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Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes.

ABSTRACT: BACKGROUND:TCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence. RESULTS:We included 26,905 individuals without diabetes from the Malmö Diet and Cancer Study cohort. Diet data was collected at baseline using a food frequency questionnaire, a 7-day food record, and an interview. Altogether, 51 gene loci were analyzed for putative links to WNT signaling. Over a mean follow-up period of 14.7 years, 3132 incident cases of type 2 diabetes were recorded. Seven genes (nine single nucleotide polymorphisms (SNPs)) were annotated as involved in WNT signaling including TCF7L2 (rs7903146 and rs12255372), HHEX (rs1111875), HNF1A (rs7957197), NOTCH2 (rs10923931), TLE4 (rs13292136), ZBED3 (rs4457053), and PPARG (rs1801282 and rs13081389). SNPs in TCF7L2, NOTCH2, and ZBED3 showed significant interactions with fiber intake on type 2 diabetes incidence (P interaction?=?0.034, 0.005, 0.017, and 0.002, respectively). The magnitude of the association between the TCF7L2 risk allele and incident type 2 diabetes increased from the lowest to the highest quintiles of fiber intake. Higher fiber associated with lower type 2 diabetes risk only among risk allele carriers of the NOTCH2 variant and homozygotes of the risk allele of the ZBED3 variant. CONCLUSIONS:Our results suggest that several type 2 diabetes susceptibility SNPs in genes involved in WNT signaling may interact with dietary fiber intake on type 2 diabetes incidence.

SUBMITTER: Hindy G

PROVIDER: S-EPMC4968454 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes.

Hindy George G Mollet Inês G IG Rukh Gull G Ericson Ulrika U Orho-Melander Marju M

Genes & nutrition 20160321

<h4>Background</h4>TCF7L2 is a central transcription factor in the canonical wingless-type MMTV integration site (WNT) signaling pathway, and genetic variants in TCF7L2 have been found to interact with dietary fiber intake on type 2 diabetes risk. Here, we investigate whether other type 2 diabetes genes could be involved in the WNT signaling pathway and whether variants in such genes might interact with dietary fiber on type 2 diabetes incidence.<h4>Results</h4>We included 26,905 individuals wit ...[more]

PMID: 27551309

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Project description:ImportanceDietary proteins, such as gluten, have been suggested as triggers of the disease process in type 1 diabetes (T1D).ObjectiveTo study the associations of cereal, gluten, and dietary fiber intake with the development of islet autoimmunity (IA) and T1D.Design, setting, and participantsThe prospective birth cohort Finnish Type 1 Diabetes Prediction and Prevention Study recruited children with genetic susceptibility to type 1 diabetes from September 1996 to September 2004 from 2 university hospitals in Finland and followed up every 3 to 12 months up to 6 years for diet, islet autoantibodies, and T1D. Altogether 6081 infants (78% of those invited) participated in the study. Dietary data were available for 5714 children (94.0%) and dietary and IA data were available for 5545 children (91.2%), of whom 3762 (68%) had data on islet autoantibodies up to age 6 years. Information on T1D was available for all children. Data were analyzed in 2018 and end point data were updated in 2015.ExposuresEach child's intake of cereals, gluten, and dietary fiber was calculated from repeated 3-day food records up to 6 years.Main outcomes and measuresIslet autoimmunity was defined as repeated positivity for islet cell antibodies and at least 1 biochemical autoantibody of 3 analyzed, or T1D. Data on the diagnosis of T1D were obtained from Finnish Pediatric Diabetes Register.ResultsOf 5545 children (2950 boys [53.2%]), 246 (4.4%) developed IA and of 5714 children (3033 boys [53.1%]), 90 (1.6%) developed T1D during the 6-year follow-up. Based on joint models, the intake of oats (hazard ratio [HR], 1.08; 95% CI, 1.03-1.13), wheat (HR, 1.09; 95% CI, 1.03-1.15), rye (HR, 1.13; 95% CI, 1.03-1.23), gluten-containing cereals (HR, 1.07; 95% CI, 1.03-1.11), gluten without avenin from oats (HR, 2.23; 95% CI, 1.40-3.57), gluten with avenin (HR, 2.06; 95% CI, 1.45-2.92), and dietary fiber (HR, 1.41; 95% CI, 1.10-1.81) was associated with the risk of developing IA (HRs for 1 g/MJ increase in intake). The intake of oats (HR, 1.10; 95% CI, 1.00-1.21) and rye (HR, 1.20; 95% CI, 1.03-1.41) was associated with the risk of developing T1D. After multiple testing correction, the associations with IA remained statistically significant.Conclusions and relevanceA high intake of oats, gluten-containing cereals, gluten, and dietary fiber was associated with an increased risk of IA. Further studies are needed to confirm or rule out the findings and study potential mechanisms.

Project description:Diabetes and obesity seem to be partly overlapping risk factors for the development of obesity-related cancer (mainly breast, prostate and colorectal cancer) in patients with type 2 diabetes (T2DM). In the general population, women have a lower risk for obesity-related cancer compared to men. Previous studies involving cardiovascular disease have shown that T2DM eliminates a female advantage of lower CVD risk in the general population compared to men. It is unclear whether the same could be true for obesity-related cancer. This study aimed to this investigate obesity-related cancer incidence in women and men known with T2DM as compared to the Dutch general population.This study included 69,583 patients with T2DM selected from a prospective primary care cohort, which was linked to the Dutch National Cancer Registry to obtain cancer specific data. Obesity-related cancers included liver, kidney, colorectal, gallbladder, pancreas, ovarian, endometrial, advanced prostate cancer, post-menopausal breast cancer and oesophageal adenocarcinoma. Primary outcome was sex-stratified, age and year of cancer diagnosis adjusted standardized incidence ratios (SIRs) for three time periods: 5 years before, the year after diagnosis and the next 4 years after T2DM diagnosis. The Dutch general population was used as reference group.Women with T2DM were at an increased risk for obesity-related cancer compared to women in the general population already 5 years before diabetes diagnosis (SIR 1.77; 95%CI: 1.63-1.91). In both men and women, there was a peak in obesity-related cancer incidence following diabetes diagnosis (SIR: 1.38; 95%CI 1.11-1.64 and SIR: 2.21; 95%CI 1.94-2.30, respectively). From the second to the fifth year after diabetes diagnosis the obesity-related cancer incidence was higher in women compared to women in the general population (SIR: 2.12; 95%CI 1.94-2.30).Women with T2DM seem to have a substantially higher obesity-related cancer risk. As opposed to men, in women this risk was already increased years before diabetes diagnosis. These results could imply that a relative advantage of women in the general population with regard to cancer risk is lost in women with T2DM.

Dataset Information

Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes.

Publications

Several type 2 diabetes-associated variants in genes annotated to WNT signaling interact with dietary fiber in relation to incidence of type 2 diabetes.

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