Newly identified genetic locus influencing fasting plasma glucose levels in people with Type 2 diabetes: the Edinburgh Type 2 Diabetes Study (ET2DS)

Context: Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis may underlie the metabolic syndrome, but whether circulating cortisol levels predict cardiovascular end points is less clear. People with type 2 diabetes are at increased cardiovascular disease risk and thus are suitable to study associations of plasma cortisol with cardiovascular risk.Objective: We aimed to assess whether altered HPA axis activity was associated with features of the metabolic syndrome and ischemic heart disease in people with type 2 diabetes.Design and setting: We conducted a cross-sectional cohort study in the general community, including 919 men and women aged 67.9 (4.2) yr with type 2 diabetes (the Edinburgh Type 2 Diabetes Study).Intervention: We measured fasting morning plasma cortisol.Main outcome measurement: Associations between cortisol levels, features of the metabolic syndrome, obesity, and ischemic heart disease were determined.Results: Elevated plasma cortisol levels were associated with raised fasting glucose and total cholesterol levels (P < 0.001). These findings remained significant after adjustment for potential confounding factors (P < 0.001). Elevated cortisol levels were associated with prevalent ischemic heart disease (>800 vs. <600 nmol/liter; odds ratio, 1.58; P = 0.02). This association remained significant after adjustment for duration and control of diabetes and other cardiovascular risk factors (P = 0.03).Conclusions: The previously described associations between HPA axis activation and features of the metabolic syndrome are present among people with type 2 diabetes. Elevated plasma cortisol is also associated with a greater prevalence of ischemic heart disease, independent of conventional risk factors. Understanding the role of cortisol in the pathogenesis of ischemic heart disease merits further exploration.