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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

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posted on 16.09.2021, 16:47 by 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, The TODAY Study Group
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.

ResearchDesignandMethods: 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/1.73m2), and rapid eGFR annual decline (>3 ml/min/1.73m2, 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 follow-up of 10.2 ± 4.5 years. Each 1% increment in HbA1c conferred higher risk of microalbuminuria (HR: 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]). Higher SBP 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.

Funding

This work was completed with funding from NIDDK and the NIH Office of the Director through grants U01-DK61212, U01-DK61230, U01-DK61239, U01-DK61242, and U01-DK61254. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The NIDDK project office was involved in all aspects of the study, including: design and conduct; collection, management, analysis, and interpretation of the data; review and approval of the manuscript; and decision to submit the manuscript for publication.

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