1. סכרת נעורים 2012 איבחון וקלסיפיקציה של סכרת נעורים קטואצידוזיס: הגדרה וטיפול

2. סכרת נעורים : 2005 אבחון וקלסיפיקציה של סכרת נעורים Expert Committee on the Diagnosis and classification of Diabetes Mellitus Diabetes care, July 1997 National Diabetes Data Group (NDDG) - 1979 WHO - 1980-1985.

3. סימפטומים של סכרת נעורים פוליאוריה פולידיפסיה אבדן משקל פוליפאגיה (לעתים) טשטוש ראיה (לפעמים)

4. Etiologic classification of diabetes Type 1 diabetes Type 2 diabetes - may range from predominantly insulin resistance with relative insulin deficiency to vice versa. Other specific type genetic defects of beta-cell function Genetic defects in insulin action Diseases of the exocrine pancreas Endocrinopathies Drug- or chemical-induced Infections Unknown forms of immune-mediated diabetes Other genetic syndromes sometimes associated with diabetes Gestational diabetes mellitus (GDM)

5. Criteria for the diagnosis of DM 1] Symptoms of diabetes plus causal plasma glucose levels > 200 mg%. Casual defined as any time of the day without regard to time since last meal. The classic symptoms include polyuria, polydipsia, and unexplained weight loss. O r 2] FPG > 126 mg%. Fasting: no caloric intake for at least 8 h. Or 3] 2h PG>200 mg% during an OGTT: Glucose load of 75g. In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day.

6. Impaired glucose tolerance & fasting glucose IFG: > 100 mg% but < 126 mg% Near the level above which acute phase insulin secretion is lost in IV-GTT. Associated with a progressively greater risk of developing micro- & macrovascular complications. IGT: 2h levels of BG after OGTT between 140 mg% to 200 mg%. IGF & IGT are risk factors for future diabetes. Associated with syndrome X (insulin resistance syn)

7. סיבוכים ארוכי טווח של סכרת (1) Retinopathy: potential loss of vision Nephropathy: potential renal failure Peripheral neuropathy: Foot ulcer Amputation Charcot joints Autonomic neuropathy: Gastrointestinal Genitourinary Cardiovascular Sexual dysfunction

8. סבוכים ארוכי טווח של סכרת (2) Vascular disease: Cardiovascular Peripheral vascular Cerebrovascular Hypertension dislypidemia Periodontal disease Psychosocial dysfunction

9. Changes of the new classification Elimination of insulin dependent vs. insulin independent Type 1 & type 2: Type 1: b-cell destruction with tendency to ketoacidosis, d/t autoimmune process with autoantibodies or without (type 1 idiopathic) Elimination of malnutrition-related diabetes Addition of impaired fasting glucose (IFG) to the entity of IGT.

10. Type 1 diabetes Cellular-mediated immune destruction of the b-cells HLA association (HLA class II): DQA, DQB, DRB Autoantibodies: insulin autoantibodies (IAA) Islet cells autoantibodies (ICA) anti Glutmic acid decarboxylase (GAD 65 ) antibodies to tyrosine phosphatase IA-2 & IA-2b Young age/ lean habitus/ ketoacidosis/ autoimmune Idiopathic diabetes No autoimmunity, no HLA predisposition (but inherited) Most are of African or Asian origin Insulin requirement may come and go

11. Diabetic ketoacidosis DEFINITION  Blood glucose > 250 mg%  Ketonemia  pH < 7.30 and standard bicarbonate < 15 meq/L

12. Diabetic ketoacidosis [1] Dehydration Osmotic diuresis (glycosuria)NS 20cc/kg 1 st hour vomitingmaintenance + deficit Insensible loss (Kussmaul breathing, fever) Hyperglycemia InsulinopeniaInsulin 0.1 Unit/kg/hour Insulin resistance (acidosis) Counterregulatory hormones

13. Diabetic ketoacidosis [2] Hyponatremia Water shift to ECFNS 1 st hour Pseudohyponatremia0.5 NS later Hyperkalemia AcidosisK < 3.5 meq/L: 40 meq/L pre renal azotemiaK 3.5-5 meq/L: 30 meq/L K 5-5.5 meq/L: 20 meq/L Hypophosphatemia Phosphaturia½ KCL, ½ KPO4

14. Diabetic ketoacidosis [3] Acidosis Free fatty acids (lypolysis)Insulin Lactic acidosisRehydration Hyperlipidemia LypolysisInsulin

15. Genetic defects of b-cell function Monogenetic defects: autosomal dominant pattern (MODY) Onset: before 25 y, mild hyperglycemia 1] Mutations in hepatocyte nuclear factor (HNF)-1a, chromosome 12 (MODY 3) 2] Mutations in glucokinase, chromosome 7 (MODY 2) 3] Mutations in HNF-4a, chromosome 20 (MODY 1) 4] Point mutations in mitochondrial DNA (mainly position 3243 in tRNA of leucine gene, similar to MELAS syndrom) 5]Impaired conversion of proinsulin to insulin (IGT) 6] Mutant insulin molecule with impaired receptor binding

17. GLUCOKINASE: YING & YANG INTERPLAY Glucokinase loss-of-function mutations: Decreased G phosphorylation decreased Insulin secretion MODY 2. Glucokinase gain-of-function mutations: Hyperinsulinism: Glaser et al: NEJM 1998;338,226. Autosomal dominant (3 generations) Val455Met mutation In vitro study: increased affinity of glucokinase for G higher rate of glycolysis at low G concentrations GSIR threshold: about 40 mg% Sequels: T1DM at later age

18. IPF1 (PDX1) deficiency linked to MODY4 Stoffers et al: nature genetics 1997;17,138. Extended-family pedigree (6 generations) Onset of DM: 35 y (range 17-67 ) Heterozygous individuals: 6/8 Rx of diet or OH No signs of ketosis or severe insulin deficiency

19. Genetic defects in insulin action Murations of the insulin receptor with subsequent insulin resistance (acanthosis nigricans, virilization, PCOS) Leprechaunism: characteristic facial features, fatal Rabson-Mendelhall syndrome: abnormalities of teeth and nails, pineal gland hyperplasia Lipoatrophic diabetes: a defect in the post-receptor signal transduction pathway.

20. Diseases of the exocrine pancreas Pancreatitis Trauma \ pancreatectomy Neoplasia Cystic fibrosis Hemochromatosis Fibrocalculous pancreatopathy

21. Other genetic syndromes Down’s syndrome (autoimmune diseases) Kleinfelter syndrome Turner syndrome Wolfram’s syndrome (DIDMOD)

22. Enedocrinopathies Acromegaly Cushing syndrome Glucagonoma Pheormacytoma Hyperthyroidism Somatostatinoma Aldosteronoma

23. Drug- or chemical-induced Vacor (rat poison): permanently destroy b-cells Pentamidine: permanently destroy b-cells Nicotinic acid: impair insulin action Glucocorticoids: impair insulin action Interferon-a: induce antibodies’ positive diabetes

24. I n f e c ti o n s Congenital rubella CMV Coxsackie B virus Adenovirus Mumps