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J Intern Med Suppl. 1991;735:89-96.

Metabolic adverse effects of thiazide diuretics: the importance of normokalaemia.

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1
Department of Internal Medicine, Sahlgrenska Hospital, Göteborg, Sweden.

Abstract

It has been suggested that the failure of thiazide therapy, administered to treat high blood pressure, to prevent coronary heart disease is related to the metabolic adverse effects of these drugs. The almost consistent observation of reduced serum potassium and total body potassium associated with diuretics appears to be of clinical importance. It may cause not only an increased risk of cardiac arrhythmias but also impaired glucose tolerance and abnormal lipid metabolism, while replacement of potassium has been shown to eliminate the risk of arrhythmias as well as thiazide-induced hyperglycaemia. The effect of the thiazide-induced short-term changes in serum lipids is unclear. Present experience suggests that thiazide-induced impairment of glucose tolerance is due to both reduced glucose-stimulated insulin release and increased peripheral resistance to the action of insulin. The blunted initial response of the pancreatic beta-cells to glucose is clearly dependent on serum potassium, and may cause postprandial hyperglycaemia during most of the day and night. This hypothesis is supported by the observation of enhanced glucose and insulin levels after an overnight fast, as well as 60-120 min after glucose challenges. Increased average levels of insulin may eventually cause down-regulation of cellular insulin receptors, i.e. insulin resistance. It is also conceivable that elevated insulin levels may cause hypertriglyceridaemia and possibly other abnormalities of lipid metabolism. Some recent observations indicate that the prognosis in treated hypertensive patients improves if both blood pressure and cholesterol levels are successfully controlled. We therefore emphasize the importance of normalizing serum potassium when using diuretic-based therapies in the treatment of hypertension.

PMID:
2043227
[Indexed for MEDLINE]

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