Effects of exenatide on the blood pressure and heart rate responses to intraduodenal glucose in type 2 diabetes — ASN Events

Effects of exenatide on the blood pressure and heart rate responses to intraduodenal glucose in type 2 diabetes (#168)

Sony S Thazhath 1 , Chinmay S Marathe 2 , Tonghzhi Wu 1 , Jessica Chang 1 , Joan Khoo 3 , Paul Kuo 4 , Karen Jones 1 , Michael Horowitz 2 , Christopher K Rayner 1 4
  1. Discipline of Medicine , University of Adelaide / Royal Adelaide Hospital , Adelaide , SA , Australia
  2. Discipline of Medicine , Endocrine & Metabolic Unit, Royal Adelaide Hospital / University of Adelaide , Adelaide , SA, Australia
  3. Department of Endocrinology, Changi General Hospital , Singapore
  4. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital , Adelaide , SA , Australia

Postprandial hypotension occurs frequently, particularly in older individuals and patients with type 2 diabetes, and represents a major cause of morbidity and mortality. We have recently reported that acute administration of glucagon-like peptide-1 (GLP-1) attenuates the hypotensive response to intraduodenal (ID) glucose infusion (‘bypassing’ the potential impact of gastric emptying) in healthy older subjects. In this study, we have evaluated the effects of the GLP-1 receptor agonist, exenatide, on the blood pressure (BP) and heart rate (HR) responses to an ID glucose infusion in type 2 diabetes.

 

Nine patients with diet-controlled type 2 diabetes (mean age (±SEM) 60.4±2.3yr; BMI 29.11.5kg/m2; HbA1c 6.1±0.2% (43.4±2.6mmol/mol); duration of diabetes 63.3±14.0 months) were studied in the supine position on two occasions each in double-blind, randomised fashion. After an overnight fast, exenatide (50ng/min from t = -30-0min; then 25ng/min) or saline control was administered by iv. infusion, with concurrent ID glucose infusion from t = 0-60min at 3kcal/min. Systolic and diastolic BP (SBP, DBP), and HR were measured at frequent intervals with an automated device. Gastrointestinal sensations were evaluated using 100mm visual analogue scales.

 

Prior to ID glucose infusion, there were no differences in SBP or DBP, or HR between the two study days. In response to ID glucose infusion, there was a fall in DBP (P=0.009) and a rise in HR on the control days (P<0.001), without a significant change in SBP. In contrast, SBP (P=0.002), DBP (P=0.023) and HR (P<0.001) were all increased from baseline on the exenatide days, and were higher than on the control days (P<0.05 for each). In addition, nausea scores did not differ between the two study days before ID glucose infusion, but increased by ~13% during ID glucose infusion with exenatide than control.

 

In type 2 diabetes, exenatide acutely attenuates the fall in DBP and increases HR in response to ID glucose, warranting further evaluation of GLP-1 agonists in the management of postprandial hypotension.

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