Four week administration of an ACE inhibitor and a cardioselective β‐blocker in healthy volunteers: no influence on insulin sensitivity

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Abstract
In most, but not all, studies antihypertensive treatment with angiotensin converting enzyme inhibitors (ACE inhibitors) improves insulin sensitivity, whereas β‐blockers decrease insulin sensitivity. However, there was a significant increase in body weight with β‐blockers and changes in the body potassium homeostasis with ACE inhibitors. In order to compare the drug specific metabolic effects of an ACE inhibitor and a cardioselective β‐blocker controlling these factors, we measured insulin sensitivity in a randomized, double‐blind cross‐over study in 22 healthy volunteers (age 27 ± 3 years; BMI 22.0± 1.5kg m‐2 (mean ± SD)) during euglycaemic glucose clamps before and after 4 weeks' administration of 5mg Lisinopril or 5mg Bisoprolol. Both drug phases were separated by 4 weeks of no drug administration. During the insulin sensitivity measurements potassium concentrations were clamped at basal levels by means of a variable i.v. potassium infusion. Body weight was monitored at weekly intervals and kept constant within ± 1 kg of the subjects' baseline weight throughout the entire study period. Insulin sensitivity did not change significantly during either drug administration period. The insulin sensitivity index of the 22 volunteers after administration of the ACE inhibitor was 7.9±2.4 mL min‐1 m2μU‐1 mL‐1 (basal index 8.3 ± l.9mL min‐1 m2μ‐1 mL‐1, and 7.5 ± 2.1 mL min‐1 m2μU‐1 mL‐1 after administration of the β‐blocker (basal index 8.2 ± l.9mL min‐1 m2μ=‐1 mL‐1; NS). In order to maintain blood potassium concentrations during the glucose c lamps at basal levels of 3.9 ± 0.3 mmol l‐1 a mean of 7.9±4.2 mval of potassium had to be infused during the low insulin step and a mean of 24.1 ±9.7mval during the high insulin step. Systolic and diastolic blood pressure were lowered significantly by Lisinopril (5±8 mmHg and 7 ± 9 mmHg) and Bisoprolol (7 ± 7 mmHg and 4 ± 8 mmHg; NS between both drugs), respectively. In healthy normo‐tensive subjects administration of Lisinopril or Bisoprolol for 4 weeks does not influence insulin sensitivity, when appropriate experimental conditions are maintained.

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