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

Authors: BACHA, FIDA - Children'S Nutrition Research Center (CNRC); EL GHORMLI, LAURE - George Washington University; BRAFFETT, BARBARA - George Washington University; SHAH, AMY - Cincinnati Children'S Research Hospital; MARCOVINA, SANTICA - Medpace Reference Laboratories; LEVITT KATZ, LORRAINE - Children'S Hospital - Philadelphia, Pennsylvania; WILLI, STEVEN - Children'S Hospital - Philadelphia, Pennsylvania; CAPRIO, SONIA - Yale School Of Medicine; DHALIWAL, RUBAN - State University Of New York (SUNY); GIDDING, SAMUEL - Geisinger Medical Center

Submitted to: Diabetes Research and Clinical Practice
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/11/2023
Publication Date: 4/15/2023
Citation: Bacha, F., El Ghormli, L., Braffett, B.H., Shah, A.S., Marcovina, S.M., Levitt Katz, L.E., Willi, S.M., Caprio, S., Dhaliwal, R., Gidding, S.S., for the Today Study Group. 2023. Candidate biomarkers as predictors of future kidney disease and cardiovascular dysfunction in adolescents with type 2 diabetes. Diabetes Research and Clinical Practice. 199. Article 110671. https://doi.org/10.1016/j.diabres.2023.110671.
DOI: https://doi.org/10.1016/j.diabres.2023.110671

Interpretive Summary: Little is known about the impact of early attainment of tight glucose control on long-term glycemic control in youth-onset type 2 diabetes, and whether early goo control of glucose can prevent the rapid decline in insulin secretion in these children. This study in youth with type 2 diabetes involved with the TODAY study examined whether early good glucose control was protective of the pancreas insulin secretion ability over long-term follow-up of these teens into young adulthood. Researchers from Houston and others demonstrated that early glycemic control in the TODAY study translated to better long-term glycemic control. However, tight early glycemic control did not prevent deterioration of the pancreatic B-cell function. Additional studies with more prolonged follow-up are needed.

Technical Abstract: 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 B-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.