The gut incretin hormone, glucose-dependent insulinotropic polypeptide (GIP), may play a pivotal role in mediating adverse effects of high glycemic index (GI) foods on metabolic diseases. GIP exerts its effects by binding to a receptor, GIPR; genome-wide association studies have identified variants in the GIPR region related to type 2 diabetes (T2D) and glycemic/GIP responses to glucose tolerance tests. We examined whether GIPR variants were related to impaired glycemic responses during oral glucose tolerance tests (OGTTs) after consuming 4 diets (each for 5 weeks) with different carbohydrate (Carb) content and GI levels in the OmniCarb randomized crossover feeding trial. A genetic risk score (GRS) was calculated by counting T2D-risk alleles of SNPs rs1800437, rs11671664, and rs2238689 at GIPR (n=146). We found that GRS was related to greater glycemic responses after consuming a high GI/high Carb diet, regardless of baseline glycemic status (Fig). When testing diet replacement effects, combined effects of high GI and high Carb (vs. low GI/low Carb) on glycemic responses were significantly modified by GRS (Pinteraction<0.05). In conclusion, T2D-risk-related GIPR variants modified the effects of dietary carbohydrates on glucose tolerance. GIPR variants may be related to deteriorating glucose tolerance after eating a high GI, high Carb diet.

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Disclosure

Y.Heianza: None. X.Wang: None. Q.Xue: None. L.J.Appel: None. F.Sacks: None. L.Qi: None.

Funding

National Institutes of Health (2P20GM109036-06A1-7233, DK091718, DK100383, DK115679)

© 2023 by the American Diabetes Association
2023
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