The C allele of ATM rs11212617 does not associate with metformin response in the Diabetes Prevention Program

Diabetes Care. 2012 Sep;35(9):1864-7. doi: 10.2337/dc11-2301. Epub 2012 Jun 29.

Abstract

Objective: The C allele at the rs11212617 polymorphism in the ataxia-telangiectasia-mutated (ATM) gene has been associated with greater clinical response to metformin in people with type 2 diabetes. We tested whether this variant modified the effect of metformin in the Diabetes Prevention Program (DPP), in which metformin reduced diabetes incidence by 31% in volunteers with impaired glucose tolerance.

Research design and methods: We genotyped rs11212617 in 2,994 DPP participants and analyzed its effects on diabetes incidence and related traits.

Results: Contrary to expectations, C carriers enjoyed no preventive advantage on metformin; their hazard ratio, compared with A carriers, was 1.17 ([95% CI 0.96-1.42], P = 0.13) under metformin. There were no significant differences by genotype in metformin's effects on insulin sensitivity, fasting glucose, glycated hemoglobin, or disposition index.

Conclusions: The reported association of rs11212617 with metformin response was not confirmed for diabetes prevention or for effects on relevant physiologic parameters in the DPP.

Trial registration: ClinicalTrials.gov NCT00004992.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ataxia Telangiectasia Mutated Proteins
  • Blood Glucose / metabolism
  • Cell Cycle Proteins / genetics*
  • DNA-Binding Proteins / genetics*
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / genetics
  • Diabetes Mellitus / metabolism
  • Diabetes Mellitus / prevention & control*
  • Fasting / blood
  • Female
  • Genotype
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / therapeutic use*
  • Male
  • Metformin / therapeutic use*
  • Middle Aged
  • Polymorphism, Genetic / genetics*
  • Protein-Serine-Threonine Kinases / genetics*
  • Tumor Suppressor Proteins / genetics*

Substances

  • Blood Glucose
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Tumor Suppressor Proteins
  • Metformin
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases

Associated data

  • ClinicalTrials.gov/NCT00004992