Novel Risk Panel for CAD and All-Cause Mortality in Type 1 Diabetes

Abstract

Coronary artery disease (CAD) prevalence is increased and life expectancy is reduced by more than a decade in people with type 1 diabetes (T1D) compared to nondiabetics (non-DM), but traditional risk factors do not explain all of the increased risk. We examined whether three novel risk markers, high-sensitive cardiac troponin T (hs-cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and growth differentiation factor 15 (GDF-15), are elevated in T1D and predict CAD and mortality. 1,416 adults age 19-56 (652 T1D, 754 non-DM) were enrolled in the Coronary Artery Calcification in type 1 diabetes (CACTI) study from 2000-2002. We assessed CAD events (fatal or non-fatal myocardial infarction, coronary artery bypass graft, or angioplasty) with annual follow-up questionnaires. In-person visits occurred at 3, 6, and 12 years after baseline. Serum samples from the visit prior to a CAD event or death or from the last in-person visit were available for 1,389 participants and were assayed for hs-cTnT, NT-proBNP, and GDF-15 at the University of Maryland. Elevated marker levels were defined as those above the 95th percentile among non-DM participants. Biomarker levels were compared by T1D status in linear regression, and logistic regression was used to examine associations with CAD and all-cause mortality. Age- and sex-adjusted LSmeans ± SE for log hs-cTnT (2.0±0.02 vs. 1.6±0.02, p<0.0001), log NT-proBNP (3.8±0.04 vs. 3.5±0.03, p#x003C;0.0001), and log GDF-15 (6.5±0.02 vs. 6.2±0.02, p#x003C;0.0001) were significantly higher in T1D than non-DM participants. Over the follow-up period, there were 72 CAD events (53 T1D, 19 non-DM) and 76 deaths (58 T1D, 18 non-DM). Having elevated levels of all 3 vs. none of the markers was a significant predictor of both CAD (OR [95% CI] 6.4 [2.0-20.7]) and all-cause mortality (OR [95% CI] 10.7 [3.3-35.4]), independent of age, sex, renal function and T1D status. A panel of novel markers, hs-cTnT, NT-proBNP, and GDF-15, are elevated in T1D and may help identify those at risk for CAD events and mortality. Disclosure A. Keshawarz: None. R.M. Sippl: None. H. Rebuck: None. S. Donald: None. S.Y. Huang: None. R.H. Christenson: Consultant; Self; Roche Diagnostics Corporation, Siemens, Becton, Dickinson and Company. J.K. Snell-Bergeon: Stock/Shareholder; Self; Abbott. Research Support; Self; Roche Diagnostics Corporation.