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Effects of small intestinal glucose on glycaemia, insulinaemia and incretin hormone release are load-dependent in obese subjects

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Abstract

Background/Objectives:

Studies concerning the glycaemic response to oral glucose, or meals in obesity have usually failed to account for gastric emptying. It has been suggested that the incretin effect may be diminished in obesity as a result of a reduction in glucagon-like peptide-1 (GLP-1) secretion. We sought to determine the effect of two different rates of intraduodenal glucose infusions on glycaemic, insulinaemic and incretin hormone responses in lean and obese subjects and compare the effects of oral and intraduodenal glucose in obese subjects.

Subjects/Methods:

Eleven obese subjects (age 37.5±4.1 years, body mass index (BMI) 35.7±1.4 kg m−2) and 12 controls (age 34.7±4.0 years, BMI 23.9±0.7 kg m−2) received intraduodenal infusions of glucose at 1 or 3 kcal min−1, or saline for 60 min (t=0–60 min), followed by intraduodenal saline (t=60–120 min). In obese subjects, an oral glucose tolerance test was performed. Blood glucose, serum insulin, plasma total GLP-1 and total gastric inhibitory polypeptide (GIP) were measured.

Results:

In both the groups (P<0.001), the incremental areas under the curve (iAUC)0–60 min for glucose was greater with the 3 kcal min−1 than the 1 kcal min−1 infusion; the iAUC0–120 min for glucose during 3 kcal min−1 was greater (P<0.05), in the obese. Insulin responses to 1 kcal min−1 and, particularly, 3 kcal min−1 were greater (P<0.001) in the obese. Stimulation of GLP-1 and GIP were greater (P<0.001) in response to 3 kcal min−1, compared with 1 kcal min−1 and saline, without any difference between the groups. In the obese, glycaemic, insulinaemic and GIP, but not GLP-1, responses to oral and intraduodenal glucose were related (P<0.05).

Conclusions:

The rate of duodenal glucose delivery is a major determinant of glycaemia, insulinaemia and incretin hormone release in obese subjects. Obesity is not apparently associated with impaired GLP-1 secretion.

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Acknowledgements

We would like to acknowledge Mrs Rachael Tippett (Discipline of Medicine, University of Adelaide) for providing technical assistance with the studies. This study was supported by the National Health and Medical Research Council (NHMRC) of Australia (grant 627189). KLJ’s salary is funded by an NHMRC Senior Career Development Award (grant 627011) and CFB’s salary is funded by an NHMRC Senior Research Fellowship (grant 1103020). LGT was supported by an Australian Postgraduate Award and a Dawes scholarship from the Royal Adelaide Hospital.

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Authors and Affiliations

  1. Discipline of Medicine, University of Adelaide, Adelaide, South Australia, Australia

    L G Trahair, C S Marathe, S Standfield, C K Rayner, C Feinle-Bisset, M Horowitz & K L Jones

  2. NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, South Australia, Australia

    L G Trahair, C S Marathe, S Standfield, C K Rayner, C Feinle-Bisset, M Horowitz & K L Jones

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  1. L G Trahair
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Correspondence to K L Jones.

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Competing interests

MH has participated in the advisory boards and/or symposia for Novo Nordisk, Sanofi, Novartis, Eli Lilly, Merck Sharp and Dohme, Boehringer Ingelheim and AstraZeneca, and has received honoraria for this activity. CKR has received research funding from Merck, AstraZeneca and Novartis. The remaining authors declare no conflict of interest.

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Trahair, L., Marathe, C., Standfield, S. et al. Effects of small intestinal glucose on glycaemia, insulinaemia and incretin hormone release are load-dependent in obese subjects. Int J Obes 41, 225–232 (2017). https://doi.org/10.1038/ijo.2016.202

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