Biomarkers of subclinical inflammation and increases in glycaemia, insulin resistance and beta-cell function in non-diabetic individuals: the Whitehall II study

Objective: Higher systemic levels of proinflammatory biomarkers and low adiponectin are associated with increased risk for type 2 diabetes, but their associations with changes in glycaemic deterioration before onset of diabetes are poorly understood. We aimed to study whether inflammation-related biomarkers associated with 5-year changes in glucose and insulin, HbA1c, insulin sensitivity and beta-cell function before the diagnosis of type 2 diabetes and whether these associations may be bidirectional. Design and Methods: We used multiple repeat measures (17,891 person-examinations from 7,683 non-diabetic participants) from the Whitehall II study to assess whether circulating high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), IL-1 receptor antagonist (IL-1Ra) and adiponectin associated with subsequent changes in glycaemia, insulin, insulin resistance and beta-cell function (based on oral glucose tolerance tests). We examined bidirectionality by testing if parameters of glucose metabolism at baseline associated with changes in inflammation-related biomarkers. Results: Higher hsCRP and IL-6 were associated with increases in fasting insulin, insulin resistance and, for IL-6, with beta-cell function after adjustment for confounders. Higher adiponectin associated with decreases in fasting glucose, HbA1c, fasting insulin, insulin resistance and beta-cell function. The reverse approach showed that 2-hour glucose and insulin sensitivity associated in opposite directions with changes in IL-1Ra. Fasting insulin and insulin resistance showed inverse associations with changes in adiponectin. Conclusions: Subclinical inflammation associated with development of increased glycaemia, insulin resistance and beta-cell function in non-diabetic individuals. These findings are consistent with the hypothesis that inflammation-related processes may increase insulin resistance and lead to a compensatory upregulation of beta-cell function