1. Etiopathogenesis of Diabetes Mellitus
Dr Shahjada Selim Assistant Professor Department of Endocrinology Bangabandhu Sheikh Mujib Medical University, Dhaka

2. Etiopathogenesis of diabetes by Dr Shahjada Selim
Diabetes mellitus
Definition:
Diabetes mellitus (DM) is a state of
chronic hyperglycemia due to defect
in insulin secretion and or its action.
19 June 2018
Etiopathogenesis of diabetes by Dr Shahjada Selim

3. Diabetes: A global emergency

4. Diabetes around the world

5. Diabetes around the world

6. Diabetes around the world

7. Cell types in pancreatic islets of Langerhans
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Etiopathogenesis of diabetes by Dr Shahjada Selim

8. Type of cells Quantity of cells (%) Secreted hormone
Α (α)
20 – 25
Glucagon, GLP-1,
GLP-2
Β (β)
70 – 80
Insulin, amylin
D (δ)
5 – 15
somatostatin
F (РР)
5 - 10
pancreatic polypeptide
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Etiopathogenesis of diabetes by Dr Shahjada Selim

9. Etiopathogenesis of diabetes by Dr Shahjada Selim
Insulin
Molecular weight of this peptic substance is 6000.
It consists of 51 aminoacidic parts from 16 different aminoacids
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Etiopathogenesis of diabetes by Dr Shahjada Selim

10. Etiopathogenesis of diabetes by Dr Shahjada Selim
Insulin
The most important biologic stimulator of insulin secretion is glucose
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Etiopathogenesis of diabetes by Dr Shahjada Selim

11. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

12. Etiopathogenesis of diabetes by Dr Shahjada Selim
Insulin is an anabolic hormone (promotes the synthesis of carbohydrates, proteins, lipids and nucleic acids). The most important target organs for insulin action are:
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Etiopathogenesis of diabetes by Dr Shahjada Selim

13. Insulin insufficiency
Absolute
1. Genetic disorders
2. Autoimmune damaging of β-cells
3. Damaged caused by virusessuch as mumps, or Coxsackie B4
4. Toxic influence on β-cells
5. Diseases of pancreatic gland
Relative
β-cells
Insulin transport
Receptors (tissue insensitivity)
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Etiopathogenesis of diabetes by Dr Shahjada Selim

14. Etiologic classification of DM (1999)
I. Type 1 of DM (destruction of β-cells which mostly leads to absolute insulin insufficiency):
autoimmune; idiopathic.
II. Type 2 of DM (resistance to insulin and relative insulin insufficiency or defect of insulin secretion with or without resistance to insulin).
III. Other specific types:
genetic defects of β-cells function;
genetic defects of insulin action;
pancreatic diseases (chronic pancreatitis; trauma, pancreatectomy; tumor of pancreatic gland; fibrocalculosis; hemochromatosis);
endocrine disease (acromegaly, thyrotoxicosis, Cushing’s syndrome);
drug exposures ;
infections and others.
IV. Gestation diabetes.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

15. Etiopathogenesis of diabetes by Dr Shahjada Selim
Type 1
is characterized by pancreatic islet beta -cell destruction and absolute deficiency.
The onset of the disease is generally in youth, but it can occur at any age. Patients have dependence on daily insulin administration for survival.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

16. Pathogenesis of type 1 DM
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Etiopathogenesis of diabetes by Dr Shahjada Selim

17. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

18. Type 2, or noninsulin-dependent diabetes mellitus (NIDDM)
Type 2 is the most common form of diabetes, accounting for 95 – 90 % of the diabetic population. Most investigators agree that genetic factors underlie Type 2 DM, but it is probably not caused by defects at a single gene locus.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

19. Pathophysiology of type 2 diabetes
Skeletal
Muscle
GI tract
Pancreas
Adipocyte
Muscle
α cells
 cells
Incretin deficiency
Altered fat metabolism
Hyperglucagonaemia
↑ hepatic sensitivity to glucagon
INSULIN RESISTANCE
INADEQUATE INSULIN SECRETION
↑ HEPATIC GLUCOSE PRODUCTION
CNS
Kidney
↑ BLOOD GLUCOSE
Enhanced glucose reabsorption
CNS, central nervous system; GI, gastrointestinal; T2DM, type 2 diabetes mellitus
Cernea S & Raz I. Diabetes Care 2011;34(suppl 2):S264–S271

20. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

21. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

22. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

23. Pathogenetic and clinical difference of type I and type II DM
Signs
Type 1
Type 2 1
Beginning of disease
Acute
Gradual 2
Duration
Labile
Stable 3
Ketosis, ketoacidosis
Often develops
Rarely develops 4
Body weight
Decreased or normal
Obesity in % of patients 5
Age
Young (under 35)
Old, middle
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Etiopathogenesis of diabetes by Dr Shahjada Selim

24. Pathogenetic and clinical difference of type I and type II DM
Signs
Type 1
Type 2 6
Treatment
Insulin, diet
Diet, drugs, insulin 7
Degrees of severity
Middle, hard
Mild, middle, hard 8
Connection with HLA-system
Present
Absent 9
Level of insulin and C-peptide
Decreased or
absent
Frequently normal level
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Etiopathogenesis of diabetes by Dr Shahjada Selim

25. Pathogenetic and clinical difference of type I and type II DM
Signs
Type 1
Type 2
10.
Antibodies
to β-cells
Present in % of patients on first week, month
Absent
11.
Late
complications
Microangiopathies
Macroangiopathies
12.
Mortality
Less than 10%
More than 20%
13.
Spreading
10-20%
80-90%
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Etiopathogenesis of diabetes by Dr Shahjada Selim

26. Etiopathogenesis of diabetes by Dr Shahjada Selim
Pathophysiology of DM
Defective polymorphonuclear function → infection ↑
Hyperglycemia → glucosurea → polyurea → dehydration
Insulin lack ↓
Hyperosmolality
Proteolysis → weight loss → muscle wasting → polyphagia
Lipolysis → free fatty acid release → ketosis → acidosis
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Etiopathogenesis of diabetes by Dr Shahjada Selim

27. Stages of DM development
I. Prediabetes (risk factors or predispose factors).
II. Impaired glucose tolerance (latent DM).
III. Clinical manifestation of DM.
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Etiopathogenesis of diabetes by Dr Shahjada Selim

28. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

29. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

30. Insulin Secretion in Non-Diabetics
and Type 2 Diabetics
Clock Time (Hours)
06:00
Normal
Type 2 DM
10:00
14:00
18:00
22:00
02:00
800
700
600
500
400
300
200
100
Insulin Secretion (pmol/min)
O'MEARA et al. Am. J. Medicine, 1990;89
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Etiopathogenesis of diabetes by Dr Shahjada Selim

31. Prediabetes (risk factors or predispose factors)
obesity
positive family history of DM
persons which were born with weight more than 4,0 kg
women who had-children with weight more than 4kg, abortions and dead child in anamnesis;
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Etiopathogenesis of diabetes by Dr Shahjada Selim

32. Prediabetes (risk factors or predispose factors)
persons with: atherosclerosis, hypertension
auto-immune diseases
Furunculosis
rubella, mumps, Coxsackie virus, infectious hepatitis, cytomegalovirus, infection mononucleosis;
endocrine disorders
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Etiopathogenesis of diabetes by Dr Shahjada Selim

33. Etiopathogenesis of diabetes by Dr Shahjada Selim
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Etiopathogenesis of diabetes by Dr Shahjada Selim

34. Thank you for attention!
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Etiopathogenesis of diabetes by Dr Shahjada Selim