Prinsip pengobatan diabetes,

insulin dan OAD

 DIABETES MELLITUS
CLASSIFICATION
• TYPE1 DM
Sub classification :
 type1A (autoimmune) and
 type1B (idiopathic)
 fulminant type1 diabetes *
• TYPE2 DM
• OTHER SPECIFIC TYPE
• GDM (GESTATIONAL DIABETES MELLITUS)
ADA 1997, * Imagawa etal, NEJMed 342:301-307,2000
 diabetes management
• Healthy life style
• Exercise
• Dietary management
• Medicamentous (OAD, Insulin)
HISTORICAL BACK GROUND

• Before 1921 : starvation diet

• 1921 after : alterations in diet
• 1921 : KBH 20%, prot 10%, fat 70%
• 1950 : KBH 40%, prot 20%, fat 40%
• 1970 : KBH 45%, prot 20%, fat 35%
• 1986 : KBH up to 60%, prot 12-20%, fat
<30%
• 1994 : KBH >55%,prot 10-15%, fat <30%*
Adapted :Bailey CJ, UK 2004 *Saturated fat < 10%
MEMILIH MENU BERIMBANG !
 Aktivitas Fisik

• Pengeluaran kalori atau

energi terutama adalah
dari aktifitas fisik
• Pilihlah aktifitas fisik
yang sesuai dengan
usia dan waktu yang
ada
• Olahraga baru dapat
bermanfaat jika
dilakukan secara rutin
 Kriteria pengendalian DM

Baik Sedang
Buruk

GDP (mg/dl) 80-109 110-125

>126
GD2jpp (mg/dl) 80-144 145-179
>180
HbA1c (%) <6.5 6.5-8 >8
Kolesterol-T (mg/dl) <200 200-239
>240
Kol-LDL (mg/dl): <100 100-129
>130
Kol-HDL (mg/dl) >45
TG (mg/dl) <150 150-199 PERKENI 2002
>200
 DIABETES MELLITUS
CLASSIFICATION
• TYPE1 DM
Sub classification :
 type1A (autoimmune) and
 type1B (idiopathic)
 fulminant type1 diabetes *
• TYPE2 DM
• OTHER SPECIFIC TYPE
• GDM (GESTATIONAL DIABETES MELLITUS)
ADA 1997, * Imagawa etal, NEJMed 342:301-307,2000
The continuum of glucose intolerance

Type 2 Disability
Normal IGT Complications
Diabetes Death

Preclinical Clinical
state disease Complications

Primary Secondary Tertiary

prevention intervention intervention
 PRECIPITATING CONDITION

26 Live to Eat !
Dual defect of type 2 diabetes
 moving targets
Insulin Type 2 b-cell
Resistance Diabetes Dysfunction

b-cell Failure
Insulin
Concentration

Insulin
Resistance

Euglycaemia
Normal IGT ± Obesity Diagnosis of Progression of
(pre diabetes) type 2 diabetes type 2 diabetes
DeFronzo R et al. Diabetes Care 1992;15:318-68
 Natural History of Type 2 Diabetes

Insulin sensitivity Insulin secretion

Type 2
30% 50%
diabetes

50% IGT 70-100%

70% Impaired glucose 150%

metabolism
100% Normal glucose metabolism 100%

Diabetes Obes Metab 1999; 1(1): S1

 Intervention to effect better control
means fewer complications
EVERY 1%
reduction in HBA1C Reduced Risk*

Deaths from diabetes

Heart attacks

Microvascular complications
1%
Peripheral vascular disorders
*p<0.0001
UKPDS 35 BMJ 2000;321:405-412
 Treatment algorithm for type 2
diabetes
Aim Diet, exercise, health education

Sulphonylurea or metformin
Glucosidase Inhibitors
Glitinides
Thiazolidinediones
Oral combinations

Insulin

Improved control Insulin plus oral agents

Site and mode of action of oral
antidiabetic medications

Site of action MOA Agents

Insulin Sulphonylureas
secretion Other insulin
secretagogues

Glucose Biguanides
production Thiazolidinediones

Slow carbohydrate -glucosidase

-
digestion inhibitors

Peripheral insulin Thiazolidinediones

sensitivity (biguanides)

DeFronzo R. Ann Intern Med 1999;131:281-303

 Sites of Action of Current OAD
GLUCOSE ABSORPTION

INTESTINE

-glucosidase inhibitors
GLUCOSE
PRODUCTION PERIPHERAL GLUCOSE
UPTAKE & UTILIZATION
LIVER
Glucose
MUSCLE
Biguanides
Thiazolidinediones
ADIPOSE TISSUE

Thiazolidinediones
INSULIN SECRETION Biguanides
Sulphonylureas
Meglitinides
PANCREAS Modified: Ann Intern Med 1999;131:281
 Choice of agents in current use

Glipizide
Acarbose
Gliclazide
Miglitol
Glimepiride Sulphonylureas Voglibose
Glibenclamide

TZDs Metformin -glucosidase

inhibitors

Meglitinides
Rosiglitazone Repaglinide
Pioglitazone Nateglinide
 SULFONYLUREA
GENERASI I
 Tolbutamid GENERASI II
 Acetoheksamid  Glibornurid
 Tolazamid  Glipizid
 Carbutamid  Glisoxepid
 Glikodiasin  Glibenclamid
 Khlorpropamid  Gliclasid
 Gliquidon

GENERASI III
 Glinid (repaglinid dan nateglinid)
 Comparison between
1st generation SU Vs 2nd generation SU

First generation Second Generation

Lower binding affinity High affinity to SU
to SU receptor receptor
Higher dose Lower dose
Multiple dose Once daily

Higher incidence of Lower incidence of

hypoglycemia hypoglycemia
DeFronzo, Ralph A. Pharmacologic Therapy For Type 2 Diabetes Mellitus.
Ann Intern Med.1999;131:281-303
 Historical Algorithm of
Therapy for Type 2 Diabetes
Inadequate
nonpharmacologic
therapy

2 Oral 3 Oral
Oral agent agents agents

Add
insulin

Adapted from Mudaliar S et al. In: Ellenberg and Rifkin’s Diabetes Mellitus, 6th ed. New York, NY:
Appleton and Lange; 2003:531-557.
 Proposed Algorithm of
Therapy for Type 2 Diabetes
Inadequate non-
pharmacologic
therapy

• Severe symptoms
• Severe
hyperglycaemia Oral agent 2 Oral 3 Oral
• Ketosis agents agents
• Pregnancy

Add Insulin Earlier in the Algorithm

 Kriteria pengendalian DM

Baik Sedang
Buruk

GDP (mg/dl) 80-109 110-125

>126
GD2jpp (mg/dl) 80-144 145-179
>180
HbA1c (%) <6.5 6.5-8 >8
Kolesterol-T (mg/dl) <200 200-239
>240
Kol-LDL (mg/dl): <100 100-129
>130
Kol-HDL (mg/dl) >45
TG (mg/dl) <150 150-199 PERKENI 2002
>200
 BLOOD GLUCOSE TARGET
Parameter Normal* ADA ACE
FPG (mg/dl) < 110 90-130 < 110
PG-pp (mg/dl) < 140 < 180 < 140
PG-bed time < 120 110-150 -
(mg/dl)
HbA1C (%) 4-6 <7 < 6.5
* normal individuals
ADA : American Diabetes Association,
ACE : American college of Endocrinologist
Glyco Hb ranges, estimated daily
BG values, and interpretation
Glyco Hb (%) Averages BG interpretation
levels (mg%)

5.4-7.4 <120 Non DM

7.4-8.5 120-150 Excellent
8.6-10.5 150-200 Good
10.6-13.0 200-300 FaIr
>13.0 >300 Poor

Krall LP, Beaser RS, Joslin Diabetes Manual, 12th edition, 1988
 Target BG levels
Time Ideal normal Target levels
level (mg%) (mg%)
Before breakfst 70-105 70-120
Before Lunch, 70-110 70-140
Supper, Bed
time snack

1 hrs after M <160 <180

2 hrs after M <120 <150
Krall LP, Beaser RS, Joslin diabetes manual, 12th edition, 1998
BLOOD GLUCOSE MONITORING IN OUT
PATIENTS AND IN HOSPITALS
• Clear administrative responsibilities of the
procedure
• A well defined policy / procedure manual
• A training program for those personal
(pat,fam,nurse) doing the testing
• Quality control procedures
• Regularly schedulled equipment
maintenance
ADA, clinical practice recom, 2003. Diabetes Care 26(suppl 1) : S119, 2003
 WHEN, HOW, WHY
WHEN
 Fluctuation of Blood glucose (meal, sick
day, stress, exercise)
 Risk of hypoglicemia (intensive Ins th/, meal, exercise)
 Blood glucose in critically ill patients (stress
hormone)
HOW
 Urine testing
 Peripheral blood / capillary blood
WHY
 Avoid harmfull effect of poor diabetic control
Terima kasih
Physiological Insulin Secretion Profile

75
Breakfast Lunch Dinner
Plasma Insulin µU/ml)

50

25

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 Risk of hypoglicemia
• Intensive insulin therapy
• Related with meal,
• Related with Exercise
activities
 Urine testing
• Aims : glucose, protein and keton
• How ?
 Glucose testing
 copper test (fehling, benedict,
clinitest, clinistix)
 enzymatic test (glucotest, diastix)
 Protein (micral tst, combur test, etc)
 Keton (acetest)
• When ?
• OUT OF DATE ?
 Peripheral blood / capillary
blood

• Hospital monitoring
 Blood glucose in critically ill patients,
perioperative setting
• Self monitoring (out patient setting)
Self monitoring of BG control
Indications
 T1 and T2DM (insulin treated patients)
Aims
 To full fill the target of control  good,
fair / acceptable BG control)
 Avoid hypoglicemia

Adcapted : Diabetes in the New Millenmium, 1999

 EVOLUTION OF INSULIN REGIMEN
Bolus regimens
1920s, 1st insulin
Short-acting, acid pH
Only bolus regimen
Breakfast Lunch Dinner No basal insulin
Plasma Insulin

Actrapid Actrapid Actrapid

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 Basal/Bolus regimens
1940s,
1st long-acting insulin
NPH, Neutral pH
Basal-bolus possible
Breakfast Lunch Dinner
Ideal,
but too many injections
Plasma Insulin

Actrapid Actrapid Actrapid

Insulatard Insulatard

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 Split-Mixed regimens
1961, 1st combination
ActRapid, neutral pH
Breakfast Lunch Dinner Split-mix became possible
Plasma Insulin

Actrapid + Insulatard Actrapid + Insulatard

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 Premix regimens
1964,
Fixed dose combination
Mixtard
Breakfast Lunch Dinner Premix becomes choice
Plasma Insulin

Mixtard Mixtard
(30% reg + 70% intermediate) (30% reg + 70% intermediate)

4:00 8:00 12:00 16:00 20:00 24:00 4:00 8:00

Time
 Summary: How the regimens evolved?
1964,
Fixed dose regimens
Premix combination
Mixtard
Premix becomes choice

1961, 1st combination

Split-mixneutral
ActRapid, regimens
pH
Split-mix became possible
1940s,
1st long-acting insulin
NPH, Neutralregimens
Basal-Bolus pH
Basal-bolus possible
Ideal,
but too many injections
1920s, 1st insulin
Short-acting, acid pH
Bolus regimens
Only bolus regimen
No basal insulin
 INSULIN ADMINISTRATION
• Obtain from Pork, Human or recombinant DNA tech.
or chem modif. of pork insulin.
• Available in : rapid,short, intermediate and long
acting (injected sparetely or mixed)
• Rapid ins. analog : lispro, aspart.
• Short actng ins : regular ins, Actrapid,Humolin R
• Intermediate : lente, NPH
• Long acting : ultra lente, insulin glargine.
• Mixt tipe : act/monotard (30:70), NPH/reguler (70/30,
50/50), NPL/Lispro (25/75).
• Concentration : U-100, U-500, U-10

ADA, Diabetes Care 26(suppl 1),2003

 Injection device development in the
80s and 90s has addressed these
issues
1920s
More insulin pen introductions 1925
in 1990s
the…

1989 From syringes to safe

and convenient portable
1985pens with insulin
cartridges 1960
 Meeting individual needs and
lifestyles
• Multiple colours and needles - and
selections for children, the elderly
and the advanced users
 Advances in alternative ways of insulin
administration

Transdermal insulin delivery

Continuous subcutaneous
insulin infusion (CSII)

Oral insulin delivery

Pulmonary insulin delivery Buccal insulin delivery

 Terima kasih

PURE PARHYANGAN AGUNG GUNUNG SALAK (Oct, 2005)