Aldosterone, Renin, and Diabetes Mellitus in African Americans: The Jackson Heart Study
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Joshua J Joseph1, Justin B Echouffo-Tcheugui1, Rita R Kalyani1
1Division of Endocrinology, Diabetes, and Metabolism (J.J.J., R.R.K., H.-C.Y., G.S.W., S.H.G.), Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; Division of Endocrinology, Diabetes, and Hypertension (J.B.E.-T.), Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts 02115; Rollins School of Public Health (J.B.E.-T.), Emory University, Atlanta, Georgia 30322; Division of Public Health Sciences (A.G.B., V.S.E., R.C.), Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157; Department of Medicine (M.S., A.C.), University of Mississippi Medical Center, Jackson, Mississippi 39216; and Department of Medicine (W.-C.W.), Warren Alpert Medical School of Brown University, Providence, Rhode Island 02903.
Context:
Previous research has suggested that activation of the renin-angiotensin-aldosterone system may promote insulin resistance and β-cell dysfunction, but the association with incident diabetes in African Americans is unknown.
Objective:
We examined the association of aldosterone and renin with insulin resistance, β-cell function, and incident diabetes in a large African American cohort.
Design:
The Jackson Heart Study is a prospective study of the development and progression of cardiovascular disease in African Americans.
Setting:
Participants were recruited from the tricounty area of metropolitan Jackson, Mississippi.
Participants:
A total of 5301 African American adults, aged 21–94 years, were assessed at baseline and through 12 years of follow-up. Data on aldosterone, renin, and risk factors were collected at baseline (2000–2004). Diabetes (fasting glucose ≥ 126 mg/dL, physician diagnosis, use of diabetes drugs, or glycated hemoglobin ≥ 6.5%) was assessed at baseline and through 12 years of follow-up. Participants were excluded for missing data on baseline covariates or diabetes follow-up. Cox regression was used to estimate hazard ratios (HR) for incident diabetes using sequential modeling adjusting for age, sex, education, occupation, systolic blood pressure, current smoking, physical activity, dietary intake, and body mass index.
Exposures:
Aldosterone, renin, and diabetes risk factors were measured.
Outcome:
Outcomes included the homeostatic model assessment of insulin resistance (HOMA-IR) and incident diabetes.
Results:
Among 3234 participants over a median of 8.0 years of follow-up, there were 554 cases of incident diabetes. Every 1% increase in log-transformed aldosterone was associated with a 0.18% higher log-transformed HOMA-IR in cross-sectional analyses of nondiabetic participants (P < .001). Log-transformed aldosterone and renin levels in the fifth vs first quintile were associated with a 78% (HR 1.78, 95% confidence interval 1.35–2.34) and 35% (HR 1.35, 95% confidence interval 1.06–1.72) increase in diabetes risk, respectively, in fully adjusted models.
Conclusions:
Activation of the renin-angiotensin-aldosterone system may play a significant role in the development of insulin resistance and diabetes in African Americans.