Attenuation of Postprandial Hypotension with Acarbose in Older Adults with Type 2 Diabetes Mellitus

To the Editor: Postprandial hypotension (PPH), when systolic blood pressure (SBP) decreases more than 20 mmHg after eating, is a common cause of fainting-induced falls.1 PPH has also been shown to be an independent predictor of mortality in older adults.2 The purpose of the present pilot study was to examine whether blocking carbohydrate intake in the small intestine with acarbose (an alpha-glucosidase inhibitor) would attenuate the postprandial hypotensive response in older adults with diabetes mellitus complicated by PPH. All subjects were aged 65 and older and had a diagnosis of type 2 diabetes mellitus as defined by current American Diabetes Association guidelines, a normal hematocrit, and normal creatinine.3 Subjects were excluded if they took insulin (because of the known vasoactive effects)4 or had orthostatic hypotension. This study received approval from the human subjects committee of the University of British Columbia, and all subjects provided written informed consent. The study had a randomized, double-blind, placebo-controlled, crossover design with allocation concealment. Subjects were examined in a fasting state at 9:30 a.m., and each meal test lasted 90 minutes. All antihypertensive medications were held until after completion of the study that morning. Subjects were given acarbose 50 mg or a placebo immediately before administration of the liquid standardized meal (1,050 kJ; containing 7.8 g fat, 38 g carbohydrates, 9.4 g protein, and 3.4 g fiber; 3.0 ± 0.5°C). Beat-to-beat heart rate measures (three-lead electrocardiogram), blood pressure (Finometer, Finapres Medical Systems BV, Amsterdam, the Netherlands) and cerebral Doppler (2 MHz TCD probe, Spencer Technologies, Northborough, MA) were sampled at 1,000 Hz. Repeated-measures two-way analysis of variance was used to compare the main effect of time, the main effect of study session, and the interaction term (time by session) for all parameters. Fifteen older adults (six male, nine female; mean age 76 ± 1, range 67–85) were recruited; there were no dropouts. Baseline SBP (128 ± 5 vs 113 ± 5, P = .087), DBP (73 ± 4 vs 67 ± 4, P = .064), and MAP (93 ± 4 and 86 ± 4, P = .08) were not significantly different between the two sessions. Fourteen of the 15 subjects had at least one postprandial hypotensive episode during the placebo session. Subjects had 0.7 (95% confidence interval = 0.1–1.2, bootstrap analysis) fewer PHEs during the acarbose session (0.8 ± 0.2 PHEs, bootstrap analysis) than during the placebo session (1.5 ± 0.3 PHEs, bootstrap analysis). No subjects experienced presyncopal or syncopal symptoms during any of the study sessions. There was an overall significant main effect of time on SBP (P < .001), mean arterial pressure (MAP) (P < .001), diastolic blood pressure (DBP) (P < .001), and heart rate (P < .001) during the postprandial period. Subjects had significantly higher postprandial SBP (session, P = .03) and MAP (session, P = .03) during the acarbose session but not for DBP (session, P = .07) or heart rate (P = .69) (Figure 1). The interaction terms for SBP (time by session, P = .22) and MAP (time by session, P = .03) were not significant. Subjects experienced significantly lower systolic (session, P < .02; time by session, P < .001), mean (session, P = .03; time by session, P = .03), and diastolic (session, P < .04; time by session, P = .003) middle cerebral arterial (MCA) velocities during the acarbose session. The difference between the placebo and acarbose sessions tended to widen during the postprandial period, reaching a plateau after 25 minutes. Current therapy for PPH consists of dietary manipulations, which are poorly tolerated and are suboptimal in effectiveness.5 In a small study (n = 9), acarbose attenuated PPH in a young population without diabetes mellitus with severe autonomic failure;6 acarbose also attenuated normal postprandial physiological changes (n = 8) in older adults without PPH.7 The only investigations of acarbose in older adults with PPH were found in case reports.8 To the knowledge of the authors of the current study, this study was the first to demonstrate that a single dose of an alpha-glucosidase inhibitor elevates postprandial blood pressure, resulting in a reduction in the number of PHEs in older adults with PPH. In addition to effects on the postprandial hemodynamic response, acarbose reduced postprandial MCA velocities. MCA velocity is proportional to MCA blood flow and proportional to the inverse of the square of the MCA diameter.9 Given that blood pressures were consistently higher in the postprandial acarbose session, it is likely that acarbose increased MCA diameter through an improvement in the cerebral autoregulatory response, similar to that observed in the peripheral forearm circulation.10 The current study suggests that acarbose might be a useful therapy for PPH in older adults with type 2 diabetes mellitus. Conflicts of Interest: None of the authors have relevant conflict of interests to disclose. This research was supported by the Canadian Diabetes Association (OG-3–13–4157). Author Contributions: Madden: protocol design, data collection and analysis, writing the manuscript. Harris: data collection and analysis, editing the manuscript. Meneilly: protocol design, editing the manuscript. The guarantor for this work is Dr. Kenneth Madden. Sponsor's Role: The sponsor had no role in the design, methods, subject recruitment, data collection, analysis, or preparation of the paper.

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