TY - JOUR
T1 - Candidate biomarkers as predictors of future kidney disease and cardiovascular dysfunction in adolescents with type 2 diabetes
AU - for theTODAYStudy Group
AU - Bacha, Fida
AU - El ghormli, Laure
AU - Braffett, Barbara H.
AU - Shah, Amy S.
AU - Marcovina, Santica M.
AU - Levitt Katz, Lorraine E.
AU - Willi, Steven M.
AU - Caprio, Sonia
AU - Dhaliwal, Ruban
AU - Gidding, Samuel S.
N1 - Publisher Copyright:
© 2023 Elsevier B.V.
PY - 2023/5
Y1 - 2023/5
N2 - 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.
AB - 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.
KW - Cardiovascular disease
KW - Circulating biomarkers
KW - Kidney disease
KW - Pediatrics
KW - Risk assessment
KW - Type 2 diabetes
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U2 - 10.1016/j.diabres.2023.110671
DO - 10.1016/j.diabres.2023.110671
M3 - Article
C2 - 37068551
AN - SCOPUS:85152921762
SN - 0168-8227
VL - 199
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
M1 - 110671
ER -