Effects of Metabolic Factors, Race-Ethnicity, and Sex on the Development of Nephropathy in Adolescents and Young Adults With Type 2 Diabetes: Results From the TODAY Study
TODAY Study Group, Petter Bjornstad, Laure El ghormli, Kara S. Hughan, Lori M. Laffel, Kristen J. Nadeau, Maria Rayas, Bereket Tesfaldet, Sherida E. Tollefsen, Steven M. Willi, Jane Lynch
Abstract
OBJECTIVE To describe the longitudinal effects of sex, race-ethnicity, and metabolic factors on the risk of developing diabetic kidney disease (DKD) in the Treatment Options for Type 2 Diabetes in Adolescents and Youth (TODAY) cohort. RESEARCH DESIGN AND METHODS Urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) by serum creatinine and cystatin C were assessed annually for up to 15 years after study entry. Markers of DKD included micro- and macroalbuminuria (UACR ≥30 mg/g and ≥300 mg/g, respectively), hyperfiltration (eGFR ≥135 mL/min/1.73 m2), and rapid eGFR annual decline (>3 mL/min/1.73 m2 and/or ≥3.3%). The relationships between risk factors and DKD were evaluated longitudinally using time-to-event models. RESULTS Data were available on 677 participants, average age at baseline 14 years, with a mean ± SD follow-up of 10.2 ± 4.5 years. Each 1% increment in HbA1c conferred higher risk of microalbuminuria (hazard ratio 1.24 [95% CI 1.18, 1.30]), macroalbuminuria (1.22, [1.11, 1.34]), hyperfiltration (1.11, [1.05, 1.17]), and rapid eGFR decline (1.12, [1.04, 1.20]). No sex or race-ethnicity differences were observed for the 14-year cumulative incidence of elevated albuminuria. Higher systolic blood pressure and baseline serum uric acid, and lower indices of β-cell function (C-peptide index and oral disposition index [oDI]), increased the risk of microalbuminuria, while higher triglycerides increased risk of micro- and macroalbuminuria. Lower oDI levels, female sex, and Hispanic ethnicity were associated with higher risk of hyperfiltration. CONCLUSIONS Elevated HbA1c was a shared risk factor among all phenotypes of DKD in this longitudinal cohort of adolescents and young adults with youth-onset type 2 diabetes. Other risk factors included elevated blood pressure, triglycerides, serum uric acid, and β-cell dysfunction.