Nursing Pharmacology Chapter 29:  Diabetes

• Overview of clinical presentation: Type I diabetes:

   

  • Type 1 diabetes:  Sam's Story

    Williamson, S "Type 1 diabetes:  Sam's story https://www.youtube.com/watch?v=2bhcqzPq15o

  • Onset:  IDDM is typically before the age of 40.

    • Peak incidence: age 14

  • Most symptoms secondary to hyperglycemia.

    • Polyuria (excessive urination)

    • Polydipsia (excessive thirst)

    • Polyphagia (excessive or voracious eating)

  • First event may be metabolic:

    •  Acute metabolic decompensation: diabetic coma

  • First event may be degenerative, e.g. neuropathy

  • Diabetic metabolic abnormalities due to diabetic ketoacidosis.

    • Relative or complete insulin deficiency

    • Relative or significant glucagon access

    • Metabolic decompensation may follow an increase in glucagon/insulin ratio.

      • Causes of diabetic ketoacidosis

        • Requires insulin deficiency and a relative/absolute increase in glucagon

        • Precipitated by:

          • Cessation of insulin intake.

            • Glucagon increases secondary to insulin withdrawal.

          • Physical stress (infection, surgery) and/or emotional stress, even with continued insulin treatment.

            • Glucagon releases enhanced by increased circulating catecholamines.

            • Epinephrine may also block:

              1. Release of residual insulin present and some patients with IDDM.

              2. Insulin-induced glucose transport in the periphery.

      • Effects of these hormonal changes

        • Maximal gluconeogenesis with impairment of peripheral glucose utilization resulting in severe hyperglycemia.

      • Enhanced gluconeogenesis and the role of glucagon

        • Glucagon enhances gluconeogenesis by:

          • Causing a reduction in fructose-2,6-bisphosphate, a metabolic intermediate that stimulates glycolysis and blocks gluconeogenesis.

          • Hyperglycemia results.

            • Consequences of hyperglycemia:

              • Osmotic diuresis.

              • Volume depletion/dehydration, characteristic of ketoacidotic condition.

      • Hormonal changes i.e. insulin deficiency with the relative/absolute increase in glucagon activate ketogenic process, leading to metabolic acidosis

        • Ketosis

          • Free fatty acids from fat stores are primary substrates for ketone body formation

          • High plasma free fatty acid levels are required for significant ketogenesis

          • Normally the concentration of plasma free fatty acids are lowered by the liver where fatty acids are reesterified and stored as hepatic triglyceride or converted into VLDL -- unless the system for hepatic oxidation of fatty acids becomes activated.

            • Release of free fatty acids is increased by insulin deficiency;

            • Accelerated hepatic fatty acid oxidation is caused by glucagon-- by acting on carnitine palmitoyltransferase enzymes (CPT)

          • Activation of carnitine palmitoyltransferase I (CPT I), normally inactive, is activated by uncontrolled diabetes (or starvation)

          • Activation of carnitine palmitoyltransferase I (CPT I) allows long-chain free fatty acids to reach beta-oxidative enzymes localized in the mitochondrial matrix where ketone body production occurs.

    • Clinical Manifestations of Ketoacidosis

      • Stages

        1. Anorexia, nausea, vomiting.

        2. Increased urine formation; abdominal pain.

        3. Kussmaul respiration (air hunger); signs of volume depletion; leukocytosis.

        4. Later stages: altered consciousness/coma.

      • Hypertriglyceridemia

      • Prerenal azotemia

      • Pancreatitis

    • Diagnosis of ketoacidosis (in a patient with insulin-dependent diabetes)

      • Positive urine test for glucose and ketones

      • Strong plasma reaction using ketone reagent strips following dilution exceeding 1:1 (a positive test without dilution may indicate starvation as a cause)

        • The other common ketoacidotic state (other than diabetes) is alcoholic ketoacidosis

    • Treatment

      • Diabetic ketoacidosis reversal requires insulin, probably using a higher dose schedule which insures receptor saturation

        • Insulin at high concentration may accelerate ketoacidosis reversal by acting through the IGF-1 receptor

      • Intravenous fluids are also required (usual fluid deficit: 3 -- 5 L.)

      • Potassium replacement always necessary.

      • Bicarbonate treatment in severely acidotic patients (pH = 7.0 or less).

    • Treatment Response

      • Plasma glucose levels fall more rapidly than plasma ketone levels. Insulin should treatment should continue until ketosis has cleared.

      • Plasma ketone values: may not be helpful in assessing clinical response.

        • Clinical state may be more accurately assessed by pH and calculated anion gap.

    • Outcome

      •  Mortality rate: about 10%

      •  Major causes of mortality:

        • Myocardial infarction

        • Infection, especially pneumonia

      •  Poor prognostic signs (on admission):

        • Hypotension

        • Azotemia

        • Deep coma

        • Cerebral edema (in children)

      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 2071-2072.