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)
Summary
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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