Leptin Levels, β-Cell Function, and Insulin Sensitivity in Families with Congenital and Acquired Generalized Lipoatropic Diabetes1

Abstract

Lipoatropic diabetes (LD) designates a group of syndromes characterized by diabetes mellitus with marked insulin resistance and either a localized or generalized absence of adipose tissue. In this study, we evaluated plasma leptin levels in subjects with congenital generalized lipoatropic diabetes (CGLD, n = 11) or acquired generalized lipoatropic diabetes (AGLD, n = 11), and assessed correlations between leptin levels 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 levels 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 were significantly correlated with body mass index, insulin levels, and HOMA beta-cell function, and inversely correlated with insulin sensitivity in control subjects but not in subjects with generalized LD. In conclusion, decreased leptin levels were observed in subjects with generalized LD, with a trend towards lower levels in the acquired than in the congenital form (P = 0.06). The temporal relationship between the decrease 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 lipoatrophy.

Insulin Resistance in Children

“…In addition, these patients may have acanthosis nigricans and hepatic steatosis, which increases the risk to develop cirrhosis, prominent musculature, precocious secondary sexual development, and, in some cases, intellectual impairment (16, 18). IR has an early onset in these patients (19). Studies conducted on the correlation between IR and lipoatrophy do not have an univocal answer concerning an hypothetical altered insulin receptor expression, function and signaling involved in its pathogenesis (20).…”

20 YEARS OF LEPTIN: Role of leptin in human reproductive disorders

“…Similar to patients with congenital leptin deficiency, patients with lipodystrophy, either due to a congenital or an acquired destruction of adipose tissue, are also hypoleptinemic and insulin resistant (Pardini et al 1998, Nagy et al 2003. In addition to improving insulin resistance (Lee et al 2006, Ebihara et al 2007, Brennan et al 2009, leptin may also have beneficial effects on reproductive function of lipodystrophic women (Musso et al 2005).…”

“…In addition to improving insulin resistance (Lee et al 2006, Ebihara et al 2007, Brennan et al 2009, leptin may also have beneficial effects on reproductive function of lipodystrophic women (Musso et al 2005). Women with lipodystrophy usually have enlarged polycystic ovaries, hyperandrogenism, amenorrhea, and infertility (Pardini et al 1998, Musso et al 2005. In an open-label study of 10 women with generalized lipodystrophy, leptin treatment for 12 months decreased serum free testosterone concentrations by 50%, increased sex hormonebinding globulin (SHBG) concentrations, and increased the LH response to GnRH (Musso et al 2005).…”