Aldosterone Excess Impairs First Phase Insulin Secretion in Primary Aldosteronism

Context: Primary aldosteronism (PA) represents the most frequent cause of secondary arterial hypertension. Conflicting data have been published regarding the effect of aldosterone excess on glucose metabolism. Objective: Our aim was to analyze insulin sensitivity and beta-cell function in a cohort of PA patients. Prospective follow-up investigations were performed in a subgroup of patients before and after adrenalectomy to assess the metabolic outcome. Design: Oral glucose tolerance test, combined intravenous glucose tolerance test, hyperinsulinemic-euglycemic glucose clamp test, and arginine test were carried out after a 12-hour fasting period. Patients: Twenty-two consecutive patients with both unilateral aldosterone-producing adenoma and bilateral idiopathic adrenal hyperplasia were recruited through the Munich center of the German Conn's Registry. The control group of patients with essential hypertension (n = 11) of corresponding age and body mass index was recruited from our hypertension unit. Anormotensive cohort (n = 11) served as a further control group. Results: At baseline, first-phase insulin reaction in intravenous glucose tolerance test was significantly reduced in patients with PA as compared to normal controls(36.0 [24.0; 58.7] vs 90.1 [52.6; 143.8] mu U/mL, P = .031) and lower in comparison to essential hypertension without reaching statistical significance (53.2 [30.8; 73.3] mu U/mL, P = .123). The study was repeated 6 months after unilateral adrenalectomy in 9 consecutive patients with aldosterone-producing adenoma. At this time point, blood pressure had been normalized in most of the patients while body mass index remained unchanged (26.9 [25.5; 37.6] vs 27.5 [25.1; 35.6] kg/m(2), P = .401). First-phase insulin reaction in response to glucose significantly increased at follow-up (from 36.0 [25.5; 58.7] to 48.5 [40.4; 95.2] mu U/mL, P = .038, n = 9). In contrast, insulin sensitivity and response to iv arginine did not differ before and after adrenalectomy. Conclusion: Aldosterone excess has a direct negative effect on beta-cell function in patients with PA. After adrenalectomy, glucose-induced first-phase insulin secretion improves significantly in the patients.