title: Acarbose, an alpha-glucosidase inhibitor, attenuates postprandial hypotension in autonomic failure.
abstract: Postprandial hypotension is an important clinical condition that predisposes to syncope, falls, angina, and cerebrovascular events. The magnitude of the fall in blood pressure after meals depends on enteric glucose availability. We hypothesized that acarbose, an alpha-glucosidase inhibitor that decreases glucose absorption in the small intestine, would attenuate postprandial hypotension. Acarbose or placebo was given 20 minutes before a standardized meal in 13 patients with postprandial hypotension in the setting of autonomic failure (age: 65+/-2.64 years; body mass index: 25+/-1.08 kg/m(2); supine plasma norepinephrine: 110+/-26.6 pg/mL). Four patients were studied in a single-blind protocol and 9 patients in a double-blind, randomized, crossover fashion. Patients were studied supine, and blood pressure, heart rate, and neuroendocrine parameters were obtained at baseline and for 90 minutes after meal intake. After adjusting for potential confounders, acarbose significantly attenuated the postprandial fall in systolic and diastolic blood pressures by 17 mm Hg (95% CI: 7 to 28; P=0.003) and 9 mm Hg (95% CI: 5 to 14; P=0.001), respectively. Furthermore, acarbose effectively reduced plasma levels of insulin, a known vasodilator, by 11 microU/mL (95% CI: 5 to 18; P=0.001) compared with placebo. After adjusting for insulin levels, the attenuation of postprandial hypotension by acarbose remained significant, indicating that additional mechanisms contribute to this effect. In conclusion, 100 mg of acarbose successfully improved postprandial hypotension in patients with severe autonomic failure. This effect is not explained solely by a reduction in insulin levels.
authors.affiliation: Department of Medicine, Division of Clinical Pharmacology and the Autonomic Dysfunction Center, Vanderbilt University School of Medicine, Nashville, TN 37212, USA.
authors.forename: Cyndya
authors.initials: C
authors.lastname: Shibao
authors.forename: Alfredo
authors.initials: A
authors.lastname: Gamboa
authors.forename: Andre
authors.initials: A
authors.lastname: Diedrich
authors.forename: Cynthia
authors.initials: C
authors.lastname: Dossett
authors.forename: Leena
authors.initials: L
authors.lastname: Choi
authors.forename: Ginnie
authors.initials: G
authors.lastname: Farley
authors.forename: Italo
authors.initials: I
authors.lastname: Biaggioni
mesh_terms: D020909:Acarbose / Q000627:therapeutic use*; D000368:Aged; D001341:Autonomic Nervous System / Q000503:physiopathology; D001342:Autonomic Nervous System Diseases / Q000150:complications* / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D002319:Cardiovascular System / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D065089:Glycoside Hydrolase Inhibitors; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007022:Hypotension / Q000188:drug therapy* / Q000209:etiology* / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D009490:Neurosecretory Systems / Q000187:drug effects / Q000503:physiopathology; D019518:Postprandial Period; D016037:Single-Blind Method
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D007328:Insulin; D020909:Acarbose