1. Lecture 25 Insulin Dependent Diabetes Mellitus Type 1 Diabetes Juvenile Onset Diabetes

2. 500 BC Frequent urination Rapid loss of weight Unquenchable thirst “Sweet” breath Death within a few weeks –Diabetes Urine contains sugar –Mellitus

3. Hypoinsulinemia Think about what insulin does –Not just anabolic, also anti-catabolic Prevents –Glycogenolysis –Proteolysis –Lipolysis Stimulates –Glucose uptake and disposal

4. Lack of Insulin Poor glucose uptake into cells –But not zero, and only muscle/WAT affected –Will elicit a bit of hyperglycemia Poor lipogenesis & glycogenesis –Of little consequence Massive, uncontrolled lipolysis –Huge release of fatty acids into the bloodstream And glycerol –High rates of fatty acid oxidation Inhibits glucose oxidation, glucose  lactate –High rates of ketone body production Inhibts glucose metabolism in the brain Uncontrolled proteolysis –Breakdown of tissues –Release of amino acids into bloodstream

5. Lipolysis & Proteolysis Weight loss –Dangerous loss of essential protein Increasing hyperglycemia –High rates of gluconeogenesis Glycerol, amino acids & lactate as substrates Fatty acid oxidation stimulating pyruvate carboxylase Low insulin, increased cAMP  increased F16BPase –Low rates of glucose disposal Blood acidity rises –Fatty acids, lactate, ketone bodies all acidic –Ketoacidosis Ketone bodies decarboxylate –Acetone lost on breath

6. Hyperglycemia Glycosylation increases –But long term Loss of glucose in urine –Glucose reabsorbtion by kidneys reduced above [glucose] blood =10 mM Osmolality of blood changes –Draws water out of the tissues –Massive thrist Increased water intake –Increased urination –Loss of electrolytes

7. Treatment Insulin –Discovered & first used in 1922 Tight control to avoid complications –Blood glucose monitoring –Tailored insulin injections Long and short acting forms –Risk of hypoglycemia Hypoglycemia unawareness