Genetic risk of progression to type 2 diabetes and response to intensive lifestyle or metformin in prediabetic women with and without a history of gestational diabetes mellitus

  • S.D. S
  • K.A. J
  • J.C. F
 et al. 
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Abstract

OBJECTIVE: The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births. RESEARCH DESIGN AND METHODS: We asked if genetic variability could account for these differences by comparing beta-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM. RESULTS: beta-Cell function was reduced in women with GDM. The GRS was positively associated with a history of GDM; however, the GRS did not predict progression to diabetes or modulate response to intervention. CONCLUSIONS: These data suggest that a diabetes-associated GRS is associated with development of GDM and may characterize women at risk for development of diabetes due to beta-cell dysfunction. © 2014 by the American Diabetes Association.

Author-supplied keywords

  • *genetic risk
  • *impaired glucose tolerance/th [Therapy]
  • *lifestyle modification
  • *metformin/ct [Clinical Trial]
  • *metformin/dt [Drug Therapy]
  • *non insulin dependent diabetes mellitus/co [Compl
  • *non insulin dependent diabetes mellitus/th [Thera
  • GCKR gene
  • IRS1 gene
  • KLF14 gene
  • PPARG gene
  • adult
  • article
  • clinical trial (topic)
  • female
  • gene
  • gene locus
  • genetic association
  • genetic variability
  • human
  • insulin receptor substrate 1/ec [Endogenous Compou
  • insulin sensitivity
  • kruppel like factor/ec [Endogenous Compound]
  • major clinical study
  • medical history
  • pancreas islet beta cell
  • pancreas islet cell function
  • peroxisome proliferator activated receptor gamma/e
  • pharmacogenetics
  • placebo
  • pregnancy diabetes mellitus/dt [Drug Therapy]
  • risk assessment
  • risk factor
  • scoring system
  • single nucleotide polymorphism
  • treatment outcome

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Authors

  • Sullivan S.D.

  • Jablonski K.A.

  • Florez J.C.

  • Dabelea D.

  • Franks P.W.

  • Dagogo-Jack S.

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