Human Insulin Analog–Induced Lipoatrophy

OBJECTIVE—To characterize the pathophysiology of recombinant human insulin-induced lipoatrophy. RESEARCH DESIGN AND METHODS—We performed immunologic laboratory evaluation and skin testing for different insulin analogs and diluents in patients with type 1 diabetes and severe insulin-induced local lipoatrophy. Subcutaneous adipose tissue biopsies of areas of acute (7 days) and chronic insulin administration were examined. Topical sodium cromolyn was applied twice a day to atrophic areas and prophylactically to new sites of insulin administration. RESULTS—Subcutaneous adipose biopsies showed an elevated population of tryptase-positive, chymase-positive degranulated mast cells. Of five patients treated with topical sodium cromolyn, none had new lipoatrophic sites and four showed improvements in old lesions. CONCLUSIONS—Tryptase-positive/chymase-postitive mast cells, known to be sensitive to sodium cromolyn, may contribute to the destructive immune process mediated in response to exogenous insulin. Mast cell stabilizing therapy with topical cromolyn may reverse early and prevent new lipoatrophic lesions.