Renin‐Angiotensin‐Aldosterone System, Glucose Metabolism and Incident Type 2 Diabetes Mellitus: MESA

BACKGROUND: Mechanistic studies suggest that aldosterone impairs glucose metabolism. We investigated the cross‐sectional associations of aldosterone and plasma renin activity with fasting plasma glucose, insulin resistance (IR), β‐cell function, and longitudinal association with incident diabetes mellitus among adults in MESA (the multiethnic study of atherosclerosis) prospective cohort study. METHODS AND RESULTS: Homeostatic model assessment of IR (HOMA2‐IR) and HOMA2‐β were used to estimate IR and β‐cell function, respectively. Incident diabetes mellitus was defined as fasting plasma glucose ≥126 mg/dL or anti‐diabetic medication use at follow‐up. Linear regression was used to examine cross‐sectional associations of aldosterone with fasting plasma glucose, HOMA2‐IR and HOMA2‐β; Cox regression was used to estimate hazard ratios (HR) for incident diabetes mellitus with multivariable adjustment. There were 116 cases of incident diabetes mellitus over 10.5 years among 1570 adults (44% non‐Hispanic white, 13% Chinese American, 19% Black, 24% Hispanic American, mean age 64±10 years, 51% female). A 100% increase in log‐aldosterone was associated with a 2.6 mg/dL higher fasting plasma glucose, 15% higher HOMA2‐IR and 6% higher HOMA2‐β (P<0.01). A 1‐SD increase in log‐aldosterone was associated with a 44% higher risk of incident diabetes mellitus (P<0.01) with the greatest increase of 142% (P<0.01) observed in Chinese Americans (P for interaction=0.09 versus other ethnicities). Similar cross‐sectional findings for log‐plasma renin activity existed, but log‐plasma renin activity was not associated with incident diabetes mellitus after full adjustment. CONCLUSIONS: Aldosterone is associated with glucose homeostasis and diabetes mellitus risk with graded associations among Chinese Americans and blacks, suggesting that pleiotropic effects of aldosterone may represent a modifiable mechanism in diabetes mellitus pathogenesis with potential racial/ethnic variation.