1. UPDATE ON DIABETES AND INSULIN THERAPY BY Dr. M. SYED SULAIMAN. M
UPDATE ON DIABETES AND INSULIN THERAPY BY Dr.M.SYED SULAIMAN.M.D; PHYSICIAN & DIABETOLOGIST

2. DIABETES ENVIRONMENT IN INDIA
Diabetes is no more an epidemic, it
is a PANDEMIC. Diabetes related complications pose greatest risk of morbidity and mortality.

3. No
COUNTRY
2000
2030 1
INDIA
31.7
79.4 2
CHINA
20.8
42.3 3
U.S.A
17.7
30.3 4
INDONESIA
8.4
21.3 5
JAPAN
6.8
PAKISTAN
13.9 6
5.2
BRAZIL
11.3 7
U.S.S.R
4.6
BANGLADESH
11.1 8
8.9 9
ITALY
4.3
PHLIPPINES
7.8 10
BANGLADEH
3.2
EGYPT
6.7

4. BURDEN OF DIABETES : MORBIDITY
DIABETIC RETINOPATHY
#1 Cause of blindness in working age adults
DIABETIC NEPHROPATHY
#1 Cause of ESRD
DIABETIC NEUROPATHY AMPUTATIONS
#1 Cause of non-traumatic amputations of lower
Extremity.
DIABETIC VASCULAR DISEASE
2 to 6 fold higher risk of CVD

5. DEFINITION
Diabetes Mellitus is a group of metabolic diseases characterized by Hyperglycemia resulting from defects in Insulin secretion, Insulin action, or both.

6. ETIOLOGIC CLASSIFICATION OF
DIABETES MELLITUS
1.Type 1 Diabetes
Immune mediated
Idiopathic
2.Type 2 Diabetes

7. 3.Other specific types: a. Genetic defects of b-cell function
b. Genetic defects in insulin action
c. Disease of exocrine pancreas
d. Endocrinopathies
e. Drug/chemical induced
f. Infection
g. Uncommon immune mediated
h. Other Genetic Syndromes
4. GESTATIONAL DIABETES MELLITUS(GDM)

8. IMPAIRED INSULIN SECRETION &
ETIOLOGY OF TYPE 2 DM
IMPAIRED INSULIN SECRETION &
INSULIN RESISTANCE
GENES & ENVIRONMENT
GENES AND ENVIRONMENT
IMPAIRED INSULIN
SECRETION
IMPAIRED INSULIN
SECRETION +
INSULIN RESISTANCE
INSULIN RESISTANCE
IMPAIRED GLUCOSE
TOLERANCE
IMPAIRED GLUCOSE
TOLERANCE
TYPE 2 DM

9. IFG -Impaired Fasting Glucose IGT -Impaired Glucose Tolerance
DIAGNOSTIC CRITERIA OF DIABETES
NORMAL
IFG/IGT
DIABETES
FPG
<100
≥100<126
≥126
2hrPost Glucose Load
<140
≥140<200
≥ 200
IFG -Impaired Fasting Glucose
IGT -Impaired Glucose Tolerance

10. What is pre diabetes?
Abnormal blood glucose Values which is clearly Above the normal values but less than the Values diagnostic of Diabetes
[IMPAIRED GLUCOSE METABOLISM]

11. MAJOR RISK FACTORS FOR TYPE 2 DM
1. Age>45
2. Race / Ethnicity (Asian / Asian
American / Hispanics / etc)
3. Obesity (>30kg/m)
4. Family h/o Diabetes
5. Sedentary lifestyle
6. h/o GDM or delivered a baby
weighing>4.5kg
7. PCOS

12. ACUTE METABOLIC COMPLICATIONS OF DIABETES MELLITUS
A.) DIABETIC KETOACIDOSIS
B) HYPEROSMOLAR HYPERLYCEMIC STATE
C) HYPOGLEMIA

13. Diabetes Mellitus and chronic complications
Diabetes is a vascular disease
Affects both small and medium sized arteries (micro vascular &macro vascular)

14. Chronic complications
MICRO VASCULAR
Retinopathy
Nephropathy
Neuropathy
Macrovascular
CVD
CAD
PVD

15. MANAGEMENT Diet Exercise Insulin Oral Antidiabetic Drugs
DPP 4 Inhibitors
Amylin Analogues

16. ORAL ANTI DIABETIC DRUGS
Secretogauges
a) Sulphonylurias
b) Non sulphonylurias
Biguanides
Alpha Glucosidase Inhibitors( A G I )
Thiozolidinediones
DPP 4 Inhibitors
Amylin Analogues
Exenatide

17. SECRETOGOUGES Sulphonyluria Groups First Generation SU 1.Tolbutamide
2.Chlorpropamide
Second Generation SU
1.Glibenclamide(Daonil,Euglucon)
2.Glipizide(Glynase,Dibizide)
3.Gliclazide(Diamicron,Reclide)
4.Glimipride(Amaryl,Glipride,Glimer)

18. SECRETOGOGUES
Currently available secretogogues stimulate Insulin secretion by causing closure of ATP dependent Potassium channel in Islet β cells.

19. NON SU SECRETOGOGUES
Meglitinides
Repaglinide(Novonorm)

20. INSULIN SENSITIZERS
Agents from this group enhances the effect of endogenous Insulin.
A reduction in Insulin resistance at each and every stage of diabetes will improve Glucose metabolism.
Biguanide(Metformin),Thiozolidinediones(PIO,ROSI)

21. BIGUANIDES METFORMIN(Glyciphage,Glycomet).
Primary site of action:Liver.
Reduces hepatic glucose output.
Reduce fasting hyperglycemia.

22. THIOZOLIDINEDIONES Troglitazone Rosiglitazone(Rezult,Enselin)
Pioglitazone(Pioz,Pioglit)
Primary site of action : Adipose
Cells, Skeletal muscles.

23. AGI Acarbose(Glucobay,Acarb) Miglitol(Misobit,Mignor)
Voglibose(Volibo,Volix)
Blocks alpha glucosidase enzyme
Targets postprandial hyperglycemia

24. DPP 4 Inhibitors (Dipeptidyl Pepsidase 4)
Nateglinide
Citagliptin
Vidagliptin
DPP 4 Inhibits GLP 1.Thus extends Insulin action.
Improves satiety,Increases β cell production,Inhibits β cell apoptosis delays gastric emptying,stimulate Insulin release

25. AMYLIN ANALOGUES
Pramlintide

26. INSULIN First hormone to be Discovered Introduced in clinical practice
Structurally characterized
Synthesized – chemically
Biosynthesized – by rDNA technology

27. Insulin – Definitive Therapy for Diabetes
In diabetes there is impaired insulin secretion and impaired insulin action
Exogenously administered Insulin can overcome both defects
Thus insulin is the definitive therapy for all types of diabetes

28. INSULIN ABSOLUTE INDICATIONS
Regular Use
Type 1 Diabetes Patients
Type 2 Diabetes Patients with OHA failure
- Primary
- Secondary
Intermittent Use
Type 2 diabetes patients during
- major surgery
- pregnancy, labour and delivery
- myocardial infarction
- acute infections
- acute metabolic crisis like hyperosmolar non
ketotic coma and lactic acidosis
Gestational diabetesmellitus

29. Type 1 DM Insulin Therapy
Initiating insulin therapy in uncomplicated ambulatory Type 1 patients
Initiating insulin therapy in ill patients with altered sensorium

30. Type 1 DM Insulin Therapy : Initiation
In uncomplicated ambulatory Type 1 patients
Patients should preferably be admitted to hospital
Initiate with short-acting insulin [0.5 IU/Kg body weight per day] divided over 3 doses/day given pre-meal; subcutaneously

31. Type 1 DM Insulin Therapy : Initiation
If hospital admission is not possible, close continuous monitoring of the patient is necessary
After adequate control is obtained with the above treatment a minimum of twice daily regimen with a short and intermediate-acting insulin may be given as per individual patient requirement

32. ACTION PROFILE OF INSULIN
Type
Onset
Peak
Duration
Rapid-Acting Analogues (Aspart, Lyspro)
min
1-1.5 h
4-5 h

34. ACTION PROFILE OF INSULIN
Type
Onset
Peak
Duration
Short-Acting (Regular)
30-60 min
2-4 h
6-8 h

36. ACTION PROFILE OF INSULIN
Type
Onset
Peak
Duration
Intermediate-Acting(Basal)
NPH
2-5 h
6-8 h
14-18 h

38. ACTION PROFILE OF INSULIN
Type
Onset
Peak
Duration
Pre-Mixed (30/70,50/50
Regular/NPH)
30 min
2-8 h
14-18 h

40. ACTION PROFILE OF INSULIN
Type
Onset
Peak
Duration
Long-Acting Analogue
(Detemir,Glargine)
2-3 h
No peak
24-30 h

42. TYPES OF INSULINS Type Formulation preparation Onset (hr) Max.
effect (hr)
Duration (hr)
Short
Regular
H.Actrapid Actrapid
0.5
1-3 8
Intermediate
- NPH (Neutral protamine Hagedom)/ Isophane
H.Insulatard Insulatard
1.5
4-12 24
- Insulin Zinc Suspension/ Lente
H.Monotard Lentard
2.5
7-15
Biphasic
Regular (30%) + NPH (70%)
H.Mixtard Mixtard
2-8

43. REGIMENS Should maintain normal blood glucose levels (Normoglycemia)
Mimic normal physiological profile
Regimens vary in Type 1 and type 2 diabetes because of different pathophysiology

45. INSULIN REGIMENS – Type 1 Diabetes
Insulin secretion totally absent
Insulin administration tailored to match demand
(food intake)
Need for multiple injections
Popular Regimens
* Basal Bolus: Ideal but difficult to implement
* Split mix therapy: Popular regimen; Patients find mixing insulins difficult
Premixed Insulins: Most popular regimen world- wide and in India
Right mix of compliance and control
Insulin required
i.u/kg body weight/day
- Regimen depends on blood glucose profiles

46. BASAL BOLUS THERAPY At least four injections/day
Intermediate injection at bedtime
soluble insulin before breakfast, lunch and dinner
Regular blood monitoring must
Requires highly motivated patient

48. SPLIT MIX REGIMENS Two injections (intermediate + soluble) per day
before breakfast and before bedtime
Proportion/dosage of insulin titrated based on blood glucose profile
Mixing insulin is tedious and problematic

51. A. COMPLIANCE Defective insulin regimen
Incorrect technique of mixing and measuring
Inconsistent eating and exercise habits
Omission of insulin during inter current illness
Lack of awareness about diabetes at the beginning and during the course of illness
Emotional and psychological disturbance

52. B. CHANGE IN INSULIN REQUIREMENTS
Inactivity
Weight gain / Loss
Pregnancy and Post delivery phase
Change in the exercise pattern
Change in the food habits
Stress period

53. PREMIXED REGIMENS – Human Mixtard
Very Popular regimen
Most popular World-wide & in India
Right balance of convenience and control
Improves compliance
Popular schedule is
2/3rd daily dose half an hour before breakfast
1/3rd daily dose half an hour before dinner

54. Insulin Therapy for Type 2 DM
Basal Insulin Supplementation: Bedtime NPH
Suppresses basal hepatic production
Reduces fasting plasma glucose
Generally used in combination with OHA
Helps initiate the patient on insulin therapy with Insulatard NovoLet

56. Guidelines for Initiating Insulin
Alone or in combination with an OHA
0.2 units/kg body wt./day of intermediate acting insulin e.g. Insulatard NovoLet
Increase dose by 2-4 u every 3-4 days if necessary. If requirement exceeds u, split the dose into two daily : 2/3 before breakfast, 1/3 before dinner
If postprandial glucose levels are high introduce short acting insulin in 30:70 or 50:50 ratio

57. Early Insulin Initiation
Is therefore beneficial in:
Providing better control of hyperglycemia
Reversing other metabolic defects
Controlling inflammation which may initiate and aggravate development and progression of diabetes and diabetes-induced tissue damage
Preserving beta cell function and thus helping maintain better glycemic control in the long-term
Should be done when it can be useful to the patient

58. FACTORS AFFECTING INSULIN PHARMAKOKINETICS
Injection site
Exercise
Depth of injection
Insulin source
Potency
Insulin antibodies

59. Injection Site The absorption varies with change of area
Rotation of site within the same area
Short Acting - ABDOMEN - If rapid action desired
Suspensions - THIGH - for longer action
Random rotation of the site should be avoided

60. Rotation of Site in a given area
Blood flow
Temperature
Heavy massage in the injected area

61. Exercise
Exercise following insulin injection increases the amount of insulin absorbed as well as the rate at which it is absorbed
Exercise increases the peripheral glucose utilisation by increasing the insulin sensitivity

62. Depth of injection IM Vs SC inj
Absorbed faster with IM injections
IM injections are not recommended for routine use
Useful only in patients with subcutaneous insulin degradation or resistance
IM injections are more painful
SC is therefore ideal
Soluble [ Human Actrapid ] can be given IV during surgery and diabetic emergencies

63. Source of insulin Human Insulin is absorbed quicker
Bovine Insulin is the slowest
Porcine is absorbed little slower than Human
Auxiliary Substances
Preservative - phenol, metacresol
Retarding Agent – protamine, zinc
Water as solvent

64. Insulin Antibodies
Circulating antibodies and exogenous insulin bind to form insulin antibody complex
The antibody bound insulin may produce a delayed effect at an unexpected time
Resulting from Reduced absorption , Delayed clearance

65. Thankyou