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.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors.affiliation: Department of Clinical Sciences, Malmö, Lund University, Clinical Research Centre, Building 60 Floor 13, Skåne University Hospital, Malmö, Entrance 72, Malmö SE-205 02, Sweden. emily.sonestedt@med.lu.se
authors.forename: Emily
authors.initials: E
authors.lastname: Sonestedt
authors.forename: Valeriya
authors.initials: V
authors.lastname: Lyssenko
authors.forename: Ulrika
authors.initials: U
authors.lastname: Ericson
authors.forename: Bo
authors.initials: B
authors.lastname: Gullberg
authors.forename: Elisabet
authors.initials: E
authors.lastname: Wirfält
authors.forename: Leif
authors.initials: L
authors.lastname: Groop
authors.forename: Marju
authors.initials: M
authors.lastname: Orho-Melander
mesh_terms: D000328:Adult; D000483:Alleles; D001823:Body Composition / Q000235:genetics; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D004032:Diet; D004040:Dietary Carbohydrates; D004041:Dietary Fats; D005260:Female; D005500:Follow-Up Studies; D059647:Gene-Environment Interaction; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics; D011446:Prospective Studies; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics*
chemical_list: D004040:Dietary Carbohydrates; D004041:Dietary Fats; D011964:Receptors, Gastrointestinal Hormone; C041086:gastric inhibitory polypeptide receptor