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  1. Diabetes Mellitusan overview Aly A. Abdel-Rahim, MD

  2. Diabetes is a disorder caused by the presence of too much glucose in the blood. A first depiction of this “sugar disease” was described in the “Ebers Papyrus”, a papyrus sold to the German Egyptologist Georg Moritz Ebers in 1872. It was said to have been found close to a mummy in the tomb of Thebes and appears to have been written between 3000 and 1500 BC.

  3. History • Reference to diabetes was made 1550 BC. • In the 2nd Century AD, Aretaeus gave an excellent description of diabetes. • Thomas Willis in the 17th Century detected the sweet test of urine. • Mathew in the 18th Century showed that the sugar in urine comes from the blood.

  4. History • Minkowski and Von Mering discovered that disease of the pancreas is responsible for diabetes to develop in the 19th century. • In the 19th century treatment of diabetes was confined to food regulation which reduced urination but did not prevent wasting and complications.

  5. History • In the second half of the 19th Century, Paul Langerhans, a German student, identified clusters of cells within the pancreas responsible for the production on glucose lowering substance. “islets of Langerhans”. • Insulin: in Latin insula= island. So the name was coined before the hormone was discovered.

  6. History • Banting and Best “a student” worked in McLeod's labs in Toronto. • In 1921they made the exocrine cells atrophy by ligation of the pancreatic duct. • They made aqueous extracts of the remaining tissue keeping it cold and filtered it. • The extract was injected into a diabetic dog on 30 July 1921.

  7. History • They convinced themselves that they had discovered the active pancreatic hormone which normalizes the blood sugar.

  8. History • The first person to be treated with insulin was Leonard Thompson (1908-1935). The first injection was in 11 January 1922

  9. History: Noble Prize 1923 Banting McLeod Best Collip

  10. Definition of diabetes • A syndrome of chronic hyperglycaemia with other metabolic abnormalities together with micro and macro-vascular complications.

  11. What is wrong with diabetes • Insulin deficiency • Insulin resistance Hyperglycaemia

  12. Classification of diabetes • Type 1DM • Type 2DM • IFG: impaired fasting glycaemia • IGT: impaired glucose tolerance • GDM: Gestational diabetes mellitus • Secondary DM.

  13. Criteria of diagnosis • FBS > 125. • PP > 200 • OGTT. normal: • FBS <100 • PP <140

  14. T1DM • Usually in young age • Characterized by absolute insulin deficiency. • Increased catabolism and liability to ketosis. • Stormy presentation. • must be treated with insulin.

  15. T2DM • Usually in older age. • Relative insulin deficiency. • Increased insulin resistance. • Can be treated with OHA or insulin. • Slow onset, less likely to develop ketosis. • May present with complications.

  16. MODY Maturity onset diabetes of the youth • A special type of diabetes similar to type 2 diabetes but develop in young age groups. • Increased prevalence worldwide. • Associated with increased childhood obesity.

  17. Diabetes related to drugs • Glucocorticoids • Diazoxide. • Thiazides. • Phyention • Pentamidine

  18. GDM Gestational diabetes mellitus • Diabetes discovered for the first time during pregnancy. • Every pregnant lady should be screened. • Usually disappears after labor. • Increased risk to develop T2DM later in life.

  19. Diabetes is a pandemic

  20. Prevalence of diabetes in the EMME region

  21. Prevalence of IGT in the EMME region

  22. Prevalence of DM & IGT by region

  23. Estimated 10 prevalence of diabetes

  24. Estimated 10 top number of diabetes patients

  25. Social profile related to diabetes in Egypt • with an average income per person of $1,490 in 2001, fighting poverty remains a substantial challenge. • In it dropped to $1.390 in 2003 and then $1.310 in 2004. * • People living under poverty line (<1 $/day) 3.7% *WHO statistics 2005

  26. Social profile related to diabetes in Egypt • Life expectancy is 69.1 years. • National poverty rate (% of population) 16.7 . • Child malnutrition, weight for age (% of under 5) 4.0 in 2003 increased to 8.6 2004. Source: World Development Indicators database, August 2005

  27. Prevalence of diabetes in Egypt • Herman : 9.3% above 20y of age. • Arab 4.3% above 20y of age. • Why the difference ??? region e.g.: desert and Nubians.

  28. Prevalence of diabetes in Egypt • Herman : 9.3% above 20y of age. • Arab 4.3% above 20y of age. • Why the difference ??? region e.g.: desert and Nubians.

  29. Diagnosis • How to diagnose diabetes: • Signs and symptoms • Blood glucose test • OGTT • HbA1c

  30. Diagnosis • Most people are diagnosed with diabetes when they are suspected to have symptoms of polyurea, polydepsia, fatigue, loss of weight. • This is confirmed by fasting or PP blood glucose. • In case of doubt OGTT may be done. • Urine testing should not be used in diagnosis.

  31. Diagnosis • Peers and medical ‘advisors’ should be aware of the following: • T1DM & T2DM are two distinct diseases. • T1DM is stormy at presentation, delay in diagnosis can be disastrous. • Among the presentations of T1DM could be some non-specific symptoms like vomiting, abdominal pain….

  32. Diagnosis • T2DM may present with late symptoms, like numpness, disturbed vision, generalized oedema. • Patients with hypertension, dyslipidaemia, MI and family history of diabetes are very likely to develop T2DM.

  33. Pathophysiology of T1DM Absence of insulin secretion Failure to use glucose as a fuel Hyperglycaemia & using fat Ketosis

  34. Pathophysiology of T1DM • Possible contributing factors: • Autoimmune disease. • HLA typing • Viruses • chemicals

  35. Pathophysiology of T1DM • Remission. • The honeymoon period

  36. Pathophysiology of T2DM Insulin resistance hyperinsulinaemia Relative hypoinsulinaemia Hyperglycaemia, dyslipidaemia, atherosclerosis, HTN

  37. Pathophysiology of T2DM • Causes of insulin resistance: • Hereditary. • Decreased glucose transporters. • Decreased insulin receptors • Post receptor mechanisms • Chemical mediators e.g. TNFα

  38. Pathophysiology of T2DM • Loss of first phase of insulin secretion. • Delayed insulin release.

  39. Insulin

  40. Insulin

  41. Insulin

  42. Insulin

  43. Insulin • Action of insulin: • On glucose metabolism • On amino acid metabolism • On lipid metabolism

  44. Insulin • Short acting

  45. Insulin • Intermediate acting

  46. Insulin • Peak less insulin • Act for 24 hours no peak

  47. Insulin • Premixed insulin

  48. Insulin • Preparation of human insulin: