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OBJECTIVE High-sensitivity cardiac troponin-T (hs-cTnT) and N-terminal prohormone of B-type natriuretic peptide (NT-proBNP), biomarkers of cardiovascular disease (CVD) and heart failure, respectively, have not been widely studied in type 1 diabetes (T1D). We evaluated whether their assessment in T1D enhances the prediction of CVD and major adverse cardiovascular events (MACE). RESEARCH DESIGN AND METHODS hs-cTnT and NT-proBNP were analyzed on the Roche Cobas E601 using the first available stored specimen (n = 581; mean age 29 years and diabetes duration 21 years). CVD was defined as CVD death, myocardial infarction, coronary revascularization, angina, ischemia, or stroke, and MACE as CVD death, myocardial infarction, or stroke. RESULTS Median hs-cTnT (5.0 ng/L; interquartile range CONCLUSIONS Sex differences were observed in the concentration and predictive ability of hs-cTnT and NT-proBNP in T1D. Overall, their addition to traditional risk factor models increased the area under the curve for neither CVD nor MACE.

Objective: High-sensitivity cardiac Troponin-T (hs-cTnT) and N-terminal pro B-Type natriuretic peptide (NT-proBNP), biomarkers of cardiovascular disease (CVD) and heart failure, respectively, have not been widely studied in type 1 diabetes (T1D). We evaluated whether their assessment in T1D enhances the prediction of CVD and major atherosclerotic cardiovascular events (MACE). Research Design and Methods: hs-cTnT and NT-proBNP were analyzed on the Roche Cobas E601 utilizing the first available stored specimen (n=581; mean age 29 and duration 21 years). CVD was defined as CVD death, myocardial infarction, coronary revascularization, angina, ischemia, or stroke and MACE as CVD death, myocardial infarction, or stroke. Results: Median hs-cTnT (5.0 ng/L, IQR: Conclusions: Sex differences were observed in the concentration and predictive ability of hs-cTnT and NT-proBNP in T1D. Overall, their addition to traditional risk factor models increased the area under the curve for neither CVD nor MACE.

High-sensitivity troponin T (hsTnT), a marker of CVD, and N-Terminal pro B-Type Natriuretic Peptide (NT-proBNP), a marker of heart failure, have not been widely studied in type 1 diabetes. We thus assessed the ability of these markers to independently predict CVD and MACE in a cohort with childhood-onset T1D (n=583, mean age 29 and duration 21 years) during a median follow-up of 21 years. CVD was defined as CVD death, myocardial infarction, revascularization, angina, or ischemia, and MACE as CVD death, myocardial infarction, or stroke. hsTnT and NT-proBNP were assessed with electrochemiluminescence immunoassays. Median hsTnT was 5.0 ng/L (IQR: 2.0, 10.0) and median NT-proBNP was 22.0 pg/mL (7.0, 61.0). In Cox proportional hazards models allowing for diabetes duration, gender, BMI, smoking status, HbA1c, hypertension status, HDL and non-HDL cholesterol, white blood cell count, estimated glomerular filtration rate and albumin excretion rate, both log hsTnT (HR=1.30, 95% CI: 1.06-1.59) and log NT-proBNP (HR=1.29, 95% CI: 1.13-1.48) independently predicted CVD. However, the prediction of CVD between models with and without these two markers improved only marginally (Uno’s concordance statistic p=0.06). Furthermore, log hsTnT was a slightly weaker predictor of MACE (HR=1.22, 95% CI: 0.97-1.55) compared with log NT-proBNP (HR=1.28, 95% CI: 1.11-1.47). The addition of these two markers to models already including traditional risk factors did not enhance MACE prediction (p=0.39). In conclusion, although hsTnT and NT-proBNP independently predicted both CVD and MACE, they marginally increased the area under the curve only for CAD in this type 1 diabetes cohort. Disclosure T. Costacou: None. A.K. Saenger: None. T.J. Orchard: Consultant; Self; Boehringer Ingelheim International GmbH. Funding National Institutes of Health (DK34818); Rossi Memorial Fund

We investigated residual beta cell function in participants from the DCCT/EDIC study with an average of 35 (range 27, 48) years duration of T1D. Between 2015-2017 after 22-24 years of follow-up in EDIC, a 4-hour mixed meal tolerance test was administered to 944 participants and 7 timed plasma specimens were collected and assayed for C-peptide using a chemiluminescent immunoassay (Roche). We defined a significant post-stimulus response as a peak C-peptide concentration >0.03 nmol/L, based on an earlier DCCT study which demonstrated that the risk of microvascular disease progression was markedly higher among participants who entered the trial with values below this concentration. Overall, 71 (7.5%) participants were classified as “responders” with a median peak C-peptide of 0.10 nmol/L (IQR 0.06, 0.15). Among the 873 participants classified as “non-responders”, 46 had detectable peak C-peptide between 0.003 (limit of detection) and 0.029 nmol/L. Responders were slightly older than non-responders (58.5 ± 6.2 vs. 56.5 ± 6.8 y; p=0.02), yet had similar age of onset of diabetes (22.5 ± 7.0 vs. 21.4 ± 7.8 y) and duration of diabetes (35.9 ± 5.1 vs. 35.0 ± 4.9 y). Compared to non-responders, responders had lower HbA1c values (8.6 ± 1.7 vs. 8.9 ± 1.5%; p=0.01) and higher stimulated C-peptide (0.22 ± 0.14 vs. 0.11 ± 0.11 nmol/L; p In conclusion, beta cell function persists in some very long duration T1D patients and is associated with clinically meaningful reductions in the frequency of severe hypoglycemia. Disclosure R. Gubitosi-Klug: None. B. Braffett: None. S.M. Hitt: None. V. Arends: None. M. Steffes: None. A.K. Saenger: Advisory Panel; Self; Alere Inc. J. Lachin: Board Member; Self; AbbVie Inc., Celgene Corporation. J.P. Palmer: None.