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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.

Sonestedt, Emily LU ; Lyssenko, Valeriya LU ; Ericson, Ulrika LU ; Gullberg, Bo LU ; Wirfält, Elisabet LU ; Groop, Leif LU and Orho-Melander, Marju LU (2012) In The Journal of clinical endocrinology and metabolism 97(5). p.810-818
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
The Journal of clinical endocrinology and metabolism
volume
97
issue
5
pages
810 - 818
publisher
The Endocrine Society
external identifiers
  • wos:000303915900018
  • pmid:22399504
  • scopus:84860733554
ISSN
1945-7197
DOI
10.1210/jc.2011-2444
language
English
LU publication?
yes
id
4663b3ed-5ae6-4770-8c3b-395b12a7d31c (old id 2432153)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22399504?dopt=Abstract
date added to LUP
2012-04-03 09:30:11
date last changed
2017-10-22 03:58:31
@article{4663b3ed-5ae6-4770-8c3b-395b12a7d31c,
  abstract     = {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.<br/><br>
<br/><br>
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.<br/><br>
<br/><br>
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 &gt;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.<br/><br>
<br/><br>
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.},
  author       = {Sonestedt, Emily and Lyssenko, Valeriya and Ericson, Ulrika and Gullberg, Bo and Wirfält, Elisabet and Groop, Leif and Orho-Melander, Marju},
  issn         = {1945-7197},
  language     = {eng},
  number       = {5},
  pages        = {810--818},
  publisher    = {The Endocrine Society},
  series       = {The Journal of clinical endocrinology and metabolism},
  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.},
  url          = {http://dx.doi.org/10.1210/jc.2011-2444},
  volume       = {97},
  year         = {2012},
}