Effects of endogenous and exogenous glucose dependent insulinotropic polypeptide on blood pressure, heart rate, gastric emptying and blood glucose responses to oral glucose in healthy older people
Date
2024
Authors
Jalleh, R.J.
Hatzinikolas, S.
Slavotinek, A.C.
Kamruzzaman, M.
Lange, K.
Malbert, C.H.
Veedfald, S.
Gasbjerg, L.S.
Rosenkilde, M.M.
Holst, J.J.
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Journal Title
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Conference item
Citation
Diabetologia, 2024, vol.67, iss.Suppl 1, pp.S47-S47
Statement of Responsibility
R.J. Jalleh, S. Hatzinikolas, A.C. Slavotinek, M. Kamruzzaman, K. Lange, C.H. Malbert, S. Veedfald, L.S. Gasbjerg, M.M. Rosenkilde, J.J. Holst, C.S. Marathe, T. Wu, C.K. Rayner, M. Horowitz, K.L. Jones
Conference Name
EASD Annual Meeting of the European Association for the Study of Diabetes (10 Sep 2024 - 13 Sep 2024 : Madrid, Spain)
Abstract
Background and aims: Postprandial hypotension (PPH), a fall in blood pressure (BP) >20mmHg following a meal, occurs in ~ 15-20% of healthy people > 65 years and ~35% of people with type 2 diabetes. It is associated with a markedly increased risk of falls and is an independent predictor of mortality. The fall in BP refects the increase in splanchnic blood fow and is greater when gastric emptying is more rapid. Glucagon-like peptide-1 (GLP-1) and GLP-1 receptor agonists attenuate the postprandial fall in BP, in part by slowing gastric emptying. In contrast to GLP-1, the efects of glucose dependent insulinotropic polypeptide (GIP) on BP and gastric emptying are poorly defned. We have used the specifc GIP receptor antagonist, GIP(3-30)NH2, to assess the efect of GIP on the BP, heart rate (HR), gastric emptying and blood glucose responses to a glucose drink in healthy older people. Materials and methods: 18 healthy older participants (13F, 5M; mean age 67.7±0.7 years; BMI 28.1±0.9 kg/m2 ) attended the laboratory on 3 occasions after an overnight fast. Intravenous cannulae were inserted into both arms for blood sampling and intravenous infusion of (i) GIP (1.5 pmol/kg/min), (ii) GIP(3-30)NH2 (800 pmol/kg/min) or (iii) 0.9% saline (placebo) for 240min (t=-30-210min) in a randomised, double-blind, cross-over design. Participants were seated and BP, mean arterial pressure (MAP) and HR monitored using an automated device. At t=-2 min participants ingested a 75g glucose drink (300ml) radiolabelled with 20MBq 99mTc-calcium phytate to assess gastric emptying by scintigraphy, and at t=180min they were ofered a bufet style lunch. Data are means±SEM. Results: All studies were well-tolerated. There was a modest slowing of gastric emptying by exogenous GIP (P<0.05) with no efect of GIP(3-30)NH2. Exogenous GIP and GIP(3-30)NH2 had no efect on MAP, HR or blood glucose during the fasting period. Following the glucose drink, MAP fell (P<0.01) on all study days. The magnitude of the fall in MAP (P=0.03), and rise in HR (P=0.01) was less after GIP(3-30)NH2 compared to placebo (Figure). Peak blood glucose was greater (P<0.001) after GIP(3-30)NH2 (12.2±0.4 mmol/L), with no efect of exogenous GIP (10.6±0.4 mmol/L) when compared to placebo (10.6±0.5 mmol/L). Conclusion: In healthy older people, the fall in BP and rise in HR after oral glucose are attenuated when GIP release is blocked. Accordingly, endogenous GIP, beyond its established role in glucose metabolism, modulates postprandial cardiovascular responses.
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Section - OP 14 Incretins: How many targets do you
need? Abstract #84
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