Increased Aldosterone Linked to Type 2 Diabetes

Nancy A. Melville

September 07, 2018

Increased levels of aldosterone are independently associated with a greater risk of type 2 diabetes, with the effects particularly notable in certain ethnic groups including African Americans and particularly Chinese Americans, who are up to 10 times more likely to develop diabetes if their aldosterone levels are high, new research indicates.

Aldosterone, a hormone produced by the adrenal glands, is known to be linked to hypertension and has recently been associated with impaired insulin secretion and sensitivity.

"In this contemporary, prospective study of multiethnic adults without type 2 diabetes, aldosterone was positively associated with fasting plasma glucose, insulin resistance, and risk of incident type 2 diabetes over 10.5 years," say Joshua J. Joseph, MD, of Ohio State Wexner Medical Center, Columbus, and colleagues in their article, published online September 4 in the Journal of the American Heart Association.

"We know there's a relationship between aldosterone and type 2 diabetes," Joseph said in a press statement, adding that he and his colleagues plan to continue the research in a federally funded clinical trial to further explore the role of aldosterone in glucose metabolism. Patient enrollment is expected to begin next year.

The ultimate goal is to discover whether targeting aldosterone in any way, for example via the renin-angiotensin-aldosterone system (RAAS), can help prevent development of type 2 diabetes, and if this is the case, to determine thresholds that will guide clinical care and the best medication for treatment, they explain.

Increased Aldosterone Linked to Increased Diabetes Risk in MESA

To better understand the role of aldosterone in type 2 diabetes, Joseph and coauthors evaluated prospective data on 1570 adults participating in the Multi-Ethnic Study of Atherosclerosis (MESA).

The participants were aged 45 to 84 years, and 44% were white, 13% were Chinese American, 19% were black,  and 24% were Hispanic American. They had no evidence of clinical cardiovascular disease at baseline. Over a 10.5-year follow-up, there were 116 cases of incident diabetes, defined as fasting plasma glucose ≥ 126 mg/dL or use of antidiabetic medication at follow‐up.

Overall, a 100% increase in aldosterone was associated with a 2.6-mg/dL higher fasting plasma glucose, in addition to increased abnormalities in measures of glucose homeostasis (P < .01).

Whereas each standard deviation in log-aldosterone was associated with a 44% increased risk of diabetes in the group overall (P < .01), the increase was 49% in African Americans and as much as 142% in Chinese Americans (P < .01).

The associations persisted after adjusting for a variety of key type 2 diabetes risk factors including age, socioeconomic status, race/ethnicity, physical activity, waist circumference, adipokines (leptin and adiponectin), and inflammation (high-sensitivity C-reactive protein, interleukin‐6, tumor necrosis factor alpha), the authors say.

In addition, the type 2 diabetes risk was increased regardless of whether participants had an unsuppressed or suppressed renin phenotype.

"[Those renin phenotype results] indicate that individuals with physiologically and autonomously higher aldosterone are both at higher risk of type 2 diabetes," they comment.

Further analyses showed dose-dependent associations between aldosterone levels and incident type 2 diabetes in Chinese Americans and blacks, but not Hispanic Americans or whites, suggesting differences in physiology as a potential factor.

They speculate on possible mechanisms that could explain the increased association seen particularly among Chinese Americans, including salt sensitivity, production of aldosterone, and receptor binding and post-receptor signal transduction in response to aldosterone.

Notable study limitations include the fact that aldosterone was measured at just one point in time, preventing the assessment of changes in the measure in relation to glucose metabolism. In addition, measures of 24-hour urinary sodium were not available, preventing assessment of dietary salt intake.

Nevertheless, with the potentially important clinical implication of targeting aldosterone in preventing type 2 diabetes, the need to better understand the mechanisms of the association is pressing, they conclude.

"Further research to elucidate mechanisms for the racial/ethnic differences in the association of aldosterone with incident type 2 diabetes is of preeminent importance given the potential to lower risk of type 2 diabetes through targeted modulation of the RAAS."

The study received grant support from the National Heart, Lung, and Blood Institute and National Institute of Diabetes and Digestive and Kidney Diseases. The authors have reported no relevant financial relationships.

J Am Heart Assoc. Published online September 4, 2018. Full text

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