Effects of exogenous glucagon-like peptide-1 on blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in older individuals with normal glucose tolerance or type 2 diabetes.

Laurence G Trahair, Michael Horowitz, Julie E Stevens, Christine Feinle-Bisset, Scott Standfield, Diana Piscitelli, Christopher K Rayner, Adam M Deane, Karen L Jones

Index: Diabetologia 58 , 1769-78, (2015)

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Abstract

A postprandial fall in BP occurs frequently in older individuals and in patients with type 2 diabetes. The magnitude of this decrease in BP is related to the rate of gastric emptying (GE). Intravenous administration of glucagon-like peptide-1 (GLP-1) attenuates the hypotensive response to intraduodenal glucose in healthy older individuals. We sought to determine the effects of exogenous GLP-1 on BP, GE, superior mesenteric artery (SMA) flow and glycaemic response to oral ingestion of glucose in healthy older individuals and patients with type 2 diabetes.Fourteen older volunteers (six men, eight women; age 72.1 ± 1.1 years) and ten patients with type 2 diabetes (six men, four women; age 68.7 ± 3.4 years; HbA1c 6.6 ± 0.2% [48.5 ± 2.0 mmol/mol]; nine with blood glucose managed with metformin, two with a sulfonylurea and one with a dipeptidyl-peptidase 4 inhibitor) received an i.v. infusion of GLP-1 (0.9 pmol kg(-1) min(-1)) or saline (154 mmol/l NaCl) for 150 min (t = -30 min to t = 120 min) in randomised order. At t = 0 min, volunteers consumed a radiolabelled 75 g glucose drink. BP was assessed with an automated device, GE by scintigraphy and SMA flow by ultrasonography. Blood glucose and serum insulin were measured.GLP-1 attenuated the fall in diastolic BP after the glucose drink in older individuals (p < 0.05) and attenuated the fall in systolic and diastolic BP in patients with type 2 diabetes (p < 0.05). GE was faster in patients with type 2 diabetes than in healthy individuals (p < 0.05). In both groups, individuals had slower GE (p < 0.001), decreased SMA flow (p < 0.05) and a lower degree of glycaemia (p < 0.001) when receiving GLP-1.Intravenous GLP-1 attenuates the hypotensive response to orally administered glucose and decreases SMA flow, probably by slowing GE. GLP-1 and 'short-acting' GLP-1 agonists may be useful in the management of postprandial hypotension.