Insulin-induced lipoatrophy, a “rare, albeit feared condition,”1 can be defined as an “immune-mediated loss of subcutaneous adipose tissue at insulin administration sites.”2

Lipoatrophy was a common complication of insulin therapy prior to the development of purified insulin in the 1970s.3 Previously, it affected 10% to 55% of patients using animal-derived insulins.4

Today, the condition is rare. One study of 220 patients with diabetes found that only 1.4% had lipoatrophy, although higher percentages suffered from other types of adipose complications, such as lipohypertrophy.5

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Since lipoatrophy continues to affect patients taking insulin analogs, it continues to pose a clinical challenge because it leads to “erratic insulin absorption at affected areas,” as well as “distressing cosmetic issues.”2

Insulin-induced lipoatrophy is complex and caused by several immune responses. For example, it appears to be mediated by a local high production of tumor necrosis factor-α, which works against differentiation of adipocytes in the subcutaneous tissue.3 For this reason, it may respond to glucocorticoids.1,3

Another pathophysiological mechanism is increased degranulating tryptase/chymase-positive mast cells, which have been found in biopsies taken from insulin-induced lipoatrophic sites.6

In a previous small case series, topical cromolyn sodium, administered twice daily, was found to be efficacious therapy for this condition.6

A more recent analysis of data from 24 patients with insulin-induced lipoatrophy analyzed the response to cromolyn, as well as to other therapeutic interventions.

In the course of studying treatment response, the researchers also analyzed the types of insulin most commonly associated with lipoatrophy.2 (Table 1)

Table 1

Type of Insulin

Number of Patients Experiencing Insulin-Induced Lipoatrophy





Regular human insulin


NPH insulin






Multiple insulin preparations


Common affected insulin injection sites were abdomen (n = 6), thighs (n = 5), and buttocks (n = 3), with sizes ranging from 2 x 2 cm to 8 x 10 cm. Eight patients reported multiple lipoatrophic sites.2

Of the patients analyzed, two were treated with glucocorticoids. These patients did not experience partial or full symptom resolution.