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Variation in maturi...
Variation in maturity-onset diabetes of the young genes influence response to interventions for diabetes prevention
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- Billings, Liana K. (författare)
- Harvard Medical School,Massachusetts General Hospital,NorthShore University HealthSystem
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- Jablonski, Kathleen A (författare)
- George Washington University
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- Warner, A. Sofia (författare)
- Massachusetts General Hospital
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- Cheng, Yu Chien (författare)
- NorthShore University HealthSystem,University of Chicago
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- McAteer, Jarred B. (författare)
- Massachusetts General Hospital
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- Tipton, Laura (författare)
- George Washington University
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Shuldiner, Alan R. (författare)
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- Ehrmann, David A (författare)
- University of Chicago
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- Manning, Alisa K. (författare)
- Broad Institute,Harvard Medical School,Massachusetts General Hospital
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- Dabelea, Dana (författare)
- Colorado School of Public Health
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- Franks, Paul W. (författare)
- Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
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- Kahn, Steven E (författare)
- University of Washington
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- Pollin, Toni I (författare)
- University of Maryland, Baltimore
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- Knowler, William C (författare)
- National Institute of Diabetes and Digestive and Kidney Diseases
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- Altshuler, David (författare)
- Harvard Medical School,Broad Institute
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- Florez, Jose C. (författare)
- Massachusetts General Hospital,Harvard Medical School,George Washington University,Broad Institute
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(creator_code:org_t)
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- 2017-04-27
- 2017
- Engelska 12 s.
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Ingår i: Journal of Clinical Endocrinology and Metabolism. - : The Endocrine Society. - 0021-972X .- 1945-7197. ; 102:8, s. 2678-2689
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http://dx.doi.org/10... (free)
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https://academic.oup...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
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- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
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Billings, Liana ...
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Jablonski, Kathl ...
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Warner, A. Sofia
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Cheng, Yu Chien
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McAteer, Jarred ...
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Tipton, Laura
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visa fler...
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Shuldiner, Alan ...
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Ehrmann, David A
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Manning, Alisa K ...
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Dabelea, Dana
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Franks, Paul W.
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Kahn, Steven E
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Pollin, Toni I
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Knowler, William ...
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Altshuler, David
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Florez, Jose C.
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visa färre...
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