Abnormal cation exchange in insulin-resistant patients with essential hypertension.

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.

Chronic laxative abusers with pseudo-idiopathic oedema and autonomous pseudo-Bartter's syndrome. A spectrum of metabolic madness, or new lights on an old disease?

The numerous metabolic abnormalities encountered in chronic purgative abusers were investigated and the new concept of autonomous pseudo-Bartter's syndrome documented. Detailed metabolic screening tests were performed in 9 women aged 17-54 years. Two patients underwent further studies, including serum renin and aldosterone, blood volume, total body potassium, urinary chloride and prostaglandin determinations, and each underwent renal biopsy on admission and after 1 year free from laxative abuse. Clinical complications included confusion, convulsions, coma, skeletal muscle weakness with or without paralysis or rhabdomyolysis, cardiac failure, urinary tract infections and bone disease (osteomalacia, secondary hyperparathyroidism and osteoporosis). Hypokalaemia, hypomagnesaemia, hypocalcaemia and hypophosphataemia were frequent findings. Serum creatine kinase correlated inversely with the product of the potassium and serum phosphate (r = -0.86; P less than 0.03), suggesting that hypokalaemia and hypophosphataemia act synergistically to produce muscle damage. After laxative withdrawal, oedema and weight gain, followed by diuresis, ensued in 7 patients. In the other 2, ongoing chloruresis, kaliuresis, hyper-reninaemia and raised urinary prostaglandin secretion persisted. Renal biopsies in these 2 patients showed the features of juxtaglomerular apparatus hyperplasia as well as medullary interstitial cell hyperplasia. In conclusion, pseudo-Bartter's syndrome was documented in 9 chronic laxative abusers. Because patients often indulged in more than one aberrant habit, e.g. laxative and/or diuretic abuse or bulimia, the clinical syndrome produced a myriad of confounding metabolic derangements, which we termed 'metabolic madness'. Laxative withdrawal was complicated by temporary pseudo-idiopathic oedema, which persisted in 2 patients. Further studies in these 2 women strongly supported the concept of 'autonomous pseudo-Bartter's syndrome'.(ABSTRACT TRUNCATED AT 250 WORDS)