Elevated hepatic insulin extraction in essential hypertension.

Abstract

Insulin resistance, hyperinsulinemia, and dyslipidemia are common characteristics of patients with untreated hypertension. However, the link between the vascular and metabolic disturbances is still unclear. To provide further insights into the metabolic picture of subjects with hypertension, we evaluated insulin resistance, pancreatic secretion, and hepatic extraction of the hormone in 16 untreated patients with essential hypertension before and after 12-16 weeks of drug treatment in comparison with 16 age-, sex-, and body weight-matched normotensive control subjects. All subjects underwent an oral and a frequently sampled intravenous glucose tolerance test. Metabolic parameters were calculated by the minimal model technique. The hypertensive patients exhibited a highly reduced tissue insulin sensitivity (2.6±0.4 versus 9.6±1.9 10 4 min~V[microunits/mL];p<0.001). The basal secretion rate (70+11 versus 35±5 pmol/L per minute) and the total amount of prehepatically secreted insulin (32±4 versus 16±2 nmol/L in 4 hours) were significantly increased in the hypertensive patients compared with the control subjects (p<0.01), whereas the posthepatic insulin delivery rate was not significantly different between the two groups (4.9±0.6 versus 3.5 ±0.3 nmol/L in 4 hours). Hepatic insulin extraction was found to be significantly elevated in the hypertensive patients compared with control subjects (81±4% versus 69±3%, p<0.04). Increased hepatic insulin extraction partially ameliorated B cell hypersecretion in hypertensive patients. After 12-16 weeks of drug treatment, the blood pressure was normalized, but the metabolic profile of the patients remained unchanged. We conclude that elevated insulin extraction in the liver is a specific characteristic of individuals with essential hypertension and partially compensates pancreatic B cell hypersecretion. {Hypertension 1993;21:646-653) KEY WORDS • hypertension, essential • insulin sensitivity • hepatic insulin extraction T he striking clinical association among hypertension, hyperinsulinemia, and impaired glucose tolerance has attracted considerable attention in recent years, 1 " 3 but despite great scientific effort the etiology and pathogenesis of these diseases and the link between high blood pressure and the metabolic aberrations are still unknown.4 -8 Because these conditions represent predictors for cardiovascular disease and early mortality, it would be of great interest to elucidate the hyperinsulinemia-hypertension link. Moreover, it is still controversial whether drug treatment leads to changes in the metabolic status of patients with essential hypertension and has any effect on coronary artery disease at all.Although several studies give evidence of high peripheral insulin levels in hypertension, 5 -6 -8 there are only a few investigations on dynamic beta cell function and insulin resistance in this state. 6 To our knowledge, the role of hepatic insulin extraction in the pathogen- esis of hyperinsulinemia in essential hypertension has not been elucidated so far. Therefor...

Dynamics of insulin action in hypertension: assessment from minimal model interpretation of intravenous glucose tolerance test data

“…Under our clinical settings, a significant 56% reduction of S I was observed in our normoglycemic, insulin-resistant hypertensive patients, compared to our control N-group (Table 2). This finding is consistent with the well recognized association between insulin resistance and hypertension assessed from traditional, GKMM-based and clamp-based insulin sensitivity indexes [9,10,18,22,23,26,33]. On the other hand, no significant change of glucose effectiveness, S G , between our age-matched H and N groups meets our previous finding that non-insulin-mediated glucose uptake depends on age and is irrespective of insulin resistance [9].…”

“…Significant deterioration of insulin sensitivity in hypertension has been reported after quantification of insulin-sensitivity indexes by the euglycemic-hyperinsulinemic clamp technique [13,18,23], and by applying the glucose kinetics minimal model (GKMM) to interpret insulinemia and glycemia data obtained from either frequently sampled intravenous glucose tolerance test (FSIGTT) [9,22,26,33] or frequently sampled oral glucose tolerance test (FSOGTT) [10]. Among these methods, the GKMM-based interpretation of FSIGTT data has the advantage to provide simultaneous estimates of two other parameters, beyond S I , which are useful to complement the assessment of glucose tolerance.…”

Insulin resistance in young, lean male subjects with essential hypertension

“…21,22 The common occurrence of insulin resistance and HT is frequent owing to the overlapping prevalence of overweight/obesity, diabetes, HT and dyslipidaemia in Western civilization. 11,23 Although HT is more frequent in obese than in normal-weight children, 2 investigation of the mechanisms involved in the onset and development of HT in youth has to be carried out in lean and otherwise healthy hypertensive individuals to exclude as many confounding factors as possible. Our patients were only young, lean men, carefully selected with newly diagnosed HT, who were not pharmacologically treated for any condition and had no history of diabetes; thus, avoiding the most common confounding factors.…”

Insulin and C-peptide secretion and kinetics in humans: direct and model-based measurements during OGTT

“…The model presented in this study also allows estimation of systemic insulin clearance; that in the original version (23) was fixed to values obtained from other studies (10)(11)(12) or from the literature (18,21). The data set of the present study, in fact, allowed estimation of at least one more parameter, maintaining an acceptable accuracy in the estimates.…”