DIABETES MELLITIUS

Cells and Molecules

Clinical Application

Presented 9/6/02

By

M. Grant Ervin MD,MHPE,FACEP

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

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

What are the abnormalities?

• Thirst

• Weakness

• Low blood pressure

• Fast heart rate

• Fast respiratory rate

Simultaneous Diagnostic, Therapeutic, and Rescuscitative

Measures

Pulse OxEKGIV line, blood for I-stat, extra tubes to be

determinedCardiac monitor, BP monitorPhysical Exam significant dry mucus

membranes and abnormal vital signs as stated

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

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

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

Overall metabolism is stuck in every tissue continuing its catabolic state producing

more fuel despite increase glucose. Insulin/ glucagon

ration is unbalanced

Therapeutic Measures

• Fluids

• Insulin

• Correct electrolyte deficiencies

• Look for precipitating causes

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