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  • Billings, Liana K.Harvard Medical School,Massachusetts General Hospital,NorthShore University HealthSystem (author)

Variation in maturity-onset diabetes of the young genes influence response to interventions for diabetes prevention

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-04-27
  • The Endocrine Society,2017
  • 12 s.

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  • LIBRIS-ID:oai:lup.lub.lu.se:7fd08be3-041e-4222-96c7-8638e41333f9
  • https://lup.lub.lu.se/record/7fd08be3-041e-4222-96c7-8638e41333f9URI
  • https://doi.org/10.1210/jc.2016-3429DOI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:art swepub-publicationtype
  • Subject category:ref swepub-contenttype

Notes

  • Context: Variation in genes that cause maturity-onset diabetes of the young (MODY) has been associated with diabetes incidence and glycemic traits. Objectives: This study aimed to determine whether genetic variation in MODY genes leads to differential responses to insulin-sensitizing interventions. Design and Setting: This was a secondary analysis of a multicenter, randomized clinical trial, the Diabetes Prevention Program (DPP), involving 27 US academic institutions. We genotyped 22 missense and 221 common variants in the MODY-causing genes in the participants in the DPP. Participants and Interventions: The study included 2806 genotyped DPP participants randomized to receive intensive lifestyle intervention (n = 935), metformin (n = 927), or placebo (n = 944). Main Outcome Measures: Association of MODY genetic variants with diabetes incidence at a median of 3 years and measures of 1-year β-Cell function, insulinogenic index, and oral disposition index. Analyses were stratified by treatment group for significant single-nucleotide polymorphism 3 treatment interaction (Pint, 0.05). Sequence kernel association tests examined the association between an aggregate of rare missense variants and insulinogenic traits. Results: After 1 year, the minor allele of rs3212185 (HNF4A) was associated with improved β-Cell function in the metformin and lifestyle groups but not the placebo group; the minor allele of rs6719578 (NEUROD1) was associated with an increase in insulin secretion in the metformin group but not in the placebo and lifestyle groups. Conclusions: These results provide evidence that genetic variation among MODY genes may influence response to insulin-sensitizing interventions.

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  • Jablonski, Kathleen AGeorge Washington University (author)
  • Warner, A. SofiaMassachusetts General Hospital (author)
  • Cheng, Yu ChienNorthShore University HealthSystem,University of Chicago (author)
  • McAteer, Jarred B.Massachusetts General Hospital (author)
  • Tipton, LauraGeorge Washington University (author)
  • Shuldiner, Alan R. (author)
  • Ehrmann, David AUniversity of Chicago (author)
  • Manning, Alisa K.Broad Institute,Harvard Medical School,Massachusetts General Hospital (author)
  • Dabelea, DanaColorado School of Public Health (author)
  • Franks, Paul W.Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups(Swepub:lu)med-plf (author)
  • Kahn, Steven EUniversity of Washington (author)
  • Pollin, Toni IUniversity of Maryland, Baltimore (author)
  • Knowler, William CNational Institute of Diabetes and Digestive and Kidney Diseases (author)
  • Altshuler, DavidHarvard Medical School,Broad Institute (author)
  • Florez, Jose C.Massachusetts General Hospital,Harvard Medical School,George Washington University,Broad Institute (author)
  • Harvard Medical SchoolMassachusetts General Hospital (creator_code:org_t)
  • Diabetes Prevention Program Research Group

Related titles

  • In:Journal of Clinical Endocrinology and Metabolism: The Endocrine Society102:8, s. 2678-26890021-972X1945-7197

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