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

• Published in: Diabetes research and clinical practice Vol. 199; p. 110671
• Main Authors: Bacha, Fida, El ghormli, Laure, Braffett, Barbara H., Shah, Amy S., Marcovina, Santica M., Levitt Katz, Lorraine E., Willi, Steven M., Caprio, Sonia, Dhaliwal, Ruban, Gidding, Samuel S.
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.05.2023
• Subjects: Adolescent; Albuminuria - urine; Biomarkers - urine; Cardiovascular disease; Circulating biomarkers; Diabetes Mellitus, Type 2 - complications; Female; Glomerular Filtration Rate; Humans; Kidney disease; Kidney Diseases; Male; Pediatrics; Pulse Wave Analysis; Risk assessment; Risk Factors; Type 2 diabetes; Type 2 diabetes; Kidney disease; Pediatrics; Cardiovascular disease; Circulating biomarkers; Risk assessment
• ISSN: 0168-8227; 1872-8227
• DOI: 10.1016/j.diabres.2023.110671

[Display omitted] •Youth with type 2 diabetes have a high burden of kidney and cardiovascular disease.•Biomarkers of endothelial dysfunction, β-cell dysfunction, insulin sensitivity.•Higher E-selectin and proinsulin concentrations associated with kidney disease.•Biomarkers for personalized risk assessments in youth-onset type 2 diabetes. 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. 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. 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. 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.