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Photo: KG Pressfoto

Marju Orho-Melander


Photo: KG Pressfoto

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.


  • Emily Sonestedt
  • Valeriya Lyssenko
  • Ulrika Ericson
  • Bo Gullberg
  • Elisabet Wirfält
  • Leif Groop
  • Marju Orho-Melander

Summary, in English

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.


  • Nutrition Epidemiology
  • Diabetes - Cardiovascular Disease
  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • EpiHealth: Epidemiology for Health

Publishing year







The Journal of clinical endocrinology and metabolism





Document type

Journal article


Oxford University Press


  • Endocrinology and Diabetes



Research group

  • Nutrition Epidemiology
  • Diabetes - Cardiovascular Disease
  • Genomics, Diabetes and Endocrinology


  • ISSN: 1945-7197