Insulin action in primary hyperaldosteronism before and after surgical or pharmacological treatment

Abstract

The relationship between arterial hypertension and insu lin resistance has long been established. We used primary hyperal dosteronism as a model of the relationship between secondary hy pertension and insulin sensitivity. Our group consisted of 9 patients with arterial hypertension caused by primary hyperaldosteronism. Five of these patients with aldosterone producing adenoma were operated on and four patients with idiopathic hyperaldosteronism were treated with spironolactone. Hyperinsulinaemie euglycaemic clamp technique was performed before and at least 6 months fol lowing the treatment to evaluate the insulin action. Significantly lower glucose disposal rate (M), insulin sensitivity index (M/I) and decreased metabolic clearance rale of glucose (MCR (i ) were found in patients before treatment as compared to healthy controls. In both treated groups the blood pressure and plasma potassium con centrations returned to normal values, whereas plasma aldosterone levels were normalised only after surgical removal of the adenoma. Significantly improved insulin action (M/I: 30.2 ± 5.9 vs. 51.4 ± 12.2 umol.kg" '.min 1 per mU.l" 1 X 100, p = 0.017) was observed in patients after operation of aldosterone producing adenoma. In contrast, spironolactone treatment of patients with idiopathic hyp eraldosteronism did not significantly influence insulin action (M/I: 24.5 ± 7.3 vs. 18.7 ± 7.6 umol.kg-'.rnin-' per mU.l 1 x 100, p = 0.198). Since plasma aldosterone concentrations have been normal ised only in patients after removal of the adenoma whereas they remained increased in spironolactone treated group, we suppose that aldosterone itself could play a role in the development of im paired insulin action. Downloaded by: Collections and Technical Services Department. Copyrighted material. G. Sindelka et al., Insulin action in primary hyperaldosteronism Torlone E, Rambotti AM, Perriello G, Botta G, Santeusanio F, Brunetti P, Bolli GB: ACE-inhibition increases hepatic and extrahepatic sensitivity to insulin in patients with type 2 (non-insu lin-dependent) diabetes mellitus and arterial hypertension. Diabetologia 34: 119-125, 1991 Tylor SI: Lilly lecture: Molecular mechanisms of insulin resistance. Lessons from patients with mutations in the insulin-receptor gene. Diabetes 41: 1473-1490, 1992 Widimsky J, Skrha J, Sindelka G, Hilgertova J: Is insulin resistance in primary hyperaldosteronism modifiable by treatment? J Hypert 16, Suppl SI48, 1998 Yajnik CS, Naik SS, Bhat DS, Joshi VM, Shelgikar KM, Alberti KGMM, Hockaday TDR: The relationship between obesity, 25 plasma immunoreactive insulin concentration and blood pres sure in newly diagnosed Indian type 2 diabetic patients. Diab Med 10: 146-151, 1993 Zemel MB: Insulin resistance, obesity and hypertension: an over view.

Increased prevalence of diabetes mellitus and the metabolic syndrome in patients with primary aldosteronism of the German Conn's Registry

“…The largest study in the field (21), including 460 patients with PA and 1363 controls with essential hypertension reported no differences regarding proportions of hyperglycemia or fasting glucose levels. On the other hand, there is evidence that patients with PA have a disturbed glucose metabolism (13,16,18,19). Thirty PA patients had higher glucose, lower C-peptide levels and lower HOMA-bF index than 60 patients with essential hypertension (19).…”

“…However, the findings are inconsistent (12,13,14,15,16,18,19,21). Two smaller studies (nZ24 (14) and 63 subjects (15)) and one large study (nZ1823 subjects (21)) reported no association between PA and glucose metabolism (including insulin sensitivity index, HOMA, or quantitative insulin sensitivity check index (QUICKI).…”

“…Previous studies have described abnormalities in glucose homeostasis and metabolism in patients with PA (12,13,14,15,16,17,18,19,20,21,22); however, they often showed inconsistent results due to limitations in sample size, lacking of a matched control group, or nonstandardized diagnosis of PA. Nevertheless, there is growing evidence that aldosterone is involved in the pathogenesis of insulin resistance and MetS (23,24).…”

Aldosterone excess may inhibit insulin secretion: A comparative study on glucose metabolism pre- and post-adrenalectomy in patients with primary aldosteronism

“…Fischer et al showed that adrenalectomy for APA (n = 9) did not affect the index of insulin resistance, assessed using the insulin clamp method [7]. Two other studies reported that improvements in insulin sensitivity were observed in patients with APA after adrenalectomy, but not in patients with idiopathic adrenal hyperplasia treated with MR-antagonists [23,24]. The limited number of patients and the different study protocols used may explain the conflicting results.…”

Aldosterone and Obesity: Where to Look for the Key to Therapy?

“…Определенную роль в реализации данного со-стояния играет гипокалиемия, часто сопровождаю-щая гиперальдостеронизм. Подробный механизм этого влияния до конца не изучен, более того, он опровергается рядом авторов [45], которые наблю-дали прогрессирование инсулинорезистентности у пациентов с ПГА, несмотря на инфузию калия.…”