Acarbose, an α-Glucosidase Inhibitor, Attenuates Postprandial Hypotension in Autonomic Failure

Abstract

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 ␣-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: 65Ϯ2.64 years; body mass index: 25Ϯ1.08 kg/m 2 ; supine plasma norepinephrine: 110Ϯ26.6 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; Pϭ0.003) and 9 mm Hg (95% CI: 5 to 14; Pϭ0.001), respectively. Furthermore, acarbose effectively reduced plasma levels of insulin, a known vasodilator, by 11 U/mL (95% CI: 5 to 18; Pϭ0.001) 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. Key Words: postprandial Ⅲ hypotension Ⅲ acarbose Ⅲ ␣-glucosidase inhibitor Ⅲ autonomic nervous system diseases Ⅲ autonomic failure P ostprandial hypotension (PPH), defined as a fall in systolic blood pressure (SBP) of Ͼ20 mm Hg occurring within 2 hours after a meal, 1,2 is an important clinical problem that predisposes to syncope, falls, angina pectoris, and cerebrovascular events. 3,4 The clinical presentation is characterized by symptoms of lightheadedness with an onset within 30 minutes after food ingestion. 5 The magnitude of the decrease in blood pressure depends on the size of the meal 6 and its composition 4,7 ; PPH is more severe the greater the carbohydrate content. 8 Those most affected are patients with some degree of autonomic impairment, suggesting that, in healthy subjects, the hypotensive effect of meals is buffered by the autonomic nervous system. PPH has been reported in healthy elderly persons, 9,10 elderly patients with hypertension, 11-13 elderly residents of nursing homes, 14,15 patients with Parkinson disease, 16 -18 and patients with diabetes mellitus. 19 PPH is particularly severe in patients suffering from primary forms of autonomic failure. 1 The pathogenesis of PPH is likely multifactorial. Gastrointestinal and pancreatic hormones with vasodilatory properties seem to play a key role. These are released into the bloodstream in response to ...

Acarbose and Postprandial Hypotension

“…2 Conversely, gastric "distension" appears to attenuate the postprandial fall in blood pressure. In 8 healthy older subjects, we, like Shibao et al, 1 reported that acarbose (100 mg) attenuated the fall in systolic blood pressure and increase in heart rate induced by oral carbohydrate (100 g of sucrose in 300 mL of water), and, as expected, suppressed postprandial glycemia and insulinemia. 5 Although these effects may be attributable to slowing of the small intestinal digestion of carbohydrate, acarbose also retarded gastric emptying substantially (and, accordingly, both decreased the delivery of nutrients to the small intestine and prolonged gastric distension), although this was only evident Ϸ90 minutes after the drink, whereas the fall in systolic blood pressure was evident well before this time.…”

“…We read with interest the article by Shibao et al, 1 who reported that acute administration of acarbose had a substantial, beneficial effect on the hypotensive response to a high-carbohydrate meal in patients with autonomic failure. It was suggested that this effect is mediated, at least in part, by a reduction in the insulinemic response to a meal.…”

Chronobiology and Pharmacologic Modulation of the Renin–Angiotensin–Aldosterone System in Dogs: What Have We Learned?

“…As discussed above, the increased natriuresis observed after food intake is reflective of the "impulse-response pattern" of sodium excretion. The marked post-meal drop in systolic and diastolic BP would be the result of reduced RA levels combined with the secretion of vasodilatory gut peptides, such as neurotensin and insulin (Shibao et al 2007). Note that the decrease in RA and BP could also reflect the predominance of parasympathetic activity during the postprandial state, as described by Kobayashi and Kamiya (1997).…”

Effect of Diet on the Cardiovascular System in Healthy Beagles

“…Secretion of gut peptides with known vasodilatory action, such as insulin and neurotensin, is part of the cause of the meal-induced decline in BP in humans [15]. In dogs, the mechanism of decline of BP after feeding time may be the same as in humans because the digestion and absorption systems of dogs are analogous to those in humans.…”