title: Predictors of all-cause and cardiovascular disease mortality in type 2 diabetes: Diabetes Heart Study.
abstract: BACKGROUND
  Many studies evaluated the best predictors for cardiovascular disease (CVD) events in individuals with type 2 diabetes (T2D), but few studies examined the factors most strongly associated with mortality in T2D. The Diabetes Heart Study (DHS), an intensively phenotyped family-based cohort enriched for T2D, provided an opportunity to address this question.
  
  
  METHODS
  Associations with mortality were examined in 1022 European Americans affected by T2D from 476 DHS families. All-cause mortality was 31.2 % over an average 9.6 years of follow-up. Cox proportional hazards models with sandwich-based variance estimation were used to evaluate associations between all-cause and CVD mortality and 24 demographic and clinical factors, including coronary artery calcified plaque (CAC), carotid artery intima-media thickness, medications, body mass index, waist hip ratio, lipids, blood pressure, kidney function, QT interval, educational attainment, and glycemic control. Nominally significant factors (p < 0.25) from univariate analyses were included in model selection (backward elimination, forward selection, and stepwise selection). Age and sex were included in all models.
  
  
  RESULTS
  The all-cause mortality model selected from the full DHS sample included age, sex, CAC, urine albumin: creatinine ratio (UACR), insulin use, current smoking, and educational attainment. The CVD mortality model selected from the full sample included age, sex, CAC, UACR, triglycerides, and history of CVD events. Beyond age, the most significant associations for both mortality models were CAC (2.03 × 10(-4) ≤ p ≤ 0.001) and UACR (1.99 × 10(-8) ≤ p ≤ 2.23 × 10(-8)). To confirm the validity of the main predictors identified with model selection using the full sample, a two-fold cross-validation approach was used, and similar results were observed.
  
  
  CONCLUSIONS
  This analysis highlights important demographic and clinical factors, notably CAC and albuminuria, which predict mortality in the general population of patients with T2D.
authors.affiliation: Molecular Genetics and Genomics Program, Wake Forest School of Medicine, Winston-Salem, NC USA ; Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC USA ; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Raffield
authors.affiliation: Department of Biostatistical Sciences, Wake Forest School of Medicine, Winston-Salem, NC USA.
authors.forename: Fang-Chi
authors.initials: FC
authors.lastname: Hsu
authors.affiliation: Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC USA ; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC USA ; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC USA.
authors.forename: Amanda J
authors.initials: AJ
authors.lastname: Cox
authors.affiliation: Department of Radiology, Vanderbilt University Medical Center, Nashville, TN USA.
authors.forename: J Jeffrey
authors.initials: JJ
authors.lastname: Carr
authors.affiliation: Department of Internal Medicine - Nephrology, Wake Forest School of Medicine, Winston-Salem, NC USA.
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.affiliation: Center for Human Genomics, Wake Forest School of Medicine, Winston-Salem, NC USA ; Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC USA ; Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, NC USA ; Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Medical Center Boulevard, Winston-Salem, NC 27157 USA.
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
keywords: Coronary artery calcified plaque; Mortality; Type 2 diabetes; Urine albumin:creatinine ratio