Genetic Variation in the Glucose-Dependent Insulinotropic Polypeptide Receptor Modifies the Association between Carbohydrate and Fat Intake and Risk of Type 2 Diabetes in the Malmö Diet and Cancer Cohort

Context:

A common genetic variant (rs10423928, A-allele) in the glucose-dependent insulinotropic polypeptide receptor gene (GIPR) is associated with decreased insulin secretion. Glucose-dependent insulinotropic polypeptide is secreted after food consumption and gipr knockout mice fed a high-fat diet are protected against obesity and disturbances in glucose homeostasis.

Objective:

Our objective was to examine the interactions between rs10423928 and macronutrients and fiber intakes on body mass index and type 2 diabetes risk.

Design, Setting, and Participants:

Among nondiabetic subjects in the Swedish population-based Malmö Diet and Cancer cohort (n = 24,840; 45–74 yr), 1541 diabetes cases were identified during 12 yr of follow-up. Dietary intakes were assessed using a diet history method.

Main Outcome Measure:

Incident type 2 diabetes was identified through registers.

Results:

There was no indication that dietary intakes significantly modify the association between GIPR genotype and body mass index (P interaction >0.08). We observed significant interactions between GIPR genotype and quintiles of carbohydrate (P = 0.0005) and fat intake (P = 0.0006) on incident type 2 diabetes. The TT-genotype carriers within the highest compared with the lowest carbohydrate quintile were at 23% (95% confidence interval = 5–39%) decreased type 2 diabetes risk. In contrast, AA-genotype carriers in the highest compared with the lowest fat quintile were at 69% (95% confidence interval = 29–86%) decreased risk.

Conclusions:

Our prospective, observational study indicates that the type 2 diabetes risk by dietary intake of carbohydrate and fat may be dependent on GIPR genotype. In line with results in gipr knockout mice, AA-genotype carriers consuming high-fat low-carbohydrate diets had reduced type 2 diabetes risk, whereas high-carbohydrate low-fat diets benefitted the two thirds of population homozygous for the T-allele.