[The relationship between serum leptin, proinsulin, true insulin levels and insulin resistance in non-diabetic...

Leptin is involved in the regulation of body weight and metabolism. Previous data have suggested that leptin levels are related to insulin resistance and in a few reports with impaired insulin secretion. Some even revealed the existence of adipoinsular axis. However, little is known of these relations in Chinese population. With the availability of measurements of true insulin (TI), proinsulin (PI) and leptin, we examined the possible correlation of leptin with TI, PI and with insulin resistance (the HOMA model) in non-diabetic subjects of north China. We also evaluated whether leptin levels were associated with impaired insulin secretion, as evaluated by the fasting PI/TI ratio.

902 non-diabetic subjects (670 with normal and 232 impaired glucose tolerance, aged 30 - 80 y) from a population of Beijing residents who underwent a diabetes survey in 2000 were studied. Fasting serum leptin, PI and TI levels were detected by sensitive and specific enzyme-linked immunosorbent assays (ELISA) which were all developed in our laboratory.

Serum leptin values were higher in women. Correlation analysis showed that leptin levels were significantly correlated with fasting TI, PI and insulin resistance (HOMA-IR) (in men, n = 794, r = 0.345, 0.236 and 0.364 respectively; in women, n = 110, r = 0.574, 0.375 and 0.576 respectively, P < 0.001), but not with PI/TI ratio (r = -0.09, P < 0.01) in both sex. After adjustment for age, body mass index (BMI) and waist-to-hip ratio (WHR), leptin levels remained significantly correlated with TI, PI and HOMA-IR, although the magnitude of the association was considerably attenuated.

TI and PI levels were positively related to leptin levels independent of obesity and body fat distribution. Thus, subjects with increased insulin levels and/or insulin resistance may be relatively resistant to the effects of leptin, suggesting a dysfunction of leptin-insulin axis. However, leptin levels are not significantly associated with the fasting PI/TI ratio suggesting that leptin levels are not associated with an impairment in insulin secretion. The role of association between hyperinsulinemia/insulin resistance and hyperleptinemia/leptin resistance in the pathogenesis of insulin resistance-related diseases needs further study.