Pathophysiology of Recombinant Human Insulin-Induced Local Lipoatrophy

Ximena Lopez; Castells, Mariana C.; Velazquez, Elsa F.; Ricker, Alyne; Lin, Debby A.; Mun, Edward C.; Goldfine, Allison B.
June 2007
Diabetes;Jun2007 Supplement 1, Vol. 56, pA158
Academic Journal
Insulin-induced lipoatrophy has become uncommon after the introduction of purified recombinant human insulin. It can be cosmetically devastating and the loss of subcutaneous tissue sites for insulin administration complicates therapy. We report 5 cases of local lipoatrophy associated with modified insulin analogs. Patients had type 1 diabetes and were 14-34 years of age at presentation. Local lipoatrophy was associated with use of lispro (n=3), aspart (n=2), NPH (n=1) and glargine (n=1). In 2 cases local lipoatrophy was clinically apparent with both lispro and aspart. Two of 5 patients had additional autoimmune disease including Graves Disease and hypothyroidism. No patient had measurable latex IgE antibodies. Serum protein electrophoresis, erythrocyte sedimentation rate, antinuclear antigen, rheumatoid factor, tryptase, TNF-α and complement levels C3, C4 and CH50 were all normal. All of the patients had negative human insulin IgE but modestly elevated human insulin IgG antibodies (range 11-141 µg/ml, normal <9). Allergy skin testing was performed in 4 patients and no local reaction was demonstrated to either insulin or diluent. Subcutaneous fat biopsies were available in 3 patients. Biopsies from non-affected areas were used as control. All the biopsies from affected areas showed lobular adipose tissue atrophy with focal fibrosis and a variable degree of angiocentric and lobular lymphocytic panniculitis. Eosinophils were prominent in two cases. An elevated mast cell population identified with tryptase, chloroacetate esterase (CAE) and c-kit stains, was present in perivascular and interstitial location in all cases. A variable degree of active mast cell degranulation was seen. Direct immunofluorescence for IgG, IgA, IgM, C3 and fibrin were all negative. The high number of recent cases of local lipoatrophy suggests that local allergic reactions may be more prevalent with insulin analogs. Mast cells may contribute to the destructive inflammatory process and may potentially be a target for therapeutic intervention.


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