Alpha 1-blocker doxazosin improves peripheral insulin sensitivity in diabetic hypertensive patients.
The antihypertensive doxazosin is a selective alpha 1-adrenoceptor-blocking drug whose favorable impact on lipid metabolism is well known. A single-blind placebo-controlled crossover study was designed to determine whether antihypertensive treatment with doxazosin affects insulin sensitivity in diabetic, mildly hypertensive, non-obese patients. Twelve subjects (diastolic blood pressure, 98 +/- 1.5 mm Hg; body mass index, 25 +/- 0.6 kg/m2; hemoglobin A1c [HbA1c], 7.6% +/- 0.4%) who were not taking drugs and were treating diabetes only by diet were randomly assigned to placebo treatment for 6 weeks and then to doxazosin for the same period, or vice versa. The doxazosin dose (maximum, 12 mg/d) was increased to achieve a normotensive blood pressure (final diastolic pressure, 85 +/- 2 mm Hg, P < .05). A euglycemic (100 +/- 4 mg/dL) hyperinsulinemic (61 +/- 6 microU/mL) glucose clamp was performed at baseline and at the end of both placebo and doxazosin administration. Hepatic glucose production was measured by the isotope dilution technique using 3H-glucose. Body weights and HbA1c did not vary during the entire study. The basal mean glucose uptake and the insulin sensitivity index (2.3 +/- 0.3 mg/kg/min and 4 +/- 0.5 mg/kg/min per U/L x 100) remained unchanged during placebo administration (2.5 +/- 0.4 and 4 +/- 0.6, NS), but significantly increased during doxazosin treatment (3.3 +/- 0.4 and 5.6 +/- 0.7, P < .05). Hepatic glucose production showed no modification during both placebo and doxazosin. These data provide evidence that doxazosin improves insulin sensitivity in diabetic hypertensive patients, mainly through peripheral effects.
Giorda
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Servizio di Diabetologia, Ospedale Maggiore, Chieri, Italy.
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Mason
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D000317:Adrenergic alpha-Antagonists / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D001794:Blood Pressure; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000178:diet therapy / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000097:blood / Q000188:drug therapy*; D003927:Diet, Diabetic; D017292:Doxazosin / Q000627:therapeutic use*; D005260:Female; D015309:Glucose Clamp Technique; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D011865:Radioisotope Dilution Technique; D016037:Single-Blind Method; D013997:Time Factors; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D007328:Insulin; D014316:Tritium; D017292:Doxazosin