Candidate biomarkers as predictors of future kidney disease and cardiovascular dysfunction in adolescents with type 2 diabetes

Diabetes Res Clin Pract. 2023 May:199:110671. doi: 10.1016/j.diabres.2023.110671. Epub 2023 Apr 15.

Abstract

Aims: Evaluate changes in circulating biomarkers as predictors of kidney disease, and cardiac/vascular dysfunction in participants from the Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) study.

Methods: Candidate biomarkers were assessed annually in 507 participants over a mean follow-up of 6.9 ± 2.4 years. Moderate albuminuria was defined as urine albumin-to-creatinine ratio ≥ 30 mg/g and hyperfiltration as eGFR ≥ 135 mL/min/1.73 m2 at two consecutive visits. Echocardiography (n = 256) and pulse wave velocity (n = 193) were evaluated twice, 5 years apart. Adjusted Cox proportional hazard models and logistic regression models were used to examine associations between biomarkers and outcomes.

Results: At baseline, 35.7% were male, with a mean age 13.9 years, diabetes duration 7.8 months, and HbA1c 6.0%. Higher concentrations of E-selectin and proinsulin were associated with incident moderate albuminuria and hyperfiltration. Higher concentrations of FGF-23 were associated with lower risk of hyperfiltration and negatively correlated with eGFR. No candidate biomarkers predicted a decline in cardiac or vascular function.

Conclusions: Circulating biomarkers of endothelial dysfunction and markers of β-cell dysfunction and insulin sensitivity could be used in a more personalized risk assessment of kidney disease in youth-onset type 2 diabetes. However, biomarkers studied have limited value in predicting cardiac dysfunction or vascular stiffness.

Keywords: Cardiovascular disease; Circulating biomarkers; Kidney disease; Pediatrics; Risk assessment; Type 2 diabetes.

MeSH terms

  • Adolescent
  • Albuminuria / urine
  • Biomarkers / urine
  • Diabetes Mellitus, Type 2* / complications
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney Diseases*
  • Male
  • Pulse Wave Analysis
  • Risk Factors

Substances

  • Biomarkers