Cromolyn Reverses Insulin Analog-Induced Lipoatrophy

Mast cell stabilizing therapy with topical cromolyn can reverse early injection-site lipoatrophy induced by human insulin analogs, and prevent further lesions. Dr. Allison B. Goldfine from the Joslin Diabetes Center, Boston, Massachusetts states that, “The problem of local lipoatrophy is uncommon, "and the kinetic advantages of insulin analogs to patients with diabetes outweigh this small risk."  "However, we would be pleased if our therapy provided a means to treat the lesions in those that develop this rare complication."

Dr. Goldfine and colleagues described the pathophysiology of recombinant human insulin-induced lipoatrophy and its response to treatment with topical cromolyn in three women and two men with severe local atrophy.

Subcutaneous biopsies from acute and chronic injection sites showed increased numbers of interstitial and perivascular mast cells with active degranulation in all cases and prominent eosinophils in three cases, the investigators report.

"Topical cromolyn sodium was applied twice a day to atrophic areas and prophylactically to new sites of insulin administration," they explain.

None of the patients developed new lipoatrophic lesions after using topical cromolyn, the researchers note, and four of the five showed significant improvement of lipoatrophy, with complete resolution after only 4 weeks in one patient.
The only patient whose lesions did not improve showed progression of her lesions. She had the longest time interval from initial appearance of lipoatrophy.

"Based on our findings, we hypothesize that mast cells found abundantly in areas of local insulin-induced lipoatrophy contribute pathologically to the destructive inflammatory process. These were tryptase-positive/chymase-positive mast cells, a subtype known to be sensitive to cromolyn but resistant to glucocorticoids," the investigators conclude.
"Physicians are choosing to use our findings and treat empirically with the cromolyn without biopsy," Dr. Goldfine said. "This is not an unreasonable approach."

Future long-term studies, Dr. Goldfine concluded, "will help determine whether these patients will need to use topical cromolyn permanently to prevent lipoatrophy lesions, or whether after some period of treatment with cromolyn, discontinuation with or without an additional form of intervention may halt the process."
Diabetes Care 2008;31:442-444.

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