MADRID — Angiotensin I receptor blockade with losartan improves insulin sensitivity independent of its effects on blood pressure in hypertensive individuals at risk for metabolic syndrome, reported Dr. Tonje Aksnes at the annual meeting of the European Society of Hypertension.
Previous studies have shown that blocking the renin-angiotensin system prevents new-onset diabetes to a far greater degree than does pressure control with calcium channel blockers, which suggests that angiotensin receptor blockers (ARBs) have direct effects on glucose metabolism. Calcium channel blockers probably do not have metabolic effects, said Dr. Aksnes of the cardiovascular and renal research centre at Ullevål University Hospital, Oslo.
To test this hypothesis, Dr. Aksnes and colleagues compared two regimens—10 mg/day amlodipine and 100 mg/day losartan plus 5 mg/day amlodipine—in a cohort of 21 subjects with essential hypertension. The patients had a mean age of 59 years and had baseline systolic pressures in the 160–180 mm Hg range and diastolic pressures of 95–110 mm Hg.
All had impaired glucose tolerance or impaired fasting glucose levels, and at least one of the following signs of metabolic syndrome: microalbuminuria, low HDL cholesterol level, elevated triglycerides, waist-to-hip ratio greater than 0.9 for men or 0.85 for women, or body mass index greater than 28 kg/m
After a 4-week run-in period during which all of the patients were given 5 mg/day amlodipine, they were randomised to receive, in addition to the 5 mg/day amlodipine, 100 mg/day losartan or an additional 5 mg/day of amlodipine for 8 weeks. This was followed by a 4-week washout during which all of the patients were again put on 5 mg/day amlodipine alone. For the final phase, the two patient groups were crossed over: Those who were on the ARB during the initial trial phase were switched to the 10-mg calcium channel blocker, and those who were initially on the calcium channel blocker switched to the ARB.
The two drug regimens gave comparable levels of blood pressure control. Amlodipine alone, at a 10 mg daily dosage, reduced mean pressure to 141/88 mm Hg from a baseline mean of 160/96 mm Hg. Losartan reduced pressure to 143/88 mm Hg.
The investigators assessed glucose metabolism by two separate hyperinsulinemic glucose clamp examinations. They found a consistent and significant difference between the two regimens. While the patients were on 10 mg amlodipine alone, they had a mean insulin sensitivity of 4.2 mg/mL per minute. This increased to 4.9 mg/mL per minute while they were on the ARB plus 5 mg amlodipine.
There was no significant difference in HbA1c values between the two treatment regimens. Likewise, blood glucose levels were more or less consistent and unchanged by either treatment. The main impact, it seemed, was on the degree of insulin sensitivity.
“The present data suggest that angiotensin I receptor blockade improves glucose metabolism at the cellular level, beyond what can be expected by the vasodilatation and blood pressure reduction alone,” said Dr. Aksnes.