Etiopathogenesis of Diabetes Mellitus Dr Shahjada Selim Assistant Professor Department of Endocrinology Bangabandhu Sheikh Mujib Medical University, Dhaka Email: selimshahjada@gmail.com, info@shahjadaselim.com
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
Diabetes: A global emergency
Diabetes around the world
Diabetes around the world
Diabetes around the world
Cell types in pancreatic islets of Langerhans 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim Insulin The most important biologic stimulator of insulin secretion is glucose 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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: 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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) 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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. 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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. 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Pathogenesis of type 1 DM 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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. 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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 80-90 % of patients 5 Age Young (under 35) Old, middle 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Pathogenetic and clinical difference of type I and type II DM Signs Type 1 Type 2 10. Antibodies to β-cells Present in 80-90 % 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% 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Stages of DM development I. Prediabetes (risk factors or predispose factors). II. Impaired glucose tolerance (latent DM). III. Clinical manifestation of DM. 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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; 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
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 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Etiopathogenesis of diabetes by Dr Shahjada Selim 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim
Thank you for attention! 19 June 2018 Etiopathogenesis of diabetes by Dr Shahjada Selim