The degree of hyperinsulinemia and impaired glucose tolerance predicts plasma leptin concentrations in women only: A new exploratory paradigm

Plasma leptin has been shown to correlate positively with many indices of o besity, as well as insulin resistance. For a given body weight, the levels are higher in women than in men, but the reasons for this difference are no t clear. Insulin has been shown to stimulate leptin production by adipose t issue in vivo and in vitro. Previous studies have reported that leptin leve ls are similar in diabetic and nondiabetic individuals. However, these stud ies were not performed in newly diagnosed diabetics, and other variables (s uch as gender) could have confounded the results. Therefore, the goal of th e present cross-sectional study is to examine the effect of metabolic varia bles (such as glucose and insulin) on plasma leptin concentrations in men a nd women separately. We measured leptin levels in 48 subjects (17 with newl y diagnosed type 2 diabetes mellitus, 13 with impaired glucose tolerance [I GT], and 18 normal individuals). The 3 groups were well matched for gender, age, and body mass index (BMI). When adjusted for the BMI and gender, a st atistically significant gender-related difference in mean plasma leptin was observed across the 3 glucose tolerance subgroups (P < .03 by analysis of covariance [ANCOVA]). More specifically, plasma leptin levels were, on aver age, 44% lower in women with diabetes or IGT versus normal women (P < .02). No such between-group difference was observed in the men. In univariate an alysis in the same female subgroup, plasma leptin correlated positively wit h fasting insulin (r(s) = +.43, P < .06) and negatively with 2-hour post-75 -g glucose load plasma glucose concentration (r(s) = -.54, P < .02). In a m ultiple regression model controlling for the BMI in the female subgroup, ci rculating insulin and glucose concentrations 2 hours after the 75-g glucose load were good predictors of fasting plasma leptin (r = +.38, P = .02 and r = -.70, P < .001, respectively). Leptin levels in women appear to be infl uenced independently and to an important degree by ambient plasma glucose a nd plasma insulin concentrations. These findings suggest that the synthesis of leptin by adipose tissue is more susceptible to in vivo regulation by i nsulin and glucose in women than in men. Plasma leptin concentrations were also lower in women with IGT or type 2 diabetes versus normal women, sugges ting that fasting and/or postprandial hyperglycemia interferes with the sti mulatory effect of plasma insulin on the synthesis of leptin by adipose tis sue in women only. Copyright (C) 2000 by W.B. Saunders Company.