2. Introduction Function of the Endocrine Pancreas Insulin Glucagon Incretins Somatostatin Diabetes Mellitus Type 1 Diabetes Type 2 Diabetes Measures of Glycemic Control Ketone Testing

3. Hypoglycemia Hypoglycemic Disorders Inborn Errors of Carbohydrate Metabolism Defects in Galactose Metabolism Defects in Fructose Metabolism Lactic Acidosis

4. Carbohydrates are major constituents of physiological systems. The concentration of glucose in blood is normally controlled within narrow limits

5. Function of the Endocrine Pancreas as both an endocrine and exocrine organ in the control of carbohydrate metabolism Exocrine Amylase The endocrine pancreas secretes four hormones

6. Disease states occur when insulin concentrations are inappropriate for given blood glucose levels.

8. Processing of proinsulin to insulin. Green circles represent cysteine residues that participate in disulfide bonding.

10. Diabetes Mellitus: Introduction a group of diseases in which blood glucose levels are elevated Deficient insulin secretion and/or abnormal action. the most common set of disorders of carbohydrate metabolism The prevalence of diabetes 33% of males and 39% females A chronic disease, responsible for significant morbidity, mortality & cost. People with diabetes are at least two to four times more likely to have heart disease and cerebrovascular disease

11. Criteria for the diagnosis of diabetes Pre-diabetes Impaired fasting glucose Impaired glucose tolerance at increased risk for cardiovascular & cerebrovascular diseases.

12. Diagnosis of Pre-Diabetes and Diabetes Mellitus

13. Diagnosis of Gestational Diabetes Mellitus

14. the metabolic syndrome A cluster of clinical disorders Increased risk of cardiovascular disease & of developing diabetes The criteria defining the metabolic syndrome the presence of three or more of the following: impaired fasting glucose blood pressure ≥ 130/85 mmHg Waist circumference > 102 cm in men and > 88 cm in women, Serum triglycerides ≥ 150 mg/dL (1.695 mmol/L HDL-cholesterol < 40 mgfdL (1.036 mmol/L) in men and < 50 mg/dL (1.295 mmol/L) In women. Most commonly, these individuals are insulin resistant and have smaller, denser, more atherogenic LDL-cholesterol particles.

15. The most common forms of diabetes are type 1 and type 2 diabetes (Table). Uncommon causes of diabetes (Table)

16. Classification of Diabetes Mellitus

17. Classification of Diabetes Mellitus (Cont'd)

19. Characteristics of Type 1 and Type 2 Diabetes Mellitus

20. Type 1 Diabetes Antibody markers of beta cell destruction are commonly present before and at the time of the onset of the diabetes antibodies to the 65-kDa isoform of glutamic acid decarboxylase (GAD65) insulin autoantibodies (IAA) and islet cell antigen 512 autoantibodies (ICA512l. ICA512 are autoantibodies to parts of the tyrosine phosphatase IA-2 antigen. Greatest risk High titers of multiple autoantibodies. Detection of at least two autoantibodies is associated GAD65 has the highest sensitivity (91%) IAA are more common in young children who develop type I diabetes, whereas GAD65 is more common in adults.

21. The 'pre-diabetes' period of gradual and progressive beta cell destruction can last for months, years or decades First phase insulin release

22. Type 2 Diabetes

23. Measures of Glycemic Control Glycosylated hemoglobin (GHb) is formed nonenzymatically by the two-step reaction

25. HbA 1C definition as the hemoglobin A that is irreversibly glycosylated at one or both N-terminal valines of the p-chains of the tetrameric hemoglobin molecule, including hemoglobin that may also (but not solely be glycosylated on lysine residues. an index of average blood glucose levels over the past 2-4 months.

26. Correlation Between HbA 1C and Mean Plasma Glucose Levels

27. Glycemic Goals

28. GHb assays vary in reliability in the presence of a variety of factors. carbamylated hemoglobin can occur with uremia hypenriglyceridemia and hyperbilirubinemia, and salicylates Hemoglobinopathies Transfusions Chronic alcohol or opiate use, iron deficiency and lead poisoning Vitamins C and E sample storage effects Hemolysis splenectomy, people without diabetes have HbA 1C levels between 4-6%.

29. glycosylated proteins or glycosylated albumin glycemic control over narrower periods of time. useful in patients for whom HbA)( assays are inaccurate hemoglobinopathies and hemolytic anemias However, their clinical utility has not been firmly established.

30. Ketone Testing beta-hydroxybutyric acid, acetoacetic acid and acetone Particularly important for individuals with type 1 diabetes mellitus to detect ketosis. determining the etiology of hypoglycemic disorders The ratio of beta-hydroxybutyrate acid to acetoacetic acid is greatly increased in DKA Diabetic ketoacidosis (DKA)