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

被引:16
作者
Sullivan, Shannon D. [1 ]
Jablonski, Kathleen A. [2 ]
Florez, Jose C. [3 ,4 ,5 ,6 ]
Dabelea, Dana [7 ]
Franks, Paul W. [8 ,9 ,10 ]
Dagogo-Jack, Sam [11 ]
Kim, Catherine [12 ,13 ]
Knowler, William C. [14 ]
Christophi, Costas A. [2 ]
Ratner, Robert [15 ]
机构
[1] MedStar Washington Hosp Ctr, Dept Med, Endocrine Div, Washington, DC USA
[2] George Washington Univ, Biostat Ctr, Rockville, MD USA
[3] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA
[4] Massachusetts Gen Hosp, Dept Med, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA
[5] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA
[6] Harvard Univ, Sch Med, Dept Med, Boston, MA USA
[7] Colorado Sch Publ Hlth, Dept Epidemiol, Aurora, CO USA
[8] Lund Univ, Skane Univ Hosp, Dept Clin Sci, Genet & Mol Epidemiol Unit,Diabet Ctr, Malmo, Sweden
[9] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
[10] Umea Univ, Dept Publ Hlth & Clin Med, Umea, Sweden
[11] Univ Tennessee, Hlth Sci Ctr, Div Endocrinol Diabet & Metab, Memphis, TN USA
[12] Univ Michigan, Dept Med, Ann Arbor, MI 48109 USA
[13] Univ Michigan, Dept Obstet & Gynecol, Ann Arbor, MI 48109 USA
[14] NIDDK, Phoenix, AZ USA
[15] Amer Diabet Assoc, Alexandria, VA USA
基金
瑞典研究理事会; 美国国家卫生研究院;
关键词
D O I
10.2337/dc13-0700
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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.
引用
收藏
页码:909 / 911
页数:3
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