Abstract
BackgroundMany 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.MethodsAssociations 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.ResultsThe 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.ConclusionsThis analysis highlights important demographic and clinical factors, notably CAC and albuminuria, which predict mortality in the general population of patients with T2D.Electronic supplementary materialThe online version of this article (doi:10.1186/s13098-015-0055-y) contains supplementary material, which is available to authorized users.
Highlights
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 CVD mortality model selected from the full sample included age, sex, calcified plaque (CAC), urine albumin: creatinine ratio (UACR), triglycerides, and history of CVD (Table 3)
For medication use Hazards ratios (HRs), the HRs are for risk of mortality among those individuals using the given medication class
Summary
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) is an ongoing familybased cohort study investigating the epidemiology and genetics of cardiovascular disease (CVD) in a population-based sample. Prior analyses in this type 2 diabetes (T2D)-enriched cohort [1] have individually examined contributors to allcause and CVD mortality. Fewer studies have attempted to evaluate the best predictors of all-cause and CVD mortality in T2D [11,12,13,14]. We performed a comprehensive analysis of which factors were the strongest independent predictors of all-cause and CVD mortality using model selection
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