LEPTIN LEVELS, BETA-CELL FUNCTION, AND INSULIN SENSITIVITY IN FAMILIES WITH CONGENITAL AND ACQUIRED GENERALIZED LIPOATROPIC DIABETES

Lipoatropic diabetes (LD) designates a group of syndromes characterize d by diabetes mellitus with marked insulin resistance and either a loc alized or generalized absence of adipose tissue. In this study, we eva luated plasma leptin levels in subjects with congenital generalized li poatropic diabetes (CGLD, n = 11) or acquired gener alized lipoatropic diabetes (AGLD, n = 11), and assessed correlations between leptin lev els and estimations of insulin secretion and insulin sensitivity using homeostasis model assessment (HOMA). Leptin levels were 0.86 +/- 0.32 , 1.76 +/- 0.78, and 6.9 + 4.4 ng/mL in subjects with CGLD, AGLD, and controls (n = 19), respectively (ANOVA P < 0.0001). Specific insulin l evels were 154 +/- 172, 177 +/- 137 and 43 +/- 22 pmol/L, respectively (P < 0.0001). Insulin sensitivity was significantly decreased in both groups with LD (P < 0.0001), whereas HOMA beta-cell function was not significantly different when compared with controls. Leptin levels wer e significantly correlated with body mass index, insulin levels, and H OMA beta-cell function, and inversely correlated with insulin sensitiv ity in control subjects but not in subjects with generalized LD. In co nclusion, decreased leptin levels were observed in subjects with gener alized LD, with a trend towards lower levels in the acquired than in t he congenital form (P = 0.06). The temporal relationship between the d ecrease in leptin levels and the development of lipoatrophy should be investigated in at-risk young relatives of subjects with the acquired forms to assess the usefulness of leptin levels as a marker of lipoatr ophy.