry sweet or snacks in
case of hypoglycaemia.
• Consider need for insulin dose reduction, vary between 25-75% reduction
• Watch for post-exercise hypoglycaemia
• If heavy exercise is planned, such as aerobics, running or handball,
extra calories should be consumed.
• Exercise should be avoided in the following circumstances;
Elevated BG > 16mmol/L
Acute inter-current illness
Positive ketonuria
Dyspnoea.
Symptomatic peripheral neuropathy - tingling, pain or numbness in
the legs
60
SPECIAL SITUATIONS
9.4 Fasting and Ramadan3
Insulin-treated patients who perform fasting are at risk of hypoglycaemia,

hyperglycaemia, diabetic ketoacidosis, dehydration and thrombosis. The severity
of risk for developing these complications differ according to several patient
factors as mentioned in Table 9.4a.
Table 9.4a
Severity of risk for complications during fasting for patients with
diabetes3
Very high risk group

• Type 1 diabetes
• Severe hypoglycaemia within the last 3 months prior to Ramadan
• Patient with a history of recurrent hypoglycaemia or hypoglycaemia
unawareness
• Ketoacidosis or Hyperosmolar hyperglycaemia within the last 3 months
prior to Ramadan
• Patients with sustained poor glycaemic control
• Patients with renal insufficiency, advanced macrovascular complications or
co-morbid conditions that present additional risk factors
• Acute concurrent or recent illness such as infection
• Poor compliance to anti-diabetic medications
• Pregnancy
Moderate risk
• Patients with moderate hyperglycaemia
• People living alone that are treated with insulin
• Patients living alone with ill health
• Old age with ill health
• Drugs that may affect mentation
• Patients who perform intense physical work
Low risk
• Well controlled patients treated with diet alone, metformin, or a
thiazolidinedione, who are otherwise healthy
• Well-controlled patients treated with prandial glucose regulators such as
repaglinide or nateglinide
61
Those patients at very high risk of complications are strongly advised to avoid
fasting whilst those insulin-users with satisfactory glycemic control and low risk
of severe hypoglycaemia may be allowed to perform fasting with strong
recommendations for more frequent blood glucose monitoring and appropriate
insulin dose adjustments. Use of insulin analogues (basal, short acting or premix
analogues) during fasting has been associated with less hypoglycaemia and
more effective postprandial BG control.
SMBG is advised for the following times

• Pre Sahur (pre-dawn meal) and 2 hours post Sahur
• Pre Iftar (Sunset) and 2 hours post Iftar
Insulin dose adjustments during fasting are as recommended in Table 9.4b4.
Table 9.4b
Dose adjustments for insulin regimens during fasting
Insulin Regimen Insulin Dose Adjustment
Bedtime basal insulin • Reduce basal insulin dose by 20%
with OADs • Insulin administered at Iftar time (sunset)
• Reverse OAD dose - morning to evening
dose and vice versa
Premixed insulin • Reverse doses – morning dose given at Iftar

twice daily (sunset) and evening dose at sahur
• Insulin dose at sahur reduced by 20-50% to
prevent daytime hypoglycaemia
Basal bolus • Basal dose given at Iftar, dose reduced by

20%
• Sahur/ morning dose of prandial insulin
reduced by 25%
• Mid-day/ lunch prandial insulin omitted
• Iftar prandial dose maintained, may be
adjusted according to carbohydrate content
in meals
All patients must always and immediately end their fast if:
• Hypoglycaemia (BG <3.5 mmol/l)

• BG reaches < 3.9 mmol/l in the first few hours after the start of the fast,
especially if insulin, has been taken at pre-dawn
• Blood glucose exceeds 16 mmol/l as higher risk for acute hyperglycaemic
complications and dehydration
62
SPECIAL SITUATIONS
9.5 Pregnancy
Diabetes during pregnancy presents major risks for poor fetal, neonatal, and
maternal outcomes. However, the risk can be greatly reduced by early institution
of medical nutritional therapy and insulin treatment. In a T2DM patient planning
to get pregnant, preconception counselling with optimisation of glycaemic control
prior to conception is of utmost importance. There is a need to consider initiating
insulin prior to conception and work towards achieving and maintaining target
HbA1c < 6.5%. Maintaining maternal glycaemia as near to normal as possible
reduces the risk of congenital anomalies, macrosomia, neonatal hypoglycaemia,
and large-for-gestational-age infants.
Insulin is considered the “gold standard” treatment in managing gestational

diabetes mellitus (GDM) and T2DM during pregnancy. In pregnancy, the common
insulin regime is basal bolus regime which enables easier insulin dose
adjustment and potentially better glycaemic control. The prandial insulins that can
be used are short-acting regular human insulin and the rapid-acting insulin
analogues. The basal insulin used in pregnancy is usually NPH as the evidence
for the use of long- acting insulin analogues in pregnancy is not as extensive5.
When estimating the starting insulin dose, the maternal weight and the pregnancy
gestation / trimester should be considered (Table 9.5). There is increased insulin
requirement as pregnancy progresses as a result of insulin resistance. In some
patients there may be a need for more than 1 unit / kg day total daily dose during
pregnancy, especially in obese women with T2DM and other features of metabolic
syndrome6.
Table 9.5a
Estimation
Pregnancy of total daily insulin requirement by gestation / trimester
gestation
Pregnancy gestation Total daily insulin requirement
1st trimester 0.7 units/kg/day
2nd trimester 0.8 units/kg/day
3rd trimester 0.9 units/kg/day
The insulin regimes used must be able to maintain good glycaemic control without
hypoglycaemia. SMBG is an important aspect in managing diabetes in pregnancy.
The targets of blood glucose during pregnancy are as outlined in CPG Management
of T2DM 2009 (Table 9.5b).
Table 9.5b Glycaemic Targets in Pregnancy
Timing Glucose Levels (mmol/L)
Pre-prandial 3.5-5.9
1 hour post-prandial <7.8
2 hours post-prandial 4.4-6.7
0200-0400H 3.9
(ADA recommends pre-prandial BG <5.3 mmol/L)
63
REFERENCES
1. National diabetes education program. Available from http://www.nedep.nih.

gov/media/diabetes_travel_article,pdf.
2. Diabetes and Exercise association. Available from http://www.diabetes-

exercise.org/presentaion/Horton_2009,pdf.
3. A population-based study of diabetes and its characteristics during the fasting

month of Ramadan in 13 countries: results of the epidemiology of diabetes
and Ramadan 1422/2001 (EPIDIAR) study. Diabetes Care. 2004
Oct;27(10):2306-11.
4. Recommendations for Management of Diabetes During Ramadan. Diabetes

Care,2010 Aug;33(8):1895-1902.
5. Angeline L et al .Insulin analogue and pregnancy .Diabetes Spectrum Vol 2,

2007.
6. Boyd et al.Summary and Recommendations of the 5th International Workshop

Conference on Gestational Diabetes Mellitus .Diabetes Care, Vol 30,
Supplement 2, July 2007.
Section
10
PRACTICAL
ISSUES
Practical Guide to
Insulin Therapy in
65
PRACTICAL ISSUES
10.1 Insulin handling and storage
Insulin comes from drug manufacturers in three basic packages; vials, pens and
cartridges/ penfills. Insulin vials, either open or unopened, generally last for one
month when stored at room temperature (15 – 30oC). All unopened vials should
be stored in the refrigerator (2 – 8oC) away from the freezer, and are good until
the expiration date printed on the label. A vial is considered open if its seal has
been punctured. Once opened and stored in a refrigerator the insulin should be
used within one month of being opened and discarded thereafter, regardless of
the expiration date, as there may be loss in potency. Vials that are currently in use
can be kept at room temperature as injecting cold insulin can be painful. Insulin
past the expiration date printed on the label should not be used. Patients are
advised to write the date the vial was opened on the label.
With insulin pens and their cartridges / penfills, storage life ranges from seven
days to one month1. There are different storage indications for every type of
insulin available, depending on the particular formulation of insulin, its method
of manufacture, its container and ambient storage conditions. In-use dating
recommendations for insulin in vials differ from cartridges or prefilled insulin
pens. Pens and cartridges have shorter in-use duration than those for vials,
reflecting the reduced volumes and the environment to which these products
might be exposed.2,3
66
PRACTICAL ISSUES
Maximum storage duration for insulin pens

Room
Refrigerated temperature
Opened /
Opened Unopened Unopened
Product name (Days)
Humulin® N Do not refrigerate Until Expiration Date Stamp 28

Humulin® 30/70 Do not refrigerate Until Expiration Date Stamp 28
Humalog® Do not refrigerate Until Expiration Date Stamp 28
Humalog® 25/75 Do not refrigerate Until Expiration Date Stamp 28
Actrapid® Do not refrigerate Until Expiration Date Stamp 42
Insulatard® Do not refrigerate Until Expiration Date Stamp 42
Mixtard® 30/70 Do not refrigerate Until Expiration Date Stamp 42
Novorapid® Do not refrigerate Until Expiration Date Stamp 28
Lantus® Do not refrigerate Until Expiration Date Stamp 30
Levemir® Do not refrigerate Until Expiration Date Stamp 42
The following tips are useful for insulin storage
• Protect insulin (vials, pens, and cartridges) from extremes of hot and cold
• Keep insulin out of direct sunlight
• Never store insulin in the freezer - once insulin is frozen, it loses its potency
• Don’t store insulin near radiators, heat-vents, ovens, air conditioners, etc.
• Don’t leave insulin in a closed car during very warm or cold weather
• If going outdoors for a while in hot or cold weather, store your insulin in an
insulated case
• Inspect insulin prior to each use. Observe for unusual appearance of insulin-
cloudy instead of clear, clumping, stringy or has changed in color. These
changes will probably lead to ineffective insulin and should be discarded
immediately and a new vial / cartridge / pen should be used
67
10.2 Insulin injection sites
The site of insulin injection greatly influences the absorption level and effective-
ness of the insulin. Insulin injection site rotation is as important as the amount
of insulin taken.
General tips with regards to injection sites.
1. Give injections in the abdomen, thighs and back of the upper arm
whenever possible.
Insulin is most rapidly absorbed when injected in the abdomen, followed by
the upper arm and thigh area. Injections in hip and buttock areas are more
slowly absorbed. Never inject within two inches of navel.
2. Choose a slightly new location for each injection.

This is called site rotation. For example, if all injections are given in the
abdomen, note of where the last injection was given and move the next one
about an inch to one side or the other. Continue to move the injection site
until all the available sites are covered before starting a new area.
3. Always inject insulin into fatty tissue instead of muscle.

That’s why the abdomen, upper back of the arms and outer thigh are
preferred. These areas are easy to reach and have ample amounts of
fatty tissue (called subcutaneous fat). These areas also reduce the risk of
injecting insulin too close to a large blood vessel or nerve.
4. Give your injections in the same general area at the same time each day.
For example, take the morning insulin in the abdomen and the afternoon or
evening insulin in the arm. This consistency helps the body better absorb
the insulin over random injections.
5. Keep accurate records of site rotation.

This will help avoid injecting the same area repeatedly. Doing so is likely to
result in the development of fat deposits that can make skin look lumpy and
delay the absorption of insulin.
68
PRACTICAL ISSUES
Front
Abdomen Abdomen
Front Front
and side and side
of thigh of thigh
Back
Upper Upper
and outer and outer
arm arm
Buttocks Buttocks
Side of Side of
thigh thigh
69
10.3 Insulin pen devices and needles
Insulin injections can be given using an insulin syringe and appropriate syringe
needles or with an insulin pen device and appropriate pen needles.
An insulin pen is a type of delivery system for administering insulin doses that
is used as an alternative to a syringe. Insulin pens use short and thin needles that
usually guard against any air flowing through. Insulin pens have made dispensing
insulin simple for patients at home or on the go, and can generally provide a
more accurate dosage than a syringe. There are a number of different brands
and models of insulin pens available. Most insulin pens fall into one of two
groups: reusable pens and disposable pens.
• A reusable insulin pen must be loaded with a cartridge / penfill of insulin

(available / sold in boxes of five cartridges). Cartridges / penfills hold 300 units
of insulin and may give enough insulin to last for several days. When the
cartridge is empty a new cartridge is loaded. With good care a reusable pen
can often be used for several years.
• Disposable insulin pens come pre-filled with insulin and are thrown away
when they are empty. Most disposable pens used hold 300 units of insulin
and are available / sold in boxes of five. Disposable pens are generally more
convenient because there is no need to load any cartridges, but usually cost
more to use than reusable pens and cartridges.
70
PRACTICAL ISSUES
Table 10.3 Insulin pens available in Malaysia1

Insulin Pen Pen Type Insulin Type
n® (Ergo)
HumaPen - Humulin R®
Reusable - Humulin N®
- Humulin® 30/70
- Humalog®
- Humalog® 25/75
Novopen® 3
- Actrapid®
Novopen® 4
- Insulatard®
Reusable
- Mixtard® 30/70
- Novorapid®
Novolet® - Actrapid®
Pre-filled /
- Insulatard®
disposable
- Mixtard® 30/70
Flexpen® Pre-filled / - Novorapid®

disposable - Novomix® 30
- Detemir®
SoloSTAR® Pre-filled / - Lantus®

disposable - Apidra®
71
10.4 Insulin Absorption
Variability of insulin absorption is perhaps the greatest barrier to replicating

physiologic insulin secretion4. The inter-individual and intra-individual insulin
absorption can pose a significant challenge to the health care provider during
insulin optimisation. Day-to-day intra-individual variation in insulin absorption
is approximately 25%, and the variation between individuals may be as high
as 50% 5. Factors that may affect insulin absorption include the following (Table
10.4):
Table 10.4 Factors influencing insulin absorption

Factors Comment
1. Site of injection Abdominal injection (particularly if above the
umbilicus) results in the quickest absorption; arm
injection results in quicker absorption than thigh
or hip injection
2. Injection volume Large volume injection is absorbed in a more

unpredictable manner compared to small volume
injection (i.e. < 10u)
3. Injection depth Patients should be advised to inject insulin at a

consistent depth to avoid unpredictable absorption
4. Needle length Absorption may be compromised if short needles
are used for a relatively thick subcutaneous tissue.
There are three needle sizes available in Malaysia,
i.e. 5mm, 6mm and 8mm
5. Insulin type Insulin analogue is generally absorbed in a more
predictable manner than conventional human insulin
6. Injection route Insulin is absorbed faster when administered

intravenously compared to intramuscular or
subcutaneously in a descending order
7. Exercise Exercising a muscle group before injecting insulin into

that area increases the rate of insulin absorption
8. Heat application Local application of heat or massage after an insulin

or Massage injection increases the rate of insulin absorption
72
PRACTICAL ISSUES
10.5 Insulin Injection problems
Beginning insulin therapy requires proper education regarding injection technique.

However, even with proper education by a certified diabetes educator problems
can still occur. Injection problems can occur with the use of a vial and syringe or
a pen device (Table 10.5)
Table 10.5 Common insulin injection problems

Problems Solutions
Painful injections • Review injection technique
• Try injecting at a 45° angle; to prevent hitting muscle
• Inject quickly
• Check that needle is not bent
• Inject insulin when it is at room temperature.
Cold insulin hurts
• Try injecting in different site
• Do not use needles more than once. Reusing needles can
bend and dull the tip and increase pain
• Keep the muscles at injection area relaxed
• Larger doses hurt more. May benefit from more frequent
injection with smaller amount
Bleeding at site • Do not rub the injection site

of injection • Apply light pressure with finger to prevent bruising
• If bruising, avoid that injection site again until the bruise
resolves
• Frequent bleeding may indicate poor technique or
another medical problem; inform healthcare provider
and/or diabetes educator
Insulin is • Wait at least 10 seconds after injecting before removing

dripping from the needle.
• Do not carry a pen with the needle attached.
the pen needle
This causes air to enter the cartridge, thus slowing the
after injection time it will take to get the insulin dose
Insulin leaking • Try using a longer needle (8mm).
from injection site • Try a different injection site
The injection • Small amounts of insulin may be caught in the needle

device is clogged from a previous use. Never re-use needles
• There may be a clump in the insulin: If using cloudy
insulin, be sure to properly mix insulin before drawing it up
• Cloudy insulin can dry inside the needle or syringe if
drawn up too far before the time of injection. Fill syringe
closer to the time of injection
Pen needles should be removed after each use to prevent air from entering the
cartridge and to prevent insulin from leaking out.
73
10.6 Self monitoring of Blood Glucose (SMBG)
Glucose meters play a central role in the management of diabetes particularly

for insulin- treated patients as insulin dose adjustment is reliant on SMBG. The
ADA consensus panel reported that up to 50% of SMBG determinations might
vary more than 20% from the true value4
The following table (Table 10.6) describes factors to be considered to assure the
accuracy of home glucose monitoring5
Table 10.6
1. Code on monitor matches code on glucose test strip vial

2. Glucose test strips stored in original container
3. Test strips within expiry date
4. Lateral side of finger pricked with puncture device
5. First drop of blood is wiped off, then hanging drop is tested
6. Blood is applied correctly to cover all of test strip
7. Strip is inserted at appropriate time
8. Monitor is cleaned weekly or as needed
9. Blood glucose value properly recorded
10. Control solution is used and control solution is within expiry date
11. Control values are within 10% of expected
74
REFERENCES
1. Grajower m et al. How Long Should Insulin Be Used Once a Vial Is Started?
Diabetes Care September 2003 26:2665-2669;
2. Insulin Storage in Europe: A comment to Grajower et al., Eli Lilly, and Novo
Nordisk Diabetes Care May 1, 2004 27:1225-1226.
3. Holcombe JH et al : How Long Should Insulin Be Used Once a Vial Is Started?

Response to Molitch. Diabetes Care May 2004 vol. 27 no. 5 1241-1242.
4. Heinemann L. et al. Variability of insulin absorption and insulin action.

Diabetes Technol Ther. 2002;4(5):673-82.
5. Self-monitoring of blood glucose. American Diabetes Association. Diabetes

Care 1990;13(Suppl 1):S41–6.
6. William A et al. Assuring the Accuracy of Home Glucose Monitoring. J Am

Board Fam Pract 2002; 15:1–6.
APPENDIX
Practical Guide to
Insulin Therapy in
76
APPENDIX
Carbohydrate Content of Common Malaysian Foods
Foods Serving Calories Carbohydrate Approx.

(kcal) content (g) Carbohydrate
Exchanges*
*1 carbohydrate
food exchange
= 15 g
Cooked rice 1 bowl (159g) 207 48 3

Roti canai 1 piece (95g) 301 46 3
Chappati 1 piece(100g) 300 47 3
Curry mee 1 bowl (450g) 549 55 4
Fried noodles
(mee/mee hoon) 1 plate (170g) 281 41 3
Bread
(white/wholemeal) 1 slice (30g) 70 15 1
Biscuits,
unsweetened 2 pieces (18g) 80 14 1
Curry puff 1 piece (40g) 128 17 >1
Potato 1 medium (90g) 90 16 1
Dhall (raw) ½ cup (98g) 98 64 4
Full cream milk 1 cup (250 ml) 187 18 1
Low fat milk 1 cup (250 ml) 131 12 1
Skim milk powder 4 tablespoon (28g) 100 16 1
Condensed milk,
sweetened 2 tablespoon (40g) 126 21 1.5
Apple/ orange 1 medium (114g) 40 9 <1
Banana
(pisang mas) 1 small (50g) 40 9 <1
Star fruit 1 medium (260g) 56 11 1
Langsat/ grapes/
longan 8 small (233 g) 52 12 1
Guava ½ fruit (100g) 50 11 1
Watermelon/
papaya/ pineapple 1 slice ( 160g) 56 11 1
Mango 1 small ( 100g) 50 11 1
77
INDEX
References are to page numbers within the booklet.

Page
Barriers
insulin absorption 71
insulin therapy 2; 11; 12
- solutions 12
patient barriers 11
provider barriers 12
- solutions 13
Basal bolus regimen

initiation and optimisation 28; 29
Basal insulin
basal bolus regimen 35
initiation and optimisation 24
intensification 33
basal plus regimen 34
premix regimen 36
Beta cells
progressive decline 5; 8
Diagnosis
role of insulin therapy
8
Exercise
benefits 58
insulin dose adjustment 59
Fasting and Ramadan

insulin therapy
- complications 60
- insulin dose adjustments 61
- severity of risk 60
Handling and storage

insulin 65; 66
78
INDEX

Page
Hypoglycaemia
clinical manifestations 49
insulin therapy 49
prevention 51
risk factors 50
severity 50
Injection site
practical issues 67
problems 53
Insulin
absorption 71
comparison of conventional insulin and insulin analogues 18; 19
effectiveness 6
handling and storage 65; 66
intensification 32
pen devices and needles 69
preparations 16
regimen 20
types 16
- pharmacokinetic profiles 17
Insulin absorption 71
affecting factors 71
Insulin analogues 18
Insulin injection
problems 72
Insulin regimen 20
Insulin resistance
progression of T2DM 6
79
INDEX

Page
Insulin therapy
barriers 2; 11; 12
- solutions 12; 13
current practice 2
implementation 23
intensification 32
monitoring 44
practical issues
- injection site 67
- insulin absorption 71
- insulin handling and storage 65; 66
- pen devices and needles 69
problems
- allergy and hypersensitivity 53
- hypoglycaemia 49
- injection site 53
- insulin injection 72
- weight gain 52
rationale 5; 6; 8
role 8
short-term use 8
special situations 56
- exercise 58
- fasting and Ramadan 60
- pregnancy 62
- travel 57
utilisation 2
Intensification
basal regimen 35
multiple premixed regimen 38
basal plus regimen 34
prandial regimen 40
premix regimen 36
Monitoring
continuous glucose monitoring 46
insulin therapy 44
self-monitoring of blood glucose 44
- accuracy 73
- glucose meters 73
Pen devices and needles 69

80
INDEX

Page
Pharmacokinetic profiles
insulin 17
Prandial insulin
initiation and optimisation 26; 27; 28
intensification 40
Pregnancy
insulin therapy 62
- management 62
- risks 62
Premixed insulins
addition of prandial insulin 39
intensification 33
multiple premixed regimen 38
Self-monitoring of blood glucose 44

accuracy 73
- glucose meters 73
insulin titration/adjustment 46
pattern management 46
timing in different insulin regimens 45
Sick days
hyperglycaemia 56
hypoglycaemia 56
‘sick days’ rules 56
Targets
glycaemic targets 43
Travel
insulin therapy
- long distance air travel 58
- preparations 57

diagnosis
- role of insulin therapy 8
- treatment and management 7
Weight gain
insulin therapy 52
81
GLOSSARY OF TERMS
BD Twice Daily (Bis Die)

BG Blood Glucose
BMI Body Mass Index
BP Blood Pressure
CHD Coronary Heart Disease
CVD Cardiovascular Disease
DCCT Diabetes Control and Complications Trial
DKA Diabetes Ketoacidosis
DM Diabetes Mellitus
DN Diabetic Nephropathy
DPP-4 Dipeptidyl peptidase-4
ECG Electrocardiogram
ED Erectile Dysfunction
FPG Fasting Plasma Glucose
GDM Gestational Diabetes Mellitus
GI Glycaemic Index
HbA1c Glycosylated Haemoglobin
HDL High Density Lipoprotein
IDF International Diabetes Federation
IFG Impaired Fasting Glucose
IGT Impaired Glucose Tolerance
LDL Low Density Lipoprotein
MNT Medical Nutrition Therapy
NCEP National Cholesterol Education Program
NPH Neutral Protamine Hagedorn
OAD Oral Anti-diabetic
OD Once Daily (Omni Die)
OGTT Oral Glucose Tolerance Test
OM On Morning (Omni Mane)
ON On Night (Omni Nocte)
PPAR-Y Peroxisome Proliferator-Activated Receptor-Gamma
PPG Post-prandial Plasma Glucose
RPG Random Plasma Glucose
S/C Subcutaneous
SMBG Self Monitoring Blood Glucose
SU Sulphonylurea
T1DM Type 1 Diabetes Mellitus
T2DM Type 2 Diabetes Mellitus
TDS Three Times Daily (Ter Die Sumendus)
TG Triglycerides
TZD Thiazolidinedione
UKPDS United Kingdom Prospective Diabetes Study
WC Waist Circumference
WHO World Health Organisation
82
ACKNOWLEDGEMENTS
The members of the working committee of this guide would like to

express their gratitude and appreciation to the following for their
contributions:
• Panel of external reviewers who reviewed the draft
• All those who have contributed directly or indirectly to the

development of this guide
SOURCES OF FUNDING
The development of this guide was supported by an

educational grant from sanofi-aventis
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Practical Guide To Insulin Therapy in Type 2 Diabetes

Book · January 2011

Hussein Zanariah Mas Md

SEE PROFILE SEE PROFILE

Mohd Noor Nurain

DiCARE View project

Asian diabetes population View project

The user has requested enhancement of the downloaded file.

SECTION 2 RATIONALE FOR INSULIN THERAPY IN

SECTION 3 BARRIERS TO INSULIN THERAPY 10

SECTION 4 INSULIN TYPES AND REGIMENS 15

SECTION 5 INSULIN INITIATION AND OPTIMISATION

SECTION 6 INSULIN INTENSIFICATION

SECTION 7 TARGETS AND MONITORING 42

SECTION 8 PROBLEMS WITH INSULIN THERAPY 48

SECTION 9 SPECIAL SITUATIONS 55

SECTION 10 PRACTICAL ISSUES 64

APPENDIX Carbohydrate counting 75

THE DIRECTOR GENERAL OF HEALTH OF MALAYSIA.

TAN SRI DATO’ SERI DR. HJ. MOHD ISMAIL MERICAN

The prevalence of diabetes in Malaysia continues to increase at an alarming rate from

Dr. Zanariah Hussein

MEMBERS (Alphabetical Order)

Dr. Foo Siew Hui Dr. Noor Lita Adam

Dr. Lim Siang Chin Dr. Nurain Mohd. Noor

Dr. Masni Mohamad Dr. Shamita Sharma

Dr. Mohamed Badrulnizam Long Bidin

Dr. Yong Sy Liang

Prof. Dato’ Paduka Dr. Wan Mohamad Wan Bebakar

Prof. Dr. Nor Azmi Kamaruddin

Dato. Dr. Santha Kumari

Dr. G. R. Letchuman Ramanathan

Dr. Feisul Idzwan Mustapha

Dr. Mastura Ismail

(The following external reviewers provided feedback on the draft)

Newly diagnosed DM & Type 2 DM

Normal Fasting / High Fasting / High Fasting /

Start Start Start Start Start

BASAL PLUS PREMIXED BD

* refers to insulin analogues only

A nationwide audit done by the Institute of Health Management (IHM) 3, MOH in

2. GR Letchumanan, P.K.Yap Muruga V, SP CHan, Oiyammal C, Loh KM, Ariza Z,

3. Haliza AM et al. Management of patients with type 2 diabetes mellitus in

4. Results of Diabcare(Malaysia) 2009. Novo Nordisk data on file.

5. Mafauzy M. Diabetes Control and Complications in Public Hospitals in

6. Juliana Chan et al. Multifaceted Determinants for Achieving Glycemic Control.

Years From Diagnosis

T2DM is a progressive disease characterised by worsening glycemia. There are

Numerous randomised controlled trials and large observational studies have

Diagnosis of Type 2 Diabetes

If HbA1c > 6.5%, If HbA1c ≤ 6.5%,

Introduce your patient to the eventual need for insulin so that it is

• Type 2 DM results from insufficient insulin secretion due to beta cell

• Over time beta cell function continues to deteriorate resulting in

• Elevated glucose levels can lead to diabetes complications, progression

• Treatment of elevated blood sugars slows the gradual worsening of

• Insulin injections will eventually be required to replace the body’s

(derived from Practical Guidance to Insulin Management – Primary Care Diabetes

1. UKPDS Group. UKPDS 16. Overview of 6 years’ therapy of type 2 diabetes-A

2. Holman RR. Assessing the potential for Alpha-glucosidase Inhibitors in

3. Vincent P et al. Glucolipotoxicity: Fuel Excess and Beta Cell dysfunction.

4. Maria Tzafos et al. Glucagon-Like Peptide-1 Analog and Insulin Combination