Glucose Metabolism in Primary Aldosteronism

Abstract

In recent years, an increasing number of studies have revealed deleterious effects of aldosterone via the mineralocorticoid receptor (MR). Especially in patients with primary aldosteronism (PA) a significant higher estimated risk of developing cardiovascular comorbidities and comortalities compared to essential hypertensives was reported. As diabetes mellitus and the metabolic syndrome are one of the major contributors to cardiovascular morbidity and mortality their connection to aldosterone excess became a focus of research in PA patients. Several studies assessed the effect of PA on glucose metabolism, the prevalence of diabetes mellitus, and the effect of PA treatment on both revealing different results. Therefore, we performed an extensive literature research. This review focuses on the current knowledge of the connection between aldosterone excess, glucose homeostasis, and diabetes mellitus in patients with PA. We have highlighted this topic from a pro and contra perspective followed by a summarizing concluding remark. Additionally, we have briefly reviewed the data on possible underlying mechanisms and indicated future considerations on the possible impact of cortisol co-secretion in PA.

Effects of Primary Aldosteronism and Different Therapeutic Modalities on Glucose Metabolism

“…Hypokalemia was associated with lower insulin secretion from pancreatic β-cells in an in vitro study; therefore, the presence of hypokalemia in PA might confound investigations of the link between PA and glucose status [11,16,39]. Therefore, we also separately analyzed PA patients according to hypokalemia status and adjusted for hypokalemia.…”

“…Only few data from human studies are available regarding the molecular mechanisms underlying the impairment in glucose metabolism in PA [26]. However, many studies conducted in animal and cell models suggest that aldosterone impairs glucose metabolism at several levels, including insulin secretion, hepatic glucose production and uptake, and glucose diffusion and uptake into insulin-sensitive tissues [5][6][7][8][9][10][11][12][13][14]. In the present study, the subgroup analysis (comprising~28% of the study subjects) showed that HOMA-β was lower in PA patients than in matched controls.…”

“…Data from studies in animal and cell models, aldosterone impairs insulin secretion and increases IR through MR-dependent and MR-independent mechanism [5][6][7][8][9][10][11][12][13][14], but regarding comparisons of the effects of ADX and MRA therapy on glucose metabolism in PA have only sparsely been studied [21,24,29,30]. One study showing no difference in decreased IR between ADX and MRA therapy [21] was in agreement with data from in vitro and animal studies showing MRA reduced IR via inhibited expression of pro-inflammatory factors and promoted expression of insulin-sensitizing factors such as peroxisome proliferator-activated receptor-γ and adiponectin in adipocytes [7] and via reduced inflammatory cytokines in the liver [13].…”

“…Although one study showed no differences in decreased IR between the treatment modality (ADX vs. MRA therapy) [21], other clinical studies showed improved glucose metabolism in APA patients after ADX, but not in BAH patients after MRA therapy [24,29,30] and increased insulin secretion in APA patients after ADX [23,31]. However, previous clinical studies comparing the effects of ADX and MRA therapy used only small numbers of patients (N = 9-61), and therefore definitive conclusions cannot be drawn from these [11].…”

“…This suggests that there are effects of aldosterone excess, independent of blood pressure (BP), on multiple organ systems [4]. Many studies conducted in animal and cell models have suggested that aldosterone excess can also impair glucose metabolism by impaired insulin secretion and by increased insulin resistance (IR) at several levels; hepatic glucose production and uptake, and glucose diffusion and uptake into insulin-sensitive tissues through a mineralocorticoid 2 of 14 receptor (MR)-dependent and MR-independent mechanism [5][6][7][8][9][10][11][12][13][14]. Furthermore, the American Diabetes Association lists APA-induced hypokalemia as a secondary cause of type 2 diabetes mellitus (DM) [15].…”