Genetic Disorders of Insulin Resistance

These genetic defects may cause diabetes varying from mild to severe. Marked hyperinsulinemia activates epidermal growth factor receptors in skin, resulting in acanthosis nigricans, a darkening of skin folds at the nape of the neck or in the axilla. Marked hyperinsulinemia stimulates ovarian steroidogenesis, which can result in enlarged ovaries and a virilizing syndrome. This condition provided insight into the connection of insulin resistance to polycystic ovarian syndrome, which is now routinely treated with metformin to attenuate hirsutism and stimulate ovulation. The genetic defects in patients with generalized lipoatrophy have not been fully defined, but these patients are extremely insulin resistant because energy substrates can be stored only in liver and muscle. Impairment in fatty acid storage compromises muscle uptake and glucose oxidation.

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