Medical Pharmacology Chapter 29:  Diabetes

• Type II diabetes represents a group of milder forms of diabetes that occurs mainly in adults.

• Endogenous insulin is sufficient to prevent ketoacidosis; however, abnormal insulin secretion and resistance to insuling action at tissues occur.

• Obesity: common risk factor

• NIDDM patients exhibit a deficiency in pancreatic B cell response to glucose.

  • The impaired response is worsened by hyperglycemia.

• Pathophysiological Phases:

  1. Plasma glucose: normal -- elevated insulin levels

  2. Elevated insulin levels -- postprandial hypoglycemia

  3. Insulin or systems to change -- reduced insulin secretion causes fasting hyperglycemia him (diabetes)

• Clinical Presentations:

  • NIDDM: appears in middle age or later; mainly in overweight patients

  • Gradual onset of symptoms

    • Presenting symptoms

      1. Extreme hyperglycemia

      2. Hyperosmolality

      3. Volume depletion

      4. CNS symptoms (ranging from clouded sensorium to coma)

         1. Seizure activity (Jacksonian)

         2. Transient hemiplegia

      5.  Infections: pneumonia and gram-negative sepsis (common, associated with very negative prognosis)

  • Patients with NIDDM usually do not develop ketoacidosis

  • Patients with NIDDM may develop hyperosmolar, nonketotic coma

    • Syndrome properties

      • Results from sustained hyperglycemia diuresis if patient cannot drink enough water to keep up with urinary fluid loss

      • Complete manifestation occurs when volume depletion decreases urine output

    • Hyperosmolar coma can occur in insulin-dependent diabetics if the insulin given is sufficient to prevent ketosis but not enough to control hyperglycemia.

  • Hyperosmolar coma can also be caused by:

    • Peritoneal/hemodialysis

    • Tube feeding of high-protein formulas

    • High-carbohydrate in fusion loads

    • Osmotic agents (mannitol and urea)

  •   Prognosis:

    • Mortality rate and hyperosmolar coma may be  > 50%

  • Treatment of hyperosmolar coma states

    • large amounts of intravenous fluids (average fluid deficit: 10-11 liters.

    • Insulin: more rapid control hyperglycemia

    • Potassium salts (counteract intracellular shifted plasma K⁺)

    • Sodium bicarbonate (if lactic acidosis present)

    • Antibiotics

• Type II diabetes treatment Overview

  1. Diet

  2. Weight reduction

  3. Drugs other than insulin, if diet in weight reduction are inadequate.

  4. Insulin may be required

Karam, J. H., Pancreatic Hormones and Antidiabetic Drugs, in Basic and Clinical Pharmacology, (Katzung, B. G., ed) Appleton-Lange, 1998, pp 684-703

Foster, D. W., Diabetes Mellitus, In Harrison's Principles of Internal Medicine 14th edition, (Isselbacher, K.J., Braunwald, E., Wilson, J.D., Martin, J.B., Fauci, A.S. and Kasper, D.L., eds) McGraw-Hill, Inc (Health Professions Division), 1998, pp 2060-2080