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- Title
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 Malmo Diet and Cancer cohort.
- Authors
Sonestedt E; Lyssenko V; Ericson U; Gullberg B; Wirfält E; Groop L; Orho-Melander M; Sonestedt, Emily; Lyssenko, Valeriya; Ericson, Ulrika; Gullberg, Bo; Wirfält, Elisabet; Groop, Leif; Orho-Melander, Marju
- Abstract
<bold>Context: </bold>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.<bold>Objective: </bold>Our objective was to examine the interactions between rs10423928 and macronutrients and fiber intakes on body mass index and type 2 diabetes risk.<bold>Design, Setting, and Participants: </bold>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.<bold>Main Outcome Measure: </bold>Incident type 2 diabetes was identified through registers.<bold>Results: </bold>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.<bold>Conclusions: </bold>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.
- Publication
Journal of Clinical Endocrinology & Metabolism, 2012, Vol 97, Issue 5, pE810
- ISSN
0021-972X
- Publication type
journal article
- DOI
10.1210/jc.2011-2444