Circulating Interleukin‐6 in Relation to Adiposity, Insulin Action, and Insulin Secretion

OBJECTIVE: Plasma concentrations of interleukin-6 (IL-6), a proinflammatory cytokine produced and released in part by adipose tissue, are elevated in people with obesity and type 2 diabetes. Because recent studies suggest that markers of inflammation predict the development of type 2 diabetes, we examined whether circulating plasma IL-6 concentrations were related to direct measures of insulin resistance and insulin secretory dysfunction in Pima Indians, a population with high rates of obesity and type 2 diabetes. RESEARCH METHODS AND PROCEDURES: Fasting plasma IL-6 concentrations (enzyme-linked immunosorbent assay), body composition (DXA), insulin action (M; hyperinsulinemic euglycemic clamp), and acute insulin secretory responses to glucose (25 g intravenous glucose tolerance test) were measured in 58 Pima Indians without diabetes (24 women, 34 men). RESULTS: Fasting plasma IL-6 concentrations were positively correlated with percentage of body fat (r = 0.26, p = 0.049) and negatively correlated with M (r = -0.28, p = 0.031), but were not related to acute insulin response (r = 0.13, p = 0.339). After adjusting for percentage of body fat, plasma IL-6 was not related to M (partial r = -0.23, p = 0.089). DISCUSSION: Fasting plasma IL-6 concentrations are positively related to adiposity and negatively related to insulin action in Pima Indians. The relationship between IL-6 and insulin action seems to be mediated through adiposity.