Abstract

We have investigated the relationships between plasma interleukin-6 (IL-6) levels and insulin sensitivity and insulin secretion in a cohort of Italian-Caucasian glucose-tolerant subjects. Insulin sensitivity was assessed by euglycemic-hyperinsulinemic clamp, and first-phase insulin secretion was measured by intravenous glucose tolerance test. Fasting plasma IL-6 concentration was negatively correlated with the rate of insulin-stimulated glucose disposal (M) (P = 0.001). The correlation remained statistically significant, while attenuated, after adjusting for sex, age, and BMI (P < 0.03); after an additional adjustment for free fatty acids (FFAs), a further attenuation was observed, but statistical significance was maintained (P < 0.044). Fasting plasma IL-6 concentration was positively correlated with first-phase insulin secretion assessed as acute insulin response (AIR) (P = 0.001). The correlation remained significant after adjusting for sex, age, and BMI (P = 0.003). To estimate the independent contribution of plasma IL-6 levels to AIR, we carried out forward stepwise linear regression analysis in a model that included sex, age, BMI, waist-to-hip ratio, FFAs, and insulin-stimulated glucose disposal. Only insulin sensitivity and plasma IL-6 concentration were independently associated with AIR, accounting, respectively, for 19.0 and 5.2% of its variation. These data indicate that IL-6 is associated in a reciprocal manner with the two pathophysiological components of type 2 diabetes, i.e., insulin resistance and insulin secretion.

Highlights

  • We have investigated the relationships between plasma interleukin-6 (IL-6) levels and insulin sensitivity and insulin secretion in a cohort of Italian-Caucasian glucosetolerant subjects

  • Fasting plasma IL-6 concentration was positively correlated with BMI, fasting and 2-h postload insulin concentrations, and fasting free fatty acid (FFA) levels (Table 2)

  • Adjustment for FFAs in addition to sex, age, and BMI resulted in further attenuation of the significant correlation between plasma IL-6 concentration and insulin-stimulated glucose disposal (P Ͻ 0.044)

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Summary

Introduction

We have investigated the relationships between plasma interleukin-6 (IL-6) levels and insulin sensitivity and insulin secretion in a cohort of Italian-Caucasian glucosetolerant subjects. Fasting plasma IL-6 concentration was positively correlated with first-phase insulin secretion assessed as acute insulin response (AIR) (P ‫ ؍‬0.001). To estimate the independent contribution of plasma IL-6 levels to AIR, we carried out forward stepwise linear regression analysis in a model that included sex, age, BMI, waist-to-hip ratio, FFAs, and insulin-stimulated glucose disposal. Several studies have shown that proinflammatory cytokines and acute-phase reactants are correlated with clinical features of the metabolic syndrome, including measures of insulin resistance/plasma insulin concentration, BMI/waist circumference, and circulating triglyceride and HDL cholesterol concentration (2,4 – 6). Circulating IL-6 levels have been reported to be elevated in subjects with type 2 diabetes [1] and to correlate with direct and indirect measures of insulin resistance (6,9 –11). After 12 h fasting, all subjects underwent anthropometrical evaluation, and a 75-g oral glucose tolerance test was performed with 0, 30, 60, 90, and 120 min sampling

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