Insulin resistance and upper-normal glucose levels in hypertension: a review

Reduced insulin-mediated glucose disposal, indicative of insulin resistance, has been demonstrated in lean male hypertensives both with the hyperinsulinaemic euglycaemic clamp and the insulin suppression test. In lean hypertensives, insulin resistance was not accompanied by increases in fasting plasma insulin and glucose levels; but with modest hyperglycaemia and hyperinsulinaemia after a glucose load. Population studies (no stratification) reveal that: (1) insulin sensitivities vary widely in normotensives and hypertensives, (2) there are hypertensives and normotensives with similar degrees of insulin resistance, (3) not all hypertensives are insulin resistant, and (4) insulin resistance does not contribute to the blood pressure level of the hypertensive population. In large cross-sectional studies, the clustering of obesity, dyslipidaemia and type 2 diabetes is largely responsible for the observed associations between insulin or insulin resistance and hypertension. Recent studies indicate a role of glucose in blood pressure control. Glucose has been shown to elevate blood pressure in the presence of endothelial dysfunction and glucose values in the upper-normal range have been shown to be associated with increased cardiovascular mortality. Since endothelial dysfunction is present in hypertensives, dyslipidaemic, obese and in glucose intolerant individuals, lowering of high-normal glucose levels becomes a new, additional therapeutic target in the management of these patients. Hyperglycaemia together with endothelial dysfunction may account for the increased incidence of hypertension in obesity and diabetes mellitus. Because of the strong association between insulin resistance, hyperglycaemia and endothelial dysfunction, and the clustering of risk factors in these subjects, we propose the lowering of high normal glucose levels as part of the therapeutic strategy to prevent cardiovascular and metabolic disease.