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

Authors

Fida Bacha, Texas Children's Hospital and Baylor College of Medicine, 6621 Fannin St, Houston, TX 77030, USA.
Laure El Ghormli, The Biostatistics Center, George Washington University, 6110 Executive Blvd, Rockville, MD 20852, USA.
Barbara H. Braffett, The Biostatistics Center, George Washington University, 6110 Executive Blvd, Rockville, MD 20852, USA. Electronic address: braffett@bsc.gwu.edu.
Amy S. Shah, Cincinnati Children's Hospital and University of Cincinnati, 333 Burnet Ave, Cincinnati, OH 45229, USA.
Santica M. Marcovina, Medpace Reference Laboratories, 5365 Medpace Way, Cincinnati, OH 45227, USA.
Lorraine E. Levitt Katz, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA.
Steven M. Willi, Children's Hospital of Philadelphia, 3401 Civic Center Blvd, Philadelphia, PA 19104, USA.
Sonia Caprio, Department of Pediatric Endocrinology, Yale School of Medicine, 1 Long Warf Dr, New Haven, CT 06519, USA.
Ruban Dhaliwal, State University of New York Upstate Medical University, 766 Irving Ave, Syracuse, NY 13210, USA.
Samuel S. Gidding, Department of Genomic Health, Geisinger, 100 N Academy Ave, Danville, PA 17822, USA.

Document Type

Journal Article

Publication Date

5-1-2023

Journal

Diabetes research and clinical practice

Volume

199

DOI

10.1016/j.diabres.2023.110671

Keywords

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

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 m 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.

APA Citation

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; and Gidding, Samuel S., "Candidate biomarkers as predictors of future kidney disease and cardiovascular dysfunction in adolescents with type 2 diabetes" (2023). GW Authored Works. Paper 2976.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/2976

Department

Epidemiology