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

J Pediatr. 2018 Jan;192:86-92.e5. doi: 10.1016/j.jpeds.2017.09.012.


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/m2.7), 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Biomarkers / blood*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnostic imaging
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / physiopathology
  • Child
  • Combined Modality Therapy
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diabetes Mellitus, Type 2 / therapy*
  • Diet Therapy
  • Drug Therapy, Combination
  • Echocardiography
  • Exercise Therapy
  • Female
  • Follow-Up Studies
  • Heart Ventricles / diagnostic imaging
  • Heart Ventricles / physiopathology
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Male
  • Metformin / therapeutic use
  • Risk Factors
  • Rosiglitazone
  • Thiazolidinediones / therapeutic use
  • Treatment Outcome
  • Ventricular Function, Left


  • Biomarkers
  • Hypoglycemic Agents
  • Thiazolidinediones
  • Rosiglitazone
  • Metformin

Associated data