Adverse Reactions to Insulin Therapy

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The most common side effect associated with insulin therapy is hypoglycemia, which may result in such CNS symptoms as tremors, lethargy, hunger, confusion, motor and sensory deficits, seizures, and unconsciousness. Adrenergic manifestations include anxiety, palpitations, tachycardia, and diaphoresis. In many cases, diabetics are aware that hypoglycemia is developing, and prompt administration of oral carbohydrates (e.g., fruit juice or glucose tablets) can restore normoglycemia. In more severe cases (e.g., unconsciousness, seizures), intravenous glucose or intramuscular glucagon is required to reverse the hypoglycemia.

Another frequent side effect of insulin therapy is weight gain. Some is due to increased caloric storage of glucose by insulin, and some is due to renal sodium retention resulting in fluid retention and edema. These effects can synergize with oral agents that are often coad-ministered with insulin, particularly sulfonylureas and thiazolidinediones.

Other complications arising from insulin therapy are uncommon. Sometimes, diabetics treated with exoge nous insulin develop insulin-binding immunoglobulins, although the clinical significance of these antibodies remains unclear. Allergic reactions due to the use of animal-derived insulins has subsided since the use of recombinant DNA-derived human insulin became widespread. Over time, repeated subcutaneous injections of insulin can cause local lipodystrophy (lipohypertrophy or lipoatrophy), which may alter the pharmacokinetics of insulin absorption from this site. Also, hypokalemia can follow acute insulin administration, an effect that is due to the stimulation of Na+-K+-ATPase (adenosine triphosphatase) with its resultant redistribution of K+ to the intracellular compartment. This property of insulin is sometimes used in the emergency treatment of hy-perkalemia.

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