2. DIABETES MELLITIUS Cells and Molecules Clinical Application Presented 9/6/02 By M. Grant Ervin MD,MHPE,FACEP

3. Objectives Correlate clinical presentation of patient with DKA with occurrences on cellular level Describe mechanisms by which glucagon and insulin regulate glycolysis Discuss therapeutic measures used to treat the patient in DKA and the cellular impact

4. A 45 year old male is brought into the ED c/o increased thirst, dizziness, weakness for the past week. He denies any medical problems, medications, allergies. BP – 100/60, RR-24, HR – 120, Temp.99.9 F

5. What are the abnormalities? Thirst Weakness Low blood pressure Fast heart rate Fast respiratory rate

6. Simultaneous Diagnostic, Therapeutic, and Rescuscitative Measures Pulse Ox EKG IV line, blood for I-stat, extra tubes to be determined Cardiac monitor, BP monitor Physical Exam significant dry mucus membranes and abnormal vital signs as stated

7. Causes of Elevated Anion Gap Metabolic Acidosis Carbon monoxide/cyanide exposure Alcohol Touluene Methanol uremia DKA Paraldehyde ingestion Isoniazid/Iron Lactic acidosis Ehtylene glycol salicylates

8. Cellular Correlations Elevated glucose levels secondary to decreased insulin, liver has diminished enymatic capacity to remove glucose Decreased glucokinase activity Loss of insulin’s action on key enzymes of glycogenesis and the glycolytic pathway Liver stuck in gluconeogenesis fueled by substrate from body protein degradation

9. Cellular Correlations (con.) Muscle fails to take up glucose with decreased insulin Adipose tissue is stimulated to lipolysis due to low insulin/glucagon ration Leads to increased blood levels fatty acids Accelerated ketone body production Metabolic acidosis Increase respiratory rate is trying to correct acidosis

10. Overall metabolism is stuck in every tissue continuing its catabolic state producing more fuel despite increase glucose. Insulin/ glucagon ration is unbalanced

11. Therapeutic Measures Fluids Insulin Correct electrolyte deficiencies Look for precipitating causes

12. Summary In Insulin Dependent and Non-Insulin Dependent Diabetes the insulin/ glucagon ratio is vital in intracellular glucose control Therapeutic measures are directly tied to what is occurring on a cellular level