Pathology lectures for 4th year medical students on Diabetes

1. Always do your best. What you plant now, you will harvest later.- - OgMandino

2. CPC 3.2: Ms. ML, 18y, Thrush. Recurrent thrush*, boils*, tired*, Obese*, junk food, no exercise*, polyuria, polydipsia* , Abd. Striae*, Mom DM2*, smoker, social drinker. Dipstick: Nitrate +, WCC 3+, Blood 2+, Prot. 2+, Glucose 2+ MSU: Ecoli >108, swab: Candida 4+, RBGL 35. ? Key points: ? Differential Diagnosis: Thrush, UTI, STI, Pregn, DM ? Further questions:

3. CPC 3.1: Molly 15y.. Wee problem. Molly is a 15 year old Y10 student comes to ED with her Aunty Ada, community health worker. Ada says Molly has ‘wee’ problem. Molly : ‘I’m going to the toilet often to pass wee and it is sore and itchy afterwards’ ? Key points: ? Differential Diagnosis: ? Further questions ? DM type ? How to confirm Investigations? ? Complications Prognosis? ? Management

4. ?Pathogenesis: “recurrent multisite infections” Associated AIDS Hyperglycemia Ischemia Immunodeficiency Multifactorial

5. Specific features for diagnosis of DM2? On & off for long time. Always drinking. Obesity. Recurrent boils. Mom has DM2

6. Miss ML: Most likely diagnosis: DM Type 1 DM Type 2 MODY 1 MODY 2 LADA

7. ?Pathogenesis: Whitish vaginal discharge. Proteinuria Bacterial infection Glycosuria Trichomoniasis Candidiasis

8. “Nothing great in the world has ever been accomplished without passion” - - CHRISTIAN FRIEDRICH HEBBEL

9. Most likely .. What type of DM ? 56 year male obese 30 year female following pregnancy 8 year old boy, poor growth, DKA. 24 year female Cushing’s sy 68 Year male following Ca. pancreas. 32 male, DM, BMI 18, Anti-GAD +ve. 34 year male, extensive tuberculosis. 12 year old female following viral fever 41y DM2, BMI 17.1, HbA1c 14.1, DKA 15y male, BMI 16.2, recurrent infect. II NIDDM II GDM I IDDM Sec IDDM Sec IDDM I LADA Sec IDDM I IDDM LADA MODY

10. The foundation of lasting self-confidence and self esteem is excellence, mastery of your work.- Brian Tracy

11. Pathology of Diabetes Dr. Venkatesh M. Shashidhar Assoc. Prof. & Head of Pathology

13. 1788 – Cawley – damaged pancreas in DM.

15. World Statistics:

16. Diabetes Mellitus - Definition 2nd Century, Greek physician, Aretus named Diabetes from diabainein, “to flow through or siphon & Mellitus meaning sweet/Honey. * insipidus  tasteless – dilute urine. Disorder of metabolism (Carb, Prot & Fat) Absolute/Relative deficiency of insulin. Characterized by hyperglycemia. Polyuria, Polydypsia, Polyphagia.

17. Criteria for the Diagnosis of Diabetes A random blood glucose concentration of 11mmol/L or higher, with classical signs and symptoms. or A fasting glucose concentration of 7mmol/L or higher on more than one occasion. or An abnormal oral glucose tolerance test (OGTT, done for borderline 5.5-6.9 mmol/L ), in which the glucose concentration is >11mmol/L at 2 hours after a standard carbohydrate load (75 gm of glucose).

18. Pancreas Normal Anatomy:

19. Normal Pancreas:

20. Normal Pancreas: Duct Islet of Langerhans (Endocrine Pancreas) Pancreatic acini (Exocrine Pancreas)

21. Normal Pancreatic Islet: (ipx stain) ß α αcells 20%(Glucagon) ß cells 70%(Insulin) Other Cells in Islets: δ cells - Somatostatin PP Cells - pancreatic polypeptide D1 cells – Vasoactive Intestinal Polypeptide Enterochromaffin – Seratonin.

22. Blood Glucose & Hormones Hormones Insulin Glucortocoids Glucagon Growth Hormone Epinephrine Action  Glucose  Glucose  Glucose  Glucose  Glucose Maintained within 3.5-5.5mmol/l.

23. Insulin secretion:

24. Insulin - Anabolic Steroid Transmembrane transport of glucose (Liver, muscle & adipose tissue. Maintain metabolism: Striated Muscle glucose uptake Adipose tissue lipogenesis Hepatic gluconeogenesis.  glycogen & gluco-neogenesis.  lipolysis  Lipogenesis.  Protein & triglyceride synthesis  Nucleic acid & Protein synthesis In DM  Insulin   glucose &  catabolism

25. InsulinAnabolic SteroidGLUT4* only these tissue….!

26. DM2: Pathogenesis – 3 mechanism. Non-Insulin Requiring Cells Blood Vessels Nerves & Brain Kidney, Eye Lens Intracellular Hyperglycemia Glucose polymers “Polyol” damage Excess glucose: Glucose  Aldosereductase Sorbitol (Polyol)  Osmotic cell swelling and dysfunction. Insulin Requiring Cells Striated Muscle Liver Adipose Tissue Intra cellular hypoglycemia Low glucose: Liver: Gluconeogenesis Adipose: Lipolysis  FFA Extracellular hyperglycemia Vascular & tissue damage…*

27. DM2: Pathogenesis Liver & skeletal muscle insulin resistance β-cell hypersecretion β-cell failure Lipotoxicity decreased incretin secretion increased glucagon secretion increased renal glucose re-absorption appetite dysregulation

28. New in DM Pathogenesis: Incretins. Insulin release through Incretins (from intestine) in response to glucose intake. Glucagon-like Peptide-1 (GLP-1) Glucose-dependent InsulinotropicPolypeptide (GIP) stimulate βcells (Insulin) & Inhibit α (glucagon) Destroyed by dipeptidyl peptidase (DPP). Dysregulation in DM2 (early breakdown). Two new drugs, exenatide (GLP-1 mimetic) and sitagliptin [DPP 4 inhibitor] – Approved for PBS. http://www.medscape.com/infosite/dia/article-3 http://video.medscape.com/pi/editorial/cmecircle/2004/3418/flash/beaser/index.html

29. Incretins: physiology

30. Diabetes Classification: (not a single disease) Primary DM Type I – IDDM / Juvenile – 5-10%. Type II – NIDDM /Adult onset – 90-95%. MODY – 5% Maturity Onset Diabetes of Youth Genetic, sub types MODY 1–6, LADA – Latent Autoimmune Diabetes in Adults (LADA) Gestational Diabetes Mellitus. Other. Secondary DM Excess hyperglycemic stimulus. Cushings, Phaeochromocytoma, acromegaly, Steroid therapy. Beta cell destruction: Pancreatitis/tumors/Hemochromatosis Infectious – congenital rubella, CMV, TB, Endocrinopathy, Downs Sy.

31. Metabolic Syndrome (X) - IDF criteria Central Obesity >90cm male, >80 fem – Asian, chinese, Jap. >94cm male, >80 fem – Europ, Africa, Arab. + Any two of the following. Raised triglycerides >1.7mmol/l or treat. Reduled HDL-C <1.03mmol/l or treat. Hypertension 130/85 or treat. Fasting plasma glucose >5.6mmol/l or DM2. Australia prevalence 2005 – 30.7% 10 Year CVD risk - 23.4%

32. LADA: Late onset Autoimmune DM Features of both type 1 and type 2. Younger, Rapid onset & progression to insulin dependency. Immune markers like type 1 diabetes, may lack ketoacidosis symptoms. Incidence: - 6-10% (UK). Diagnosis: Elevated pancreatic autoantibodies Risk factors: Metabolic Syndrome LADA + Metabolic syndrome = DM Type 1.5. Complications of both type 1 & 2. (metabolic, Macro & Microangiopathy etc).

33. MODY: Maturity Onset Diabetes of Young. 5% of DM, Young*, non obese, insulin release defect* Like DM2, non-ketotichyperglycemia, no DM Antibodies. Auto. Dom. - Monogenic – Genetic testing*. Treatment is specific to type. Unline type 1 or 2 Also known as Type 1.5 (MODY + LADA) Subtypes: 1,2,3,4,5,6 – type 3 & 2 common. 1,3,4,5,6 – Insulin transcription defect  HNF. Type 2 – Enzyme glucokinase, defective β cell response.

34. One machine can do the work of fifty ordinary men. No machine can do the work of one extraordinary man.- - Elbert Hubbard

36. Graves, Hashimoto thyroiditis.

37. Rheumatic heart disease

38. SLE, Collagen vascular disease

39. Rheumatoid arthritis.Insulin deficiency ß cell Destruction Antibodies: Islet cell Ab - ICA Insulin Auto Ab - IAA Glut. Acid Decarb - GAD65 Autoimmune Insulitis Ab to ß cells/insulin Secondary DM Inflammation, Tumor, Infection Trauma Pancreatitis Environment Viral infe..? Genetic HLA-DR3/4

40. Insulitis – Type I Lymphocytes.

41. DM1Course:

42. Progression of Type II Years ..

43. Relative Insulin Def. Pathogenesis of Type II DM ß cell Exhaustion (IDDM)

44. Insulin Resistance: Diabetes

45. Insulin Resistance:JCU Research…!

46. DM2 Islets:Normal early  amyloid late:  Normal. Loss of ß cells (only in late stage) replaced by Amyloid protein deposit (hyalinization).

47. Type-I Type-II Less common (10%) Children < 25 Years Insulin- Dependent Duration: Weeks Acute Metabolic complications Autoantibody: Yes Family History: No Insulin levels: low Islets: Insulitis 50% in twins More common (90%) Adult >25 Years NIDDM* Months to years Chronic Vascular complications. No Yes Normal or high * Normal / Exhaustion ~100% in twins

48. Type-I Type-II Insulitis: Lymphocytic infiltrate within islets. Islet Hyalinization: Central hyaline deposits replacing dead beta cells (only in late stage…!)

49. Being a good human is maintaining complete harmony between thought, word and deed. Divergence between thought, word and deed is the cause of all our problems…!- BABA.

50. DM Complications: Glucose is highly reactive - damages tissues. Glucose absorption, storage & use – Timely Insulin release - critical. Diabetes is state of insulin deficiency. Absolute/Delayed/inappropriate insulin response Glucose excess – Hyperglycemia. Neo-glucogenesis – Proteolysis, lipolysis Clinical symptoms & signs are mainly due to complications. Complications: Acute Metabolic & Chronic Vascular. Damage to BV, Kidney, CNS & immune system.

51. Diabetes Complications: Short term Complications: (metabolic) Hypoglycemia Diabetic Ketoacidosis Non Ketotic hyperosmolar diabetic coma Lactic acidosis Long term Complications: (Angiopathy) Microngiopathy - Retinopathy, Nephropathy, Neurophathy, dermatopathy. Macroangiopathy – Atherosclerosis.

52. Pathogenesis of complications: Insulin dependant tissue: Striated muscle, adipose tissue & Liver. Low glucose inside cell decreased cell metabolism. High glucose outside Glycosylation damage (AGE), cross linking, trap plasma proteins, LDL, cholesterol, - * Insulin independent tissue: BV, nerve, (kidney, eye, CNS) Excess glucose  Sorbitol, Polyol osmotic damage* Excess glucose  Diacylglycerol (DAG)Activation of Protein Kinase C  angiogenesis, BM matrix.

54. DM:Complications:

55. The best gift of Nature to man is the briefness of his life…!Latin quote

57. Glycosylation of basement membrane proteins  Leaky blood vessels.

58. Deposition of proteins, matrix, LDL.

59. Narrow, thick, fragile, Leaky BV.

60. Ischemia, defective inflammation.

61. Leakage – edema, Proteinuria (kidney)

62. Micro Aneurysms (retina)

64. Glycosylation

65. BM damage leak

66. ‘AGE’ depositionDiabetic

67. Neuropathy Sensory  Motor (myelin) Peripheral Neuropathy Bilateral, symmetric Progressive, irreversible Paraesthesia, pain, muscle atrophy Visceral neuropathy Cranial nerve – diplopia, Bells palsy GIT- constipation, diarrhoea CVS – orthostatic hypotension

68. DM-Neuropathy – Myelin stain Myelin loss in nerve Normal

70. Nephropathy Nodular Glomerulo Sclerosis. Common morbidity & mortality. Deposition of ‘AGE’ Advanced Glycosylation End-products as nodules. Nephrotic syndrome Pyelonephritis End stage renal failure

71. Diabetic Nephropathy Microangiopathy, atherosclerosis & infections: Diffuse or nodular diabetic glomerulosclerosis (Kimmelstiel Wilson Sy) Renal arteriolosclerosis & atherosclerosis Necrotizing renal papillitis. Pyelonephritis. End stage kidney.

72. Nodular Glomerulosclerosis – KW

73. Diabetic Glomerulosclerosis A B A: Nodular glomerulosclerosis. B: Hyaline Arteriolosclerosis.  What is the pathogenesis?

74. DM Kidney: advanced (KW Lesion) A B

75. DM Kidney: thickening of BM (PCT) DCT PCT PCT: Proximal Convoluted Tubule, DCT: Distal Convoluted Tubule

76. Gross : Diabetic kidney

77. Nephropathy – Progression:

78. Nephropathy Classes: I - IV

79. DM with Infarction: Papillary necrosis

80. Retinopathy: Non Proliferative Microaneurysms, Dots & blots Hard and soft exudates Cotton wool – infarcts Macular edema. Proliferative. Neovascularization Large hemorrhages Retinal detachment.

81. Non Proliferative Retinopathy Venous dilation and small red dots posterior retinal pole - capillary micro-aneurysms. Dot and blot retinal hemorrhages and deep-lying edema and lipid exudates impair macular function. Cotton-wool spots (soft exudates) - microinfarcts due to ischemia. They are white and obscure underlying vessels. Hardexudates are caused by chronic edema. They are yellow and generally deep to retinal vessels. Late generalized diminution of vision due to ischemia and macular edema - common cause of visual defect (best detected by fluorescein angiography)

82. Proliferative Retinopathy Neovascularization – new capillaries grow into the vitreous cavity. hemorrhages may lead to sudden severe loss of vision. In advanced disease, neovascular membranes can occur, resulting in a traction & retinal detachment. Leading to permanent blindness. Panretinal photocoagulation may diminish or eliminate proliferative retinopathy

83. Normal Retina

84. Diabetic Retinopathy

85. Diabetic Retinopathy Fluorescein angiogram of the eye of a diabetic patient. Note the numerous, small, dot-like capillary microaneurysms.

86. Diabetic Retinopathy Pre retinal Hemorrhage - detachment

87. You must learn to distinguish between good and bad, truth and untruth. You must use your education for the purpose of serving community. - Sai - Summer Showers, 1973.

88. Macroangiopathy Atherosclerosis Dyslipidemia  HDL Non-Enzymatic Glycosylation  Platelet Adhesiveness  Thromboxane A2  Prostacyclin Endothelial damage  Atherosclerosis MI, CVA, Gangrene of Leg (PVD), Renal Insufficiency

89. Atherosclerosis:

90. Fungal infections: Candidiasis

91. Macrosomia With Polycythemia

92. Blood vessel calcification: In digital arteries in DM Amputated Toe Calcified BV

93. Cataract – Sorbitol.. Polyol..osmotic.. Lens epithelium (Insulin independent) is exposed to Hyperglycaemia, excessive flux of glucose to sorbitol by the polyol pathway. The accumulation of intracellular sorbitol exerts osmoprotection and prevents cell shrinkage. The excessive accumulation of sorbitol, causes an increased osmotic load within the lens causing swelling, fibre breakdown, and opacification (the osmotic hypothesis). Other mechanisms, including glycation and oxidative stress, may also be responsible for lens opacification.

95. Pathogenesis of Infections in DM: Multifactorial: Impaired inflammation – BV thickening – Decreased immune function: WBC, chemical mediator glycosylation. Glycosylation of immune mediators. Abs. Tissue damage: Ischemia & infarctions. Decreased metabolism – low immunity. Increased glucose (alone is not the cause*)

96. Laboratory Diagnosis: Urine glucose - dip-stick –Screening Fasting > 7mmol, Random >11mmol If Fasting level is 5.5 to 7  OGTT HbA1c - for follow-up, not for diagnosis Fructosamine – similar to HbA1c - long term maintenance. Antibodies – Type-1 Gene testing: MODY

97. “It's not that I'm so smart, it's just that I stay with problems longer”…! --Albert Einstein

98. CPC-3.2– END–DM2 Pathology – Major Core Learning Issues: Pathology of Diabetes Overview & Classification. Pathological basis of clinical features. Details of Type 1 & 2 (Etiology, pathogenesis, morphology, clinical features) Complications of Diabetes: Micro & Macroangiopathy. Retinopathy, nephropathy, neuropathy, dermatopathy.. etc.. & Metabolic complications (ketoacidosis, coma etc) Laboratory diagnosis of diabetes. (GTT, HBA1c, etc) Pathology – Minor CLI: Metabolic Syndrome (Syndrome X). MODY, LADA, Gestational, childhood type 2, Secondary diabetes, Bronze diabetes. Hyperglycemia Syndromes: Cushings, drugs, etc. Hypoglycemia syndromes, Insulinoma. New research & developments

99. Case 1 A 29y woman BMI = 33 kg/m2. complains of declining visual acuity since 6 months. Fundoscopic examination shows peripheral retinal microaneurysms. Urinalysis reveals 3+ proteinuria and 3+ glucosuria. Serum albumin is low & cholesterol is high. These clinicopathologic findings are best explained by which of the following pathologic mechanisms of disease

100. Pathologic mechanism? Anti-insulin antibodies. Increased insulin uptake. Irregular insulin secretion. Peripheral insulin resistance. Serum Anti GAD-67 antibodies.

101. DM– Pancreatic Islet- ? Feature shown by arrow? Β cell exhaution. Amyloid deposits Lymphocytic Insulitis Pancreatic acinus Chronic Pancreatitis

102. 50y, male DM2, kidney biopsy. Likely nature of feature shown by arrow? Amyloid protein. AGE protein Basement mem protein. Fibrinoid necrosis. Inflammatory cells.

103. 47y F, DM2 - foot ulcer: ? Diagnosis Fungal infection Neuropathic ulcer Venous ulcer Arterial ulcer Atypical TB in AIDS

104. Thickening of small BV in this patient is most likely related which pathologic mechansim? Glycosylation of hemoglobin. Inadequate inflammtion resp. Insulin resistance in tissues. Increased Atherosclersis. Microvascular disease.

105. 57y M, DM2: Gross Kidney- arrow ? feature Benign nephrosclerosis. Glomerulonephritis Papillary necrosis Nodular glomerulosclerosis Renal artery Atherosclerosis

106. DM– Pancreatic Islet- ? Feature shown by arrow? Β cell exhaution. Amyloid deposits Lymphocytic Insulitis Pancreatic acinus Chronic Pancreatitis

107. 47y F, DM2 – Kidney- arrow ? feature Nodular glomerulosclerosis. Artereolosclerosis Atherosclerosis AGE deposition Diffuse glomerulosclerosis

108. DM Kidney.Microscopy. ? Feature Arrow B Nodular sclerosis Artereolosclerosis Diffuse sclerosis Pyelonephritis Abscess formation A B

109. DM Kidney.Microscopy. ? Feature Arrow A Nodular sclerosis Artereolosclerosis Diffuse sclerosis Pyelonephritis Abscess formation A B

110. 57y M, DM2 – Kidney- arrow ? feature Dot hemorrhage Hard exudate Soft cotton wool exudate Neovascularization Micro Aneurysm

111. 57y M, DM2 – Eye ? Pathogenesis AGE deposition Glycosylation Collagen deposition Osmotic Polyol damage Artereolosclerosis

112. 47y F, DM2 - foot ulcer: ? Diagnosis Fungal infection Neuropathic ulcer Venous ulcer Arterial ulcer Atypical TB in AIDS

113. 56y Fem, Anterior wall MI. 3+ proteinuria & FBG 19mmol/L. Image shows her pancreas. What complication she may develop? Gall stones. Chronic pancreatitis. Uric acid stones. Gangrene of foot. Pancreatic carcinoma

114. A 65y man, BMI 40, peripheral neuropathy, retinopathy and abdominal aortic aneurysm is now developing renal failure. His FBS is 18.3 mmol/L, microscopic examination of his renal biopsy. What is the microscopic feature shown? Renal papillary necrosis. Nodular glomerulosclerosis. Hyaline artereolosclerosis. Atrophy + Amyloid deposition. Diffuse glomerular sclerosis. What is the chemical nature of nodular deposit within glomerulus? Briefly describe steps in the Pathogenesis of nodular glomerulosclerosis? What other renal pathology are commonly seen in diabetic patients?

115. A 47 year old man, Hypertensive & DM2 since 6 years for checkup. Complains of his vision as spectacles recently made does not seem to help. Image shows his fundoscopy. What is the most likely diagnosis ? Normal fundus. Mild Hypertensive retinopathy. Non proliferative retinopathy. Proliferative retinopathy. Retinal detachment. Retinopathy – Differences between Hypertensive & Diabetic retinopathy? Briefly describe steps in the Pathogenesis of diabetic retinopathy? Differentiate soft & hard exudates, dots & blots, proliferative & non-proliferative.?

116. A 65y man, BMI 40, Diabetes since 18 years. His FBS is 18.3 mmol/L, is now developing hypertension since 3 years (BP 186/98 mm of Hg) . Image shows microscopic appearance of his renal biopsy. What microscopic feature shows pathogenesis of high blood pressure? Hyperplasticartereosclerosis Protein cast within tubule. Artereolosclerosis. Nodular glomerulosclerosis. Both A & C. What is the pathogenesis of feature A (hyperplasticarterosclerosis) in the image? Briefly describe feature B and its clinical presentation? What is seen in the interstitium of this kidney? Pathogenesis? Clinical feature?

117. A 42 year female presents with recent onset polyuria, polydypsia and decreasing vision. HbA1c was 16.1%. She is chronic alcoholic with past history of jaundice. Image shows her pancreatic biopsy compared with normal. What is the most likely diagnosis ? Secondary diabetes. Late onset Type 2 diabetes. Chronic cholecystitis. Cushing’s syndrome. Type 1 diabetes. Normal Patient Briefly describe features of LADA? What further investigations can be done to confirm the diagnosis? List & briefly describe other types of Diabetes ?

118. 70y man brought from nursing home with progressive confused & disoriented status since 2 weeks. Not eating or drinking well. On steroid therapy for COPD. What is the most likely diagnosis ? Diabetic ketoacidosis. Non-ketotichyperosmolar coma. Diabetic lactic acidosis. Respiratory acidosis. Diabetic nephropathy. Lab tests: List & briefly discuss common metabolic complications of Diabetes? ? ?

119. The most splendid achievement of all is the constant striving to surpass yourself and to be worthy of your own approval.- - Denis Waitley

121. Optic disc

122. Macula

123. Blot hem

124. Cotton wool / soft dep.1. 2. 3. 4. 5.

125. Label the diagram. 1. 2. 3. 4. Capillary Nodule – AGE Bowman cap. Hyaline arteriolo sclerosis in arteriole.

126. Diabetic Retinopathy Dot hem Blot hem Neovascul. Cotton wool Cotton wool

127. Neuropathic Arthropathy: Charcot’s foot. Acute, swollen, red, warm Minimal or no pain. No or minimal h/o trauma. Pathogenesis: Neuropathyosteoporosis# Chronic - Foot deformity. Normal Charcot

128. DM Amyotrophy- Painful muscle wasting Pain & weakness of lower limb muscles. Neuropathy. Muscle wasting. Minimal sensory loss. Loss of knee reflex. Inflammation in spinal cord.

129. Chronic Polyneuropathy Claw foot – Dermopathy & Neuropathy Pathophysiology: (unknown) Polyol  Sorbitol  damage. Ishcemic injuty. Impaired Nerve growth factor. Autoimmune damage.

131. Poor diabetic control – hyperglycemia – AGE.

132. Occlusion of capillaries of proximal lumbar plexus  nerve damage. (no myelin degeneration*)

134. Case 2 – 58y Fem Asymptomatic. She has a BMI of 29 and is on enalapril for hypertension. She has no symptoms of diabetes. A fasting glucose is 6.5mmol/L. Mother had DM type2. Should she be tested for DM? Indications? Yes. (IGTT, IFG, Aboriginals, High risk immig, Obese fem+, cardiac event, >45y+ BMI>30, FH of DM2 or HPTN). Diagnosis? next investigation for this patient? IFG, oGTT (FG 5.5-7, RG 7-11 mmol/L) How do you manage a IGT patient? Advice about Diet & excercise.

135. CPC-3.2– KFP Questions: DM – Definition, epidemiology Type I,II, NIDDM, IDDM, GDM, MODY. Etiology, Risk factors Pathogenesis of Clinical features – PPP Complications Acute – metabolic – ketoacidosis, coma Chronic – vascular – Micro/Macro Glycosylation, AGE, Polyols Lab Diagnosis – FBS, GTT, KFT, Lipids.

136. Summary Abnormal metabolic state characterised by glucose intolerance due to inadequate insulin action. Type I (juvenile onset) Autoimmune destruction of β-cells (Genetic + ? Virus + Autoimmunity); insulin-dependent – Treat by Insulin. Type II (maturity onset) - defective insulin action – peripheral resistance to insulin. treatment by life style change & oral hypoglycaemic agents. Complications: accelerated atherosclerosis, susceptibility to infections, and microangiopathy (retinopathy, neuropathy, dermatopathy, nephrophathy)

137. Points to remember/review: Diabetes is a state of hyper ketabolism. Increased fat & protein breakdown, wt loss. Blood vessel damage – arteriosclerosis is central to chronic complications. Increased Infections – why?. Glucose control is critical * why? Hypoglycemia is more dangerous. Not hyper FBS, GTT & HbA1C – interpretation.

138. Questions.. How – Ketoacidosis? How – hypoglycemia ? Macro Angiopathy ? – (atherosclerosis) Micro Angiopathy “Pathy” (arteriolosclerosis) Retinopathy – types, morphology, Nephropathy – types, morphology. Dermatopathy – morphology. Diabetic Amyotrophy - What is Diabetes insipidus ?

139. 56y woman, nocturia 56y Fem, 3/12 nocturia excessive thirst and polyuria(1-4 times) disturbing her sleep. Recently noticed blurring of vision, & tingling sensation in her toes on both sides. Weight 94kg & height 1.71m. BMI 32. Hypertensive for several years. Mother diabetic type2. Glucometer capillary BS is 15mmol/L. What further Investigations? Ans: Twice..Lab RBS/FBS, GTT. Why not HbA1c for diagnosis? 60% of new diabetics have normal HbA1c. What other investigations should be done? Retina, urine, Lipid profile, Cardiac exam.

140. It is a matter of great satisfaction if you are educated on the right lines, become an example to others and accept positions of responsibility. In all these things, always keep “Truth & Love for all” as your goal.Then only you will get the Grace of God….!- Sai - Summer Showers, 1973.

141. Site of action of Anti DM drugs:

142. Metabolic (short term) complications:

143. Diagnostic criteria for DM, IFG, and IGT

144. DECODE: increased 2-hour glucose is associated with increased mortality rate (adjusted for age, center, and gender).

145. Cumulative incidence of diabetes mellitus (based on American Diabetes Association criteria) according to study group in the DPP. * The incidence of diabetes differed significantly among the 3 groups (p <0.001 for each comparison. Reprinted with permission from Knowler et al.13

146. Endocrinology Other : (Brief notes) Tumours – adenomas of endocrine gl. Cushings disease. Pheochromocytoma. Zollinger Ellison syndrome. MEN Syndromes – MEN type 1 & 2.

147. Diabetic Retinopathy Neovascularization Cotton wool spots

148. Diabetic Retinopathy Advanced fibrous plaques

149. Diabetic Retinopathy - Proliferative

150. Diabetic Retinopathy - Proliferative

151. Normal Retina:

152. Progression of Type I

154. DM - Clinical Examination:

155. Daily changes in hormone…