title: 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.
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 β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM. RESULTS β-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 β-cell dysfunction.
authors.affiliation: Corresponding author: Shannon D. Sullivan, dppmail@bsc.gwu.edu.
authors.forename: Shannon D
authors.initials: SD
authors.lastname: Sullivan
authors.forename: Kathleen A
authors.initials: KA
authors.lastname: Jablonski
authors.forename: Jose C
authors.initials: JC
authors.lastname: Florez
authors.forename: Dana
authors.initials: D
authors.lastname: Dabelea
authors.forename: Paul W
authors.initials: PW
authors.lastname: Franks
authors.forename: Sam
authors.initials: S
authors.lastname: Dagogo-Jack
authors.forename: Catherine
authors.initials: C
authors.lastname: Kim
authors.forename: William C
authors.initials: WC
authors.lastname: Knowler
authors.forename: Costas A
authors.initials: CA
authors.lastname: Christophi
authors.forename: Robert
authors.initials: R
authors.lastname: Ratner
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000235:genetics*; D016640:Diabetes, Gestational / Q000188:drug therapy* / Q000453:epidemiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007515:Islets of Langerhans / Q000503:physiopathology; D008019:Life Style; D008687:Metformin / Q000627:therapeutic use*; D011236:Prediabetic State / Q000188:drug therapy* / Q000453:epidemiology*; D011247:Pregnancy; D012307:Risk Factors
chemical_list: D007004:Hypoglycemic Agents; D008687:Metformin