Plasma Aldosterone Levels and Development of Insulin Resistance

Abstract

Abstract-Aldosterone plays a role in hypertension, and hypertension is prevalent in patients with insulin resistance.Cross-sectional studies have reported that plasma aldosterone levels are higher in patients with insulin resistance. However, it is not known whether plasma aldosterone levels predict the development of insulin resistance. Subjects of the present study were 1235 local residents (490 men and 745 women) who participated in health screenings in Japan in 1999. Plasma aldosterone levels were measured by radioimmunoassay. We investigated the cross-sectional relationship between plasma aldosterone levels and insulin resistance (homeostasis model assessment index Ն1.73 according to the diagnostic criteria used in Japan) in 1088 nondiabetic participants. At the 10-year follow-up, 141 subjects had died, and 260 subjects refused re-examination. We performed a prospective analysis of 564 subjects to predict incident insulin resistance. We found a significant (PϽ0.001) cross-sectional relationship between plasma aldosterone and homeostasis model assessment index at baseline. In the prospective analysis, a significantly higher (PϽ0.05) relative risk ( he most important physiological role of aldosterone is to control water homeostasis and electrolytes balance. High levels of adrenal aldosterone secretion cause hypertension, that is, primary aldosteronism, a well-known form of secondary hypertension. Moreover, high plasma aldosterone levels predict the development of hypertension. 1 In view of the fact that aldosterone is a mineral corticosteroid, the association of aldosterone and hypertension is not doubted. Recently, the association between aldosterone and obesity or insulin resistance has attracted much attention. Experimental evidence suggests an interaction between aldosterone and insulin. 2 Aldosterone induces hypokalemia, which may modulate insulin secretion, has direct effects on insulin receptor function, 3,4 causes pancreatic ␤-cell dysfunction or even apoptosis, 5 interferes with insulin signaling pathways, 6 and decreases insulin sensitivity in human adipocytes in vitro. 7 Moreover, aldosterone reduces the expression of insulinsensitizing factors, such as adiponectin and peroxisome proliferator-activated receptor-␥, in obese, diabetic mice. 8 In addition to the above-mentioned in vitro and animal studies, several clinical studies reported an association between plasma aldosterone levels and insulin resistance. Plasma aldosterone levels are elevated in hypertensive obese subjects. 9 Cross-sectional studies have shown an association between plasma aldosterone levels and insulin resistance in hypertensive and normotensive subjects. 10,11 Moreover, insulin resistance was restored by surgical intervention or mineralocorticoid receptor blocker in primary hyperaldosteronism. 12 However, contradictory results were reported by other investigators showing no difference of glucose metabolism in a relatively small number of subjects with primary hyperaldosteronism and essential hypertension 13 and showing no cha...

High-salt intake induced visceral adipose tissue hypoxia and its association with circulating monocyte subsets in humans

“…The RAAS, especially aldosterone, has been increasingly recognized as a major player in linking salt intake and metabolic syndrome (13). Increased aldosterone level is independently associated with the development of insulin resistance in general population (29). Our data confirmed previous finding that short-term high-salt intake can suppress systemic RAAS, whereas switching to a low-salt diet would induce a rebound activation of RAAS, leading to impaired insulin metabolic signaling (13,30).…”

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

“…In a large population of individuals of Chinese and Japanese ancestry, CYP11B2 polymorphisms (Arg‐173 and T‐344C) were associated with higher FPG levels, higher 2‐hour post load glucose, impaired fasting glucose and type 2 diabetes mellitus,25 which is consistent with our findings of a high risk of type 2 diabetes mellitus in Chinese Americans with higher levels of aldosterone. Additionally, a prospective Japanese cohort study with 10 years of follow‐up demonstrated that plasma aldosterone levels predict the development of insulin resistance,26 suggesting our findings might extend to individuals with ancestry from the continent of Asia. Thus, genetic differences in production or response to aldosterone may be responsible for racial/ethnic differences.…”

Angiotensin 1–7 Is a Negative Modulator of Aldosterone Secretion In Vitro and In Vivo

“…Because aldosterone excess per-se has been linked to multiple potential unfavorable sequels, such as the evolution of hypertension, 25 cardiac and vascular fibrosis, 26,27 insulin resistance, 28 and worse prognosis after myocardial infarction, 29 the present report should instigate further studies of whether/how this previously unrecognized inhibitor of aldosterone secretion can be used under conditions in which high circulating aldosterone is a likely contributor to disease.…”