Abstract MP61: Starch Digestion-Related Amylase Genetic Variants, Dietary Carbohydrates, and Changes in Glucose Tolerance: Results From the OmniCarb Trial

Abstract

Introduction: Salivary amylase, encoded by the AMY1 gene, plays a pivotal role in carbohydrate digestion, and genetic adaptation of carbohydrate digestion has been implicated in impaired glucose tolerance, type 2 diabetes, and cardiometabolic diseases. Hypothesis: We investigated whether AMY1 genetic variations are associated with β-cell function and glycemic responses during 2-h oral glucose tolerance tests (OGTTs) and tested whether AMY1 variations were related to changes in glucose tolerance in a randomized controlled trial testing effects of diets varying in glycemic index (GI) levels and carbohydrate (Carb) amount. Methods: The study included participants (n=146) from the OmniCarb trial, a randomized crossover-controlled feeding trial, in which overweight or obese adults were given 4 diets that differed in composition by GI and Carb amount. Each diet was consumed for 5 weeks, followed by a 2-week washout. Genetic risk score (GRS) was calculated using eight AMY1 SNPs, with higher GRS indicating higher activity of salivary amylase. The primary outcomes were glycemic and insulin responses during OGTTs. Results: At baseline, lower GRS was related to a larger area under the curve of glucose (AUC-glucose) and β-cell dysfunction assessed by the insulinogenic index and disposition index ( p <0.05 for all). After consuming either a high-Carb and low-GI diet or a low-Carb and high-GI diet for 5 weeks, participants with low GRS (tertile 1) showed impaired glycemic responses at 30, 60, and 90 min after OGTTs, as compared to those with high GRS (tertile 3); there was no significant difference according to GRS after eating a low-Carb/low-GI diet. After consuming a high-Carb and high-GI diet for 5 weeks, the participants with low GRS showed a mean 21 (SE 10) mg/dl higher glucose concentrations at 60 min after OGTT, as compared to those with high GRS ( p =0.038). The effect of increasing GI at low Carb amount for glucose levels at 60 min ( P interaction = 0.024) and AUC-glucose ( P interaction =0.016) significantly interacted with the GRS. Also, we found a significant interaction between GRS and the effect of increasing Carb amount at high GI for 60-min post-load glucose levels ( P interaction = 0.016). Conclusions: The AMY1 genetic variations were associated with β-cell function and impaired glucose tolerance. Effects of changing the amount or quality of carbohydrates on glucose tolerance may be partly determined by individual genetic adaptation of carbohydrate digestion.