Aldosterone excess impairs first phase insulin secretion in primary aldosteronism

J Clin Endocrinol Metab. 2013 Jun;98(6):2513-20. doi: 10.1210/jc.2012-3934. Epub 2013 Mar 28.

Abstract

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 β-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. A normotensive 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] μU/mL, P = .031) and lower in comparison to essential hypertension without reaching statistical significance (53.2 [30.8; 73.3] μU/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] μU/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 β-cell function in patients with PA. After adrenalectomy, glucose-induced first-phase insulin secretion improves significantly in the patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aldosterone / physiology*
  • Blood Glucose / analysis
  • Female
  • Humans
  • Hyperaldosteronism / metabolism*
  • Hypertension / metabolism
  • Insulin / metabolism*
  • Insulin Secretion
  • Insulin-Secreting Cells / physiology
  • Male
  • Middle Aged
  • Prospective Studies

Substances

  • Blood Glucose
  • Insulin
  • Aldosterone