Effects of exogenous glucagon-like peptide-1 on the blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in healthy older subjects and type 2 diabetes. — ASN Events
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Effects of exogenous glucagon-like peptide-1 on the blood pressure, heart rate, gastric emptying, mesenteric blood flow and glycaemic responses to oral glucose in healthy older subjects and type 2 diabetes. (#92)

Laurence G Trahair 1 2 , Michael Horowitz 1 2 , Julie E Stevens 3 , Christine Feinle-Bisset 1 2 , Scott Standfield 1 2 , Diana Piscitelli 1 4 , Christopher K Rayner 1 2 , Adam M Deane 5 6 , Karen L Jones 1 2
  1. Discipline of Medicine, The University of Adelaide, Adelaide, South Australia, Australia
  2. NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health, The University of Adelaide, Adelaide, South Australia, Australia
  3. School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, South Australia, Australia
  4. School of Health Sciences, University of South Australia, Adelaide, South Australia, Australia
  5. Intensive Care Unit, Royal Adelaide Hospital, Adelaide, South Australia, Australia
  6. Discipline of Acute Care Medicine, The University of Adelaide, Adelaide, South Australia, Australia

Background: A postprandial fall in blood pressure (BP) occurs frequently in the ‘healthy’ elderly and patients with type 2 diabetes, the magnitude of which is related to the rate of gastric emptying (GE) and rise in splanchnic blood flow. Postprandial hypotension (PPH) is an important clinical problem in these groups for which current management is suboptimal. We have reported that, in healthy older subjects, intravenous GLP-1 attenuates the hypotensive response to an intraduodenal glucose infusion, but increases superior mesenteric artery (SMA) blood flow1.
Aim: To determine the effects of exogenous GLP-1 on the BP, GE, SMA flow and glycaemic responses to oral glucose in healthy older subjects and type 2 patients.
Methodology: 14 healthy older subjects (6M,8F; age 72.1±1.1 years) and 10 type 2 patients (6M,4F; age 68.7±3.4 years, HbA1c 6.6±0.2%, 9 managed with metformin, two sulfonylurea and one a DPP-4 inhibitor) received intravenous GLP-1 (0.9 pmol/kg/min) or saline (0.9%) for 150 min (t= -30–120 min) in randomised order. At t= 0 min, they consumed a 300mL drink containing 75g glucose, labelled with 20MBq 99mTc-calcium phytate. BP was measured with an automated device (DINAMAP), GE by scintigraphy and SMA flow by duplex ultrasonography. Blood glucose and serum insulin were measured.
Results: In both groups, systolic BP fell after the glucose drink (P< 0.05). GLP-1 attenuated the fall in diastolic BP in older subjects (P< 0.05) and both systolic and diastolic BP in type 2 patients (P< 0.05) (Figure 1). GE during the control condition was faster in type 2 patients than healthy subjects (87.7±10.4 min vs. 121.7±11.7 min, P< 0.05). In both groups, GE was slower (P< 0.001), and both SMA flow (P< 0.05) and glycaemia (P< 0.001) less, with GLP-1.
Conclusions: Acute intravenous administration of GLP-1 attenuates the hypotensive response to oral glucose and decreases SMA flow and glycaemia in healthy older subjects and type 2 patients, probably by slowing GE. These observations suggest that exogenous GLP-1 and ‘short-acting’ GLP-1 agonists may be useful in the management of PPH.

Figure 1:

2098-BPHR.jpg

  1. Trahair et al, J Clin Endocrinol Metab, 2014, 99: E2628-2634