Mariëtte Boon¹, Carlijn Hoekx², Robin van Eenige², Lisa Brinkman², Borja Martinez-Tellez³, Patrick Rensen³

(1) Erasmus MC / Endocrinology, Rotterdam, the Netherlands. (2) LUMC / Endocrinology, Leiden, the Netherlands. (3) University of Almería / Department of Nursing Physiotherapy and Medicine, Almaría, Spain.

Background:

South Asians exhibit an unfavorable metabolic phenotype that is characterized by visceral obesity, insulin resistance and dyslipidemia. Since various hormones are critical for regulating energy metabolism, we aimed to study the meal-induced excursion of incretin hormones and glucagon and parameters related to glucose and lipid metabolism in young, lean South Asian and Europid males and females.

Method:

49 young (age 18-30 years, including both genders), lean (body mass index 18.5-25.0 kg/m2) South Asian (n=24), and Europid (n=25) participants underwent an extended (up to 240 min) mixed meal tolerance test (MMTT). At seven time points during the MMTT, circulating incretins (active and total GLP-1 and GIP), glucagon, and parameters related to glucose and lipid metabolism were measured.

Results:

While a single peak (t=30 min) in circulating glucose levels was observed in Europid males and females, a biphasic peak (t=30 and t=90 min) was observed in South Asian males and females. Similarly, South Asians exhibited a biphasic insulin response, with a higher total area under the curve (tAUC_0-240) observed in males. These effects were accompanied by a more profound drop in circulating glucagon at t=90 min especially in South Asian females, and biphasic peaks of total and active GLP-1 and GIP (t=30 and t=120 min onwards) in South Asian females, resulting in significantly increased tAUC_60-240 for active GLP-1 and GIP in South Asian compared to Europid females.

Conclusion:

South Asians respond differently to an MMTT compared to Europids, with a noticeable biphasic peak in glucose levels, and, potentially as a consequence, a higher second peak of active GLP-1 and GIP, especially in South Asian compared to Europid females. This was accompanied by a biphasic insulin response in South Asians compared to Europids. We speculate that these effects result from biphasic gastric emptying in South Asians, while the precise contribution of these effects to the disadvantageous metabolic phenotype of South Asians remains to be determined.