title: Effects of chronic angiotensin converting enzyme inhibition on glucose tolerance and insulin sensitivity in essential hypertension.
abstract: The relation between the renin-angiotensin-aldosterone (RAA) system and carbohydrate metabolism and insulin sensitivity in essential hypertension has not been investigated systematically. Twenty nondiabetic patients (age, 49 +/- 1 years; body mass index (BMI), 26.1 +/- 0.4 kg/m2) with essential hypertension (blood pressure, 155 +/- 3/105 +/- 1 mm Hg) received an oral glucose tolerance test (OGTT) at the end of a 1-month placebo period and again monthly during 3 months of angiotensin converting enzyme (ACE) inhibition (cilazapril, 5 mg/day). Furthermore, a two-step euglycemic insulin clamp was performed after placebo and again at the end of treatment. Blood pressure fell by 7 +/- 4/10 +/- 3 mm Hg (p less than 0.001), while BMI remained stable. On the euglycemic clamp, insulin-mediated (plasma insulin, 470 pM) whole body glucose use averaged 42.5 +/- 1.6 mumol.min-1.kg-1 before and 43.6 +/- 1.9 after ACE inhibition (p = NS). Substrate concentrations and oxidative rates and energy expenditure (as estimated by indirect calorimetry) were not altered by ACE inhibition, either in the fasting state or in response to insulin. In contrast, oral glucose tolerance was significantly (p less than 0.05) improved after treatment (area under OGTT curve (AUC), 240 +/- 24 versus 282 +/- 23 mmol 2 hr.l-1). The latter change was associated with enhanced (+16%, p less than 0.05) insulin responsiveness to glucose (estimated as the insulin AUC divided by the glucose AUC) throughout the 3 months of ACE inhibition. At baseline, both the OGTT and the clamp had a marked hypokalemic effect (mean decrements in plasma potassium of 0.75 +/- 0.05 and 0.92 +/- 0.05 mmol/l, respectively) in association with plasma aldosterone reductions of 30% and 50%. Chronic ACE inhibition caused a further 20% (p less than 0.03) lowering of plasma aldosterone concentrations but attenuated insulin-induced hypokalemia. Plasma sodium, which was unaltered by the pretreatment tests, fell during the posttreatment tests (by 3 mmol/l, p less than 0.001). In the urine, the ratio of the fractional excretion of potassium to that of sodium was decreased by both oral glucose (-22%, p less than 0.01) and ACE inhibition (-21%, p less than 0.001). Higher plasma potassium levels before treatment predicted a better blood pressure response to ACE inhibition (r = 0.60, p less than 0.005).(ABSTRACT TRUNCATED AT 400 WORDS)
authors.affiliation: Metabolism Unit, C.N.R. Institute of Clinical Physiology, Pisa, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Santoro
authors.forename: A
authors.initials: A
authors.lastname: Natali
authors.forename: C
authors.initials: C
authors.lastname: Palombo
authors.forename: L S
authors.initials: LS
authors.lastname: Brandi
authors.forename: M
authors.initials: M
authors.lastname: Piatti
authors.forename: S
authors.initials: S
authors.lastname: Ghione
authors.forename: E
authors.initials: E
authors.lastname: Ferrannini
mesh_terms: D000284:Administration, Oral; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000502:physiology*; D005951:Glucose Tolerance Test; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000503:physiopathology*; D007328:Insulin / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood; D013997:Time Factors
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007328:Insulin; D012964:Sodium; D005947:Glucose; D011188:Potassium