TY - JOUR
T1 - The C allele of ATM rs11212617 does not associate with metformin response in the diabetes prevention program
AU - Florez, Jose C.
AU - Barrett-Connor, Elizabeth
AU - Jablonski, Kathleen A.
AU - Knowler, William C.
AU - Taylor, Andrew
AU - Shuldiner, Alan R.
AU - Mather, Kieren
AU - Pollin, Toni I.
AU - Horton, Edward
AU - White, Neil H.
PY - 2012/9
Y1 - 2012/9
N2 - 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, comparedwith 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.
AB - 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, comparedwith 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.
UR - http://www.scopus.com/inward/record.url?scp=84865457823&partnerID=8YFLogxK
U2 - 10.2337/dc11-2301
DO - 10.2337/dc11-2301
M3 - Article
C2 - 22751958
AN - SCOPUS:84865457823
SN - 0149-5992
VL - 35
SP - 1864
EP - 1867
JO - Diabetes care
JF - Diabetes care
IS - 9
ER -