Discussion

Lipoatrophy is usually a complication of T1DM treatment. Lipoatrophy was commonly seen with old insulins (bovine and porcine). It is now rarely observed since the introduction of highly purified insulins and insulin analogues.

In 2005, Ampudia-Blasco reported the case of a 39-year-old patient with T1DM who developed lipoatrophy at the injections sites with insulin Glargine.1 Most of the other previously described cases were associated with the use of insulin Lispro. A 10-year-old Caucasian girl from Yale University developed localised lipoatrophy of the subcutaneous tissue of the anterior abdominal wall a year after treatment with continuous subcutaneous insulin infusion (CSII) using Lispro insulin.2 The lipoatrophy did not progress further after switching to buffered human regular insulin using the same MiniMed CSII pump. Therefore, the authors attributed the cause to Lispro insulin. However, lipoatrophy was also reported with CSII which did not regress after changing Lispro to buffered human insulin.3 There was local hyperproduction of tumour necrosis factor α from macrophages leading to differentiation of adipocytes resulting in lipoatrophy. It was therefore hypothesised that Teflon cannulae used in the pump system may have induced the local immune reaction.3 Another case was reported with lipoatrophy induced by Lispro insulin but not in combination with pump therapy.4 Most recently, a 13-year-old girl with injection-site lipoatrophy was described, also in association with Lispro insulin.5

The pathogenesis of lipoatrophy is still poorly understood. The suggested mechanisms are: repeated mechanical trauma from the injections, cryotrauma from refrigerated insulin or immune mediation. Many studies have demonstrated an association between high insulin antibodies and lipoatrophy. In a study conducted at the diabetes clinic of the University Children's Hospital in Munich, Germany, 112 children were randomly recruited for measurement of insulin antibodies.6 Lipoatrophy was found in four children who had significantly high insulin antibody levels. This study concluded that there is a strong association between insulin antibody levels and lipoatrophy, which implies immunity against insulin is a factor in the development of lipoatrophy. Another report in 1998 also described a significantly high insulin antibody level in an adult with diabetes.7 We observed high levels of insulin antibody in three of our cases.

The management of lipoatrophy has not yet been well established. Suggested treatments include injecting insulin around the atrophic sites in combination with dexamethasone.8 In two of our patients, lipoatrophy resolved after changing the injection sites alone, suggesting that local factors could be contributing to the development of lipoatrophy. However, in the other two children lipoatrophy developed at the new injection sites but resolved after we changed the insulin preparations. This suggests that immunity against insulin might be a contributing factor. HbA1c decreased after resolution in two of our patients but remained the same in other two. HbA1c decreased in only one of the two patients where lipoatrophy resolved after changing sites, suggesting that poor absorption from the site with lipoatrophy might be contributing to the high HbA1c levels in at least one of those patients. In the other two patients whose lipoatrophy resolved only after changing insulin preparation, HbA1c improved in only one, suggesting that immunity might have caused poor insulin absorption from the local lipoatrophy site.