Human insulin lipoatrophy

A 51-year-old woman started to use continuous subcutaneous insulin and after 2 years the insulin was changed to insulin lispro. She developed lipoatrophy in the abdomen and buttocks 1 year later and there was an increase in the time before the bolus started to peak. Buffered regular human insulin stopped progression of the lipoatrophy. 

Other adverse reactions to insulin are lipodystrophy (atrophy or hypertrophy) at the injection sites (rare with purified pork and human insulin), after they have been used repeatedly. These are unsightly, but otherwise harmless. The site should not be used further, for absorption can be erratic, but the patient may be tempted to continue if local anaesthesia has developed, as it sometimes does. Lipoatrophy is probably allergic and lipohypertrophy is due to a local metabolic action of insulin. Local allergy also is marrifested as itching or painful red lumps. 

Before purified human insulins were available, lipoatrophy occurred in about 25% of insulin-treated patients. Improvement or resolution of lesions has been noted in most patients after changing to purified porcine insulin. 

Both pork and human insulin are definitively less immunogenic than beef insulin, producing fewer circulating insulin antibodies, but several studies have indicated no detectable change in antibody concentrations on switching from pork to human insulin or vice versa. Antibodies cause lipoatrophy and are responsible for the substantial insulin resistance seen in some patients, but both events are rare now that purified pork insulin is in common use. Interest has recently been revived in the possible contribution of antibodies in modifying metabolic control. In the short term and under hospital conditions, they are known to prolong the intravenous half-life of injected insulin and to delay the appearance in the circulation of a subcutaneously administered bolus dose. 

Atrophy of subcutaneous fat at the site of insulin injection (lipoatrophy) is probably an immune response to insulin, whereas lipohypertrophy (enlargement of subcutaneous fat depots) is ascribed to the lipogenic action of high local concentrations of insulin. Both problems are rare with more purified preparations. However, hypertrophy may occur with human insulin if patients inject themselves repeatedly in the same site. The recommended treatment is to avoid the hypertrophic areas by using other injection sites and to inject insulin into the periphery of the atrophic sites in an attempt to restore the subcutaneous adipose tissue. 

For therapy of local lumps, extravasation, etc., one should first seek to improve the injection technique. Substitution with highly purified insulin is recommended. Injection with purified insulin into the affected area may speed up resorption of the lumps. Lipodystrophy or lipoatrophy improve after switching to highly purified human or insulin lispro. Lipohypertrophy, on the other hand, often fails to respond to changes in the insulin regimen (130). Varying the injection site may help, but differences in absorption rate then have to be taken into account. 

Lipoatrophy is rare with human recombinant insulin. Two cases of lipoatrophy induced by insulin lispro during continuous subcutaneous insulin infusion have been reported (28). 

Insulin, administered subcutaneously, may cause either lipoatrophy or lipohypertrophy. Lipoatrophy is the breakdown of adipose tissue at the insulin injection site causing a depression in the skin at the injection site and occasionally at distant sites also. It may be the result of an immune response or the use of less than pure insulin. Some findings suggest that total lipodystrophy syndrome results from the inflammatory destructive process of adipose tissue (Yanagawa et al., 1990). Injection of human or purified porcine insulin into the site over a 2-4-week period may result in subcutaneous fat accumulation. 

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