Lifestyle and Metformin Ameliorate Insulin Sensitivity Independently of the Genetic Burden of Established Insulin Resistance Variants in Diabetes Prevention Program Participants.

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  • Additional Information
    • Corporate Authors:
      Diabetes Prevention Program Research Group
    • Source:
      Publisher: American Diabetes Association Country of Publication: United States NLM ID: 0372763 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1939-327X (Electronic) Linking ISSN: 00121797 NLM ISO Abbreviation: Diabetes Subsets: MEDLINE
    • Publication Information:
      Publication: Alexandria, VA : American Diabetes Association
      Original Publication: [New York, American Diabetes Association]
    • Subject Terms:
      Risk Reduction Behavior*; Diabetes Mellitus, Type 2/*prevention & control ; Hypoglycemic Agents/*therapeutic use ; Insulin Resistance/*genetics ; Metformin/*therapeutic use; Adult ; Diabetes Mellitus, Type 2/genetics ; Female ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; United States
    • Abstract:
      Large genome-wide association studies of glycemic traits have identified genetics variants that are associated with insulin resistance (IR) in the general population. It is unknown whether people with genetic enrichment for these IR variants respond differently to interventions that aim to improve insulin sensitivity. We built a genetic risk score (GRS) based on 17 established IR variants and effect sizes (weighted IR-GRS) in 2,713 participants of the Diabetes Prevention Program (DPP) with genetic consent. We tested associations between the weighted IR-GRS and insulin sensitivity index (ISI) at baseline in all participants, and with change in ISI over 1 year of follow-up in the DPP intervention (metformin and lifestyle) and control (placebo) arms. All models were adjusted for age, sex, ethnicity, and waist circumference at baseline (plus baseline ISI for 1-year ISI change models). A higher IR-GRS was associated with lower baseline ISI (β = -0.754 [SE = 0.229] log-ISI per unit, P = 0.001 in fully adjusted models). There was no differential effect of treatment for the association between the IR-GRS on the change in ISI; higher IR-GRS was associated with an attenuation in ISI improvement over 1 year (β = -0.520 [SE = 0.233], P = 0.03 in fully adjusted models; all treatment arms). Lifestyle intervention and metformin treatment improved the ISI, regardless of the genetic burden of IR variants.
      (© 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)
    • References:
      Diabetes. 2010 May;59(5):1266-75. (PMID: 20185807)
      Diabetes. 2010 Oct;59(10):2672-81. (PMID: 20682687)
      Diabetes. 2011 Apr;60(4):1340-8. (PMID: 21378175)
      Nat Genet. 2012 Jun;44(6):659-69. (PMID: 22581228)
      Nat Genet. 2012 Sep;44(9):991-1005. (PMID: 22885924)
      Nat Rev Endocrinol. 2014 Apr;10(4):198-205. (PMID: 24535206)
      Diabetes. 2014 Jun;63(6):2158-71. (PMID: 24296717)
      Diabetes. 2014 Jun;63(6):2172-82. (PMID: 24520119)
      Diabetes Care. 2000 Nov;23(11):1619-29. (PMID: 11092283)
      N Engl J Med. 2002 Feb 7;346(6):393-403. (PMID: 11832527)
      Diabetologia. 2003 Jan;46(1):3-19. (PMID: 12637977)
      Diabetes. 2003 Oct;52(10):2532-8. (PMID: 14514637)
      Diabetologia. 1985 Jul;28(7):412-9. (PMID: 3899825)
      Diabetologia. 1994 Sep;37(9):889-96. (PMID: 7806018)
      Diabetes Care. 1999 Apr;22(4):623-34. (PMID: 10189543)
      Diabetes. 2005 Aug;54(8):2404-14. (PMID: 16046308)
      Obesity (Silver Spring). 2006 Nov;14(11):2107-17. (PMID: 17135629)
      Diabetologia. 2008 Jul;51(7):1100-10. (PMID: 18504548)
      Diabetes Care. 2009 Feb;32(2):335-41. (PMID: 18957530)
      Nat Genet. 2010 Feb;42(2):105-16. (PMID: 20081858)
    • Grant Information:
      U01 DK048412 United States DK NIDDK NIH HHS; U01 DK048375 United States DK NIDDK NIH HHS; U01 DK048434 United States DK NIDDK NIH HHS; U01 DK048413 United States DK NIDDK NIH HHS; P30 DK079637 United States DK NIDDK NIH HHS; U01 DK048339 United States DK NIDDK NIH HHS; U01 DK048411 United States DK NIDDK NIH HHS; U01 DK048468 United States DK NIDDK NIH HHS; U01 DK048387 United States DK NIDDK NIH HHS; U01 DK048404 United States DK NIDDK NIH HHS; DK-48489 United States DK NIDDK NIH HHS; U01 DK048407 United States DK NIDDK NIH HHS; U01 DK048437 United States DK NIDDK NIH HHS; U01 DK048406 United States DK NIDDK NIH HHS; R01 DK072041 United States DK NIDDK NIH HHS; R01 DK078907 United States DK NIDDK NIH HHS; P30 DK097512 United States DK NIDDK NIH HHS; U01 DK048397 United States DK NIDDK NIH HHS; U01 DK048381 United States DK NIDDK NIH HHS; U01 DK048514 United States DK NIDDK NIH HHS; U01 DK048485 United States DK NIDDK NIH HHS; U01 DK048380 United States DK NIDDK NIH HHS; U01 DK048400 United States DK NIDDK NIH HHS; U01 DK048489 United States DK NIDDK NIH HHS; U01 DK048349 United States DK NIDDK NIH HHS; U01 DK048377 United States DK NIDDK NIH HHS; P30 DK017047 United States DK NIDDK NIH HHS
    • Accession Number:
      0 (Hypoglycemic Agents)
      9100L32L2N (Metformin)
    • Publication Date:
      Date Created: 20151104 Date Completed: 20160601 Latest Revision: 20220409
    • Publication Date:
      20240628
    • Accession Number:
      PMC4747453
    • Accession Number:
      10.2337/db15-0950
    • Accession Number:
      26525880