Aldosterone Is Associated with Higher Glucose, Insulin Resistance and Incident Diabetes Among Community Dwelling Adults: The Multi-Ethnic Study of Atherosclerosis

Presentation Number: OR42-2
Date of Presentation: April 3rd, 2017

Joshua J. Joseph*1, Justin B. Echouffo Tcheugui2, Valery S. Effoe3, Willa Ann Hsueh1, Matthew Allison4 and Sherita H. Golden5
1The Ohio State University Wexner Medical Center, Columbus, OH, 2Brigham and Women's Hospital, 3Morehouse School of Medicine, 4University of California, San Diego, 5Johns Hopkins School of Medicine, Baltimore, MD

Abstract

Introduction:

Mechanistic studies suggest that aldosterone excess may impair insulin secretion, insulin action, or both. There is limited human data on the role of aldosterone in the development of type 2 diabetes mellitus (diabetes). The role of aldosterone in the pathogenesis of diabetes has not been evaluated in a US multi-ethnic sample of community dwelling adults. We hypothesized that aldosterone would be positively associated with fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR) and incident diabetes in The Multi-Ethnic Study of Atherosclerosis (MESA).

Methods:

Using data from the MESA, we examined: (1) the cross-sectional associations of aldosterone with FPG and HOMA-IR and (2) the longitudinal association of aldosterone with incident diabetes among individuals without prevalent diabetes. Diabetes was defined based on FPG (≥ 126 mg/dl) or hypoglycemic medication use. After adjustment for age, sex, study site, race/ethnicity, education, alcohol consumption, physical activity, estimated glomerular filtration rate, systolic blood pressure (BP), body mass index (BMI), angiotensin converting enzyme inhibitors and angiotensin receptor blockers, linear regression was used to examine the association of aldosterone with both FPG and HOMA-IR, while Cox regression was used to estimate the adjusted hazard ratio (HR) for incident diabetes. Aldosterone was log-transformed for analyses due to a skewed distribution.

Results:

Among 1,547 adults (44% non-Hispanic white, 13% Chinese, 19% Black, 24% Hispanic, mean age 64 ± 10 years, 51% female), 115 incident diabetes cases occurred over 9.5 years (7.8 cases/1,000 person-years). Participants in higher tertiles of log-aldosterone had higher FPG, HOMA-IR and interleukin-6 (All P<0.05), compared to participants in the lowest tertile. In cross-sectional analyses, every 1% increase in log-transformed aldosterone was associated with a 0.024 mg/dl higher FPG and 0.18% higher HOMA-IR (both p<0.001). Moreover, a 1-SD increase in log-aldosterone was associated with a 34% increase in risk for incident diabetes (HR 1.34, 95%CI: 1.10-1.62) after adjustment. Additional adjustment for inflammatory markers (hs- CRP, IL-6 and TNF-α) and adipokines (adiponectin and leptin) modestly attenuated the association (HR 1.26 95% CI: 1.04-1.54). Compared to tertile 1 of aldosterone, the HRs for tertiles 2 and 3 were 2.87 (95% CI: 1.70-4.84) and 2.65 (95% CI: 1.55-4.52), respectively after standard adjustment. We found no evidence for interactions between the association of log-aldosterone with incident diabetes by age, sex or race/ethnicity.

Conclusion: Aldosterone is significantly associated with measures of glucose homeostasis and diabetes risk in a multi-ethnic US cohort of individuals without diabetes, suggesting pleiotropic effects of aldosterone may be relevant to the pathogenesis of diabetes.

 

Nothing to Disclose: JJJ, JBE, VSE, WAH, MA, SHG