American Diabetes Association
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Structural Lesions on Kidney Biopsy in Youth-Onset and Adult-Onset Type 2 Diabetes

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posted on 2022-01-10, 14:47 authored by Helen C. Looker, Laura Pyle, Tim Vigers, Cameron Severn, Pierre Saulnier, Behzad Najafian, Mike Mauer, Robert G. Nelson, Petter Bjornstad
Objective: Type 2 diabetes (T2D) is a leading cause of end stage kidney disease (ESKD) worldwide. Recent studies suggest a more aggressive clinical course of diabetic kidney disease (DKD) in youth-onset than adult-onset T2D. We compared kidney structural lesions in youth- and adult-onset T2D to determine if youth-onset was associated with greater early tissue injury.

Methods: Quantitative microscopy was performed on kidney tissue obtained from research kidney biopsies in 161 Pima Indians (117 women, 44 men) with T2D. Onset of T2D was established by serial oral glucose tolerance testing and participants were stratified as youth-onset (<25 years) or adult-onset (≥25 years). Associations between clinical and morphometric parameters and age of onset were tested using linear models.

Results: At biopsy, the 52 participants with youth-onset T2D were younger than the 109 with adult-onset T2D (39.1±9.9 vs. 51.4±10.2 years, p<0.0001), but their diabetes duration was similar (19.3±8.1 vs. 17.0±7.8 years, p=0.09). Median urine albumin-to-creatinine ratio was higher in the youth-onset group (58 [25th-75th percentile, 17-470] vs. 27 [13-73] mg/g, p=0.02). Youth-onset participants had greater glomerular basement membrane (GBM) width (552±128 nm vs. 490±114nm, p=0.002) and mesangial fractional volume (0.31±0.10 vs. 0.27±0.08, p=0.001) than adult-onset participants. Percentage glomerular sclerosis, glomerular volume, mesangial fractional volume, and GBM width were also inversely associated with age of diabetes onset as a continuous variable.

Conclusion: Younger age of T2D onset strongly associates with more severe kidney structural lesions. Studies are underway to elucidate the pathways underlying these associations.


Financial support for this work provided by the American Diabetes Association (Clinical Science Award 1-08-CR-42) and by the Intramural Research Program of the NIDDK. P.B. receives salary and research support from NIDDK (R01 DK129211, R21 DK129720, K23 DK116720, UC DK114886 and P30 DK116073), JDRF (2-SRA-2019-845-S-B, 3-SRA-2017-424-M-B), Boettcher Foundation, American Heart Association (20IPA35260142), Center for Women’s Health Research at University of Colorado, the Department of Pediatrics, Section of Endocrinology and Barbara Davis Center for Diabetes at University of Colorado School of Medicine.


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