Abnormal Cation Exchange in Insulin-Resistant Patients with Essential Hypertension : Cardiovascular Topics

ABSTRACT

Objectives: To identify important factors that may contribute to abnormal glucose tolerance in elderly patients with treated hypertension with primary reference to changes in the following parameters calculated insulin resistance; endogenous insulin processing and secretion; platelet cation concentration and membrane ATPase activity. Design: Thirty-nine patients receiving antihypertensive therapy (including low-dose thiazide treatment) were compared to 13 normotensive; normoglycaemic control subjects. Total platelet cation concentration and membrane ATPase activity were measured and; following a 75-g oral glucose test; serum insulin; proinsulin and 31-32 des-proinsulin responses were measured in prospectively defined hypertensive patients with normal glucose tolerance (NG); impaired glucose tolerance (iGT) and diabetes mellitus (DM). Results: of the total patient cohort; seven patients manifested newly diagnosed DM; 18 had iGT and 14 NG. Among the three groups; no difference in duration of drug use (thiazides and beta-blockers) was noted; BMi and waist-to-hip ratio increased progressively from NG to iGT to overt DM. Compared to NG patients; serum insulin responses were significantly greater in the iGT (all time points) and DM (two-hour measurements) subjects. Proinsulin and 31-32 des-proinsulin serum responses were likewise significantly higher in the iGT and DM groups. The derived measure of insulin resistance in the hypertensive patients showed a significant increase in the progression from NG to iGT and DM. Mean total platelet potassium concentration was reduced in the DM compared to the iGT and the control groups; while platelet sodium; calcium and magnesium concentrations showed no Significant differences. Platelet membrane magnesium ATPase activity was significantly higher in the normotensive control versus the hypertensive group. Sodium; potassium and calcium ATPase activity showed no significant differences among the subgroups. Conclusion: our findings support the strong link between essential hypertension; insulin resistance / hyperinsulinaemia and regional adiposity. Beta-cell dysfunction (hypersecretion and abnormal insulin processing) is manifest in the progression from normality to overt diabetes. The use of antihypertensive therapy (low-dose thiazides and cardioselective beta-blockers) possibly added diabetogenic effect(s). The reduction in platelet total potassium concentration paralleled the diabetic state while a reduced membrane magnesium ATPase activity correlated with the hypertensive state