Cardiac Biomarkers in Youth with Type 2 Diabetes Mellitus: Results from the TODAY Study

Abstract

Objectives: To examine cardiac biomarkers over time in youth-onset type 2 diabetes, and relate serum concentrations to cardiovascular disease risk factors, and left ventricular structure and function.

Study design: TODAY (Treatment Options for type 2 Diabetes in Adolescents and Youth) was a multicenter randomized trial of 3 treatments including 521 participants with type 2 diabetes, aged 10-17 years, and with 2-6 years of follow-up. Participants were 36% male, obese, and ethnically diverse. Annual serum concentrations of brain natriuretic peptide, troponin, tumor necrosis factor (TNF)-α, receptors 1 and 2 were related to blood pressure, body mass index, hemoglobin A1c, and left ventricular ejection fraction, diastolic function, relative wall thickness, and mass.

Results: Elevated concentrations of brain natriuretic peptide (≥100 pg/mL), TNF-α (≥5.6 pg/mL) and troponin (≥0.01 ng/mL), were present in 17.8%, 18.3%, and 34.2% of the cohort, respectively, at baseline, and in 15.4%, 17.1%, and 31.1% at the end of the study, with wide variability over time, without persistence in individuals or clear relationship to glycemia or cardiovascular structure/function. TNF receptors concentrations were increased at baseline and not significantly different from end-of-study concentrations. Adverse echocardiographic measures were more likely in the highest TNF receptor tertile (all P < .05): higher left ventricular mass (39.3 ± 9.0 g/m^2.7), left atrial internal dimension (3.7 ± 0.4 cm) and E/Em ratio, a measure of diastolic dysfunction (6.2 ± 1.9). After adjustment for body mass index, these relationships were no longer significant.

Conclusions: Elevated serum concentrations of cardiac biomarkers were common in youth with type 2 diabetes, but their clinical significance is unclear and will require further long-term study.

Trial registration: ClinicalTrials.govNCT00081328.

Keywords: adolescent; cardiac biomarkers; cardiovascular function; cardiovascular risk factors; type 2 diabetes.

Figure

Baseline and end-of-study distributions of measures of A, BNP, B, troponin, C, TNF-α, D, TNF-R1, and E, TNF-R2. A reference line (dashed line) and the percent of participants above a pre-specified abnormal cutoff is illustrated in the graph for BNP (cutoff, 100 pg/mL), troponin (cutoff, 0.01 ng/mL), and TNF-α (5.6 pg/mL). TNF-R1 and TNF-R2 are normally distributed and therefore the mean (SD) is given; the reference line (dashed line) represents the upper normal range reported in the literature (TNF-R1: 821 pg/mL, and TNF-R2: 2622 pg/mL).