Ueda 2016 2-pathophysiology ,classification & diagnosis of diabetes - khaled el hadidy
- 1. Pathophysiology, Screening, Diagnosis & Classification Of Diabetes UEDA Diabetes Mini-Course Aswan Feb. 2016 DR. Khaled El Sayed El Hadidy. MD Professor of Internal Medicine Head of Internal Medicine Department Head of Diabetes and Endocrinology Unit Beni - Suef University. UEDA ( IDF member )
- 2. Classification, Pathophysiology & Diagnosis of Diabetes “1” Agenda 1.Normal physiology. 2.Definition & C/P. 3.Clinical classes of Diabetes Mellitus.
- 3. Classification, Pathophysiology & Diagnosis of Diabetes “1” Agenda 1.Normal physiology. 2.Definition & C/P. 3.Clinical classes of Diabetes Mellitus.
- 7. Classification, Pathophysiology & Diagnosis of Diabetes “1” Agenda 1.Normal physiology. 2.Definition & C/P. 3.Clinical classes of Diabetes Mellitus.
- 8. Definition of diabetes Chronic hyperglycemia associated with long term damage to …. Eyes Kidneys Nerves Heart and blood vessels Gums •
- 9. Signs and symptoms of hyperglycaemia Polydipsia Polyuria Nocturia Visual disturbance Fatigue Weight loss Infections Hunger
- 10. Classification, Pathophysiology & Diagnosis of Diabetes “1” Agenda 1.Normal physiology. 2.Definition & C/P. 3.Clinical classes of Diabetes Mellitus.
- 11. Clinical classes of diabetes: 1. Type 1 diabetes – results from B cell destruction due to an autoimmune process usually leading to insulin deficiency. 2. Type 2 diabetes – results from a progressive insulin secretory defect on the background of insulin resistance. 3. Gestational diabetes mellitus (GDM) – any degree of glucose intolerance with onset or first recognition during pregnancy. 4. Other specific types of diabetes – due to other causes such as genetic defects in Beta cell function, genetic defects in insulin action, diseases of the exocrine pancreas (e.g. cystic fibrosis), and drug- or chemical-induced causes (e.g. in the treatment of HIV/AIDS or after organ transplantation).
- 12. Type 2 Diabetes UEDA Diabetes Mini-Course Aswan Feb. 2016
- 13. Pancreatic islet dysfunction (T2DM) ↑ Glucose Fewer -cells -cells Hypertrophy Insufficient Insulin Excessive Glucagon –+ ↓ Glucose Uptake ↑ HGO + HGO=hepatic glucose output. Adapted from Ohneda A, et al. J Clin Endocrinol Metab. 1978; 46: 504–510; Gomis R, et al. Diabetes Res Clin Pract. 1989; 6: 191–198.
- 14. Pathogenesis of Type 2 Diabetes Hyperglycemia Liver Increased Glucose Production Reprinted with permission from DeFronzo RA. Diabetes. 1988;37:667-687. Copyright © 1998 American Diabetes Association. All rights reserved. Impaired Insulin Secretion Pancreas Liver Decreased Glucose Uptake Muscle
- 15. Pathophysiology of Type2 Diabetes
- 17. Muller WA, et al. N Engl J Med. 1970;283:109-115. 80 100 120 140 160 –60 0 60 120 180 240 Time (min) Glucagon(pg/mL) 0 50 100 150 –60 0 60 120 180 240 Insulin(μU/mL) NGT T2DM Insulin Glucagon Islet dysfunction: Inappropriate Insulin and Glucagon Responses to Glucose in Patients With T2DM NGT T2DM
- 18. Natural History f Type 2 Diabetes
- 19. Pathophysiology of Type2 Diabetes
- 20. Incretins Intestine Secretion Insulin = Incretin Incretins are insulinotropic substances released by the GIT. Incretins account for approximately 20%–60% of insulin secretion after a meal in normal individuals. ~90% incretin activity is due to: Glucagon-Like Peptide-1 (GLP-1) Glucose-dependent insulinotropic polypeptide (GIP).
- 21. L L L GLP-1 GLP-1 GLP-1 InsulinGlucagon Slowed gastric emptying Early Satiety Inactive GLP-1 DPP-4 enzyme GLP-1
- 22. Incretin Effect in Subjects without and with Type 2 Diabetes Given Glucose by IV and Orally Time, min IRInsulin,mU/L nmol/L 0.6 0.5 0.4 0.3 0.2 0.1 0 80 60 40 20 0 18060 1200 Control Subjects (n=8) Patients with Type 2 Diabetes (n=14) Time, min IRInsulin,mU/L nmol/L 0.6 0.5 0.4 0.3 0.2 0.1 0 80 60 40 20 0 18060 1200 Oral glucose load Intravenous (IV) glucose infusion Incretin Effect Nauck M et al., Diabetologia 1986; 29:46–52
- 23. Increased HGP Increased Glucagon secretion Decreased insulin secretion Decreased glucose uptake HYPERGLYCEMIA Neurotransmitter dysfunction Islet α-cell Decreased incretin effect Increased lipolysis Increased glucose reabsorption A New Paradigm for the Pathophysiology and Treatment of Type 2 Diabetes Mellitus Ominous Octet De Fronzo RA. Diabetes 2009;58:773–95 HGP = hepatic glucose production
- 24. SCREENING & DIAGNOSIS SD1 Each health service should decide whether to have a program to detect people with undiagnosed diabetes. Universal screening for undiagnosed diabetes is not recommended. SD2 Detection programs are usually based on a two-step approach: Step 1 Identify high-risk individuals using a risk assessment questionnaire. Step 2 Glycemic measure in high-risk individuals.
- 25. Individuals Considered To Be At High Risk Of Type 2 Diabetes People with IGT or IFG All patients with a history of a cardiovascular event (acute myocardial infarction, angina, peripheral vascular disease or stroke) People aged 35y and over originating from the Pacific Islands, Indian subcontinent or China People aged 40y and over with body mass index (BMI) ≥30 kg/m2 or hypertension Women with a history of GDM Women with polycystic ovary syndrome (PCOS) who are obese Patients on antipsychotic medication
- 26. Non-modifiable Risk Factors For Type 2 Diabetes Age > 40 years Family history or genetic predisposition Ethnicity History of IGT, IFG Vascular disease History of gestational diabetes or delivery of macrosomic baby PCO Schizophrenia Hypertension Dyslipidaemia
- 27. Modifiable Risk Factors For Type 2 Diabetes Abdominal or central obesity Overweight Physical inactivity Dietary factors
- 28. FPG 100–125 mg/dL (5.6–6.9 mmol/L): IFG OR 2-h plasma glucose 140–199 mg/dL (7.8– 11.0 mmol/L): IGT OR A1C 5.7–6.4% Prediabetes* * For all three tests, risk is continuous, extending below the lower limit of a range and becoming disproportionately greater at higher ends of the range. American Diabetes Association Standards of Medical Care in Diabetes. Classification and diagnosis of diabetes. Diabetes Care 2016; 39 (Suppl. 1): S13-S22
- 30. SD4 Where a random plasma glucose level ≥ 100 mg/dl and < 200 mg/dl is detected, a FPG should be measured or an HbA1c measured. SD5 Use of HbA1c as a diagnostic test for diabetes requires that stringent quality assurance tests are in place and assays are standardized to criteria aligned to the international reference values, and there are no conditions present which preclude its accurate measurement. SD6 People with screen-detected diabetes should be offered treatment and care. SCREENING & DIAGNOSIS
- 31. Impaired glucose tolerance Impaired fasting glucose Intermediate states High risk of developing diabetes Increased risk of cardiovascular disease Prevention strategies must be implemented to prevent or delay progression
- 32. Metabolic syndrome Cluster of risk factors or syndrome Found in 70 - 80% of people with T2DM Diagnostic criteria varies globally Associated with three-fold increase in heart disease and stroke Associated with two-fold increase in major cardiovascular events (International Diabetes Federation, 2006)
- 33. Revised ATP III Metabolic Syndrome Oct 2005 *Diagnosis is established when 3 of these risk factors are present. †Abdominal obesity is more highly correlated with metabolic risk factors than is BMI. ‡Some men develop metabolic risk factors when circumference is only marginally increased. <40 mg/dL <50 mg/dL or Rx for ↓ HDL Men Women >102 cm (>40 in) >88 cm (>35 in) Men Women 100 mg/dL or Rx for ↑ glucoseFasting glucose 130/85 mm Hg or on HTN Rx Blood pressure HDL-C 150 mg/dL or Rx for ↑ TGTG Abdominal obesity† (Waist circumference‡) Defining LevelRisk Factor
- 34. Type1 Diabetes UEDA Diabetes Mini-Course Aswan Feb. 2016
- 35. Pathogenesis of type 1 diabetes Immunological activation Progressive beta-cell destruction Insufficient beta-cell function Genetic susceptibility Immune factors Other autoimmune disease Antigen-specific antibodies Environmental trigger Viruses Bovine serum albumin Nitrosamines: cured meats Chemicals: vacor (rat poison), streptozotin
- 36. Pathogenesis of type 1 diabetes
- 37. Gestational Diabetes UEDA Diabetes Mini-Course Aswan Feb. 2016
- 38. Gestational Diabetes Care In Upper Egypt
- 39. Gestational Diabetes One of the most challenging aspects of diabetes practice Seemingly easy: Practically difficult Needs a lot of commitment on part of doctor, patient and family Success can be achieved if we try together
- 40. Definition Glucose intolerance with onset or first recognition during pregnancy Characterized by β-cell function that is unable to meet the body’s insulin needs Buchanan, Wiang, Kjos, Watanabe 2007
- 41. Pathophysiology of GDM Insulin Resistance Relative Insulin Deficiency
- 42. Risk factors for GDM High risk Obesity Age >25ys Diabetes in 1st degree relative Previous history of GDM or glucose intolerance Previous infant with macrosomia > 3.5 kg High risk ethnic group; South Asian, East Asian, Indigenous American or Australian, Hispanic PCOS Low risk Age less than 25 years No previous poor pregnancy outcomes No diabetes in 1st degree relatives Normal prepregnancy weight and weight gain during pregnancy No history of abnormal glucose tolerance Perkins, Dunn, Jagastia, 2007
- 44. Why diagnose and treat GDM? No increase in congenital anomalies Short term risks for the baby Macrosomia Neonatal hypoglycemia Jaundice Preterm birth Birth injury Hypocalcemia/ hypomagnesimia Respiratory distress syndrome Long term risks for the baby Obesity Type 2 diabetes
- 45. GDM Diagnosis 2 Approaches for Diagnosing Gestational Diabetes Mellitus (GDM) AACE- and ADA- recommended 1-step 75-g 2-hour oral glucose tolerance test (OGTT) 1,2 or ACOG- recommended 2 steps: a 50-g 1-hour glucose challenge test (GCT) ≥140 mg/dL , followed by a 100-g 3-hour OGTT (if necessary)3 GDM Diagnostic Criteria for OGTT Testing 75-g 2-hour† 100-g 3-hour* Fasting plasma glucose (FPG) ≥92 mg/dL (5.1 mmol/L)2 ≥95 mg/dL (5.3 mmol/L)2 1-hour post-challenge glucose ≥180 mg/dL (10.0 mmol/L)2 ≥180 mg/dL (10.0 mmol/L)2 2-hour post-challenge glucose ≥153 mg/dL (8.5 mmol/L2 ≥155 mg/dL (8.6 mmol/L)2 3-hour post-challenge glucose ≥140 mg/dL (7.8 mmol/L)2 †A positive diagnosis requires that test results satisfy any one of these criteria *A positive diagnosis requires that ≥2 thresholds are met or exceeded .1AACE. Endocr Pract. 2011;17(2):1-53. .2ADA. Diabetes Care. 2013;36(suppl 1):11-66. .3Committee on Obstetric Practice. ACOG. 2011;504:1-3.
- 46. Recommendations: Detection and Diagnosis of GDM (1) Screen for undiagnosed type 2 diabetes at the first prenatal visit in those with risk factors, using standard diagnostic criteria Screen for GDM at 24–28 weeks of gestation in pregnant women not previously known to have diabetes Screen women with GDM for persistent diabetes at 6–12 weeks postpartum, using OGTT, nonpregnancy diagnostic criteria ADA. III. Detection and Diagnosis of GDM. Diabetes Care 2014;37(suppl 1):S18
- 47. Lastly we hope that course will achieve its goals and help you all in getting the best of the forthcoming conference UEDA Board UEDA Diabetes Mini-Course Aswan Feb. 2016