Response to Acarbose and Postprandial Hypotension
We thank Gentilcore et al1 for their interest in our recent publication. Our work was focused on the potential therapeutic use of acarbose in the prevention of postprandial hypotension in autonomic failure patients rather than an in-depth research into the complex pathophysiology of this process. We did not include, therefore, several important references dealing with the latter, and we are please that, in their letter, they highlighted their significant work in this area.
Many of the proposed mechanisms mentioned in their letter, however, cannot completely explain the mechanism underlying acarbose’s effect in blunting postprandial hypotension. They have shown, eg, that acarbose delays gastric emptying, but as they correctly point out, this effect is only evident 90 minutes after a meal, whereas the prevention of hypotension is seen sooner. They have also shown that acarbose stimulates the secretion of glucagon-like peptide-1 and inhibits the secretion of glucose-dependant insulinotropic polypeptide in response to a meal. These important association studies, however, do not proof causality. Furthermore, acarbose alters the secretion of several other gastrointestinal peptides in response to meals, any or all of which could contribute to its blunting of postprandial hypotension.
Our comments do not detract from the important contributions that Gentilcore et al1 and others have made in this area, but final proof of the role of incretins on postprandial hypotension would require the use of selective antagonists in humans or animal models. In this regard, it is important to note the magnifying effect that the absence of a functional baroreflex has on postprandial hypotension. In the work by Gentilcore et al1 in normal elderly subjects, the maximal decrease in blood pressure after a 100-g sucrose load was only ≈6 mm Hg. By contrast, the average fall in systolic blood pressure after a complex meal containing 52 g of carbohydrates was 34±3 mm Hg in our patients with autonomic failure. It would be possible, therefore, to develop a baroreflex-denervated animal model to study the complex pathophysiology of postprandial hypotension and to test the interesting hypothesis proposed by the authors.
Sources of Funding
This work was supported by grants HL56693 and NS055670 and the General Clinical Research Center grant MOI RR00095.