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

Helen C. Looker, Laura Pyle, Tim Vigers, Cameron Severn, Pierre J. Saulnier, Behzad Najafian, Michael Mauer, Robert G. Nelson, Petter Bjornstad

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

OBJECTIVE: Type 2 diabetes (T2D) is a leading cause of end-stage kidney disease worldwide. Recent studies suggest a more aggressive clinical course of diabetic kidney disease in youth-onset compared with 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.

RESEARCH DESIGN AND 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 (age <25 years) or adult onset (age ≥25 years). Associations between clinical and morphometric parameters and age at 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 vs. 490 ± 114 nm; P = 0.002) and mesangial fractional volume (0.31 ± 0.10 vs. 0.27 ± 0.08; P = 0.001) than adult-onset participants. Glomerular sclerosis percentage, glomerular volume, mesangial fractional volume, and GBM width were also inversely associated with age at diabetes onset as a continuous variable.

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

Original languageEnglish (US)
Pages (from-to)436-443
Number of pages8
JournalDiabetes care
Volume45
Issue number2
DOIs
StatePublished - Feb 2022

Bibliographical note

Funding Information:
Acknowledgments. The authors acknowl edge the work of Lois I. Jones, Enrique Diaz, Bernadine Waseta, Camille Waseta, Julie Paul, and Joey de Keizer. Funding. Financial support for this work was provided by the American Diabetes Association (Clinical Science Award 1-08-CR-42) and by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases (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 and 3-SRA-2017-424-M-B), Boettcher Foundation, American Heart Association (20IPA35260142), Center for Women’s Health Research at University of Colorado, and Department of Pediatrics, Section of Endocrinology, and Barbara Davis Center for Diabetes at University of Colorado School of Medicine. Duality of Interest. P.B. has acted as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli Lilly, Sanofi, Novo Nordisk, and Horizon Pharma and serves on the advisory boards for AstraZe-neca, Bayer, Boehringer Ingelheim, Novo Nordisk, and XORTX Therapeutics. P.J.S. has acted as a consultant for AstraZeneca. M.M. reports having consultancy agreements with Amicus Therapeutics, Avrobio, Bayer, Boeheringer Ingelheim, Freeline Therapeutics, Sangamo Therapeutics, and Sanofi/Genzyme; receiving honoraria from Amicus Therapeutics, Freeline Therapeutics, and Sanofi/Genzyme; receiving research funding from Amicus Therapeutics and Sanofi/Genzyme; and serving on the North American Fabry Registry Board. B.N. reports having consultancy agreements with Amicus Therapeutics, Avrobio, 4D Molecular Therapeutics, Freeline Therapeutics, Sangamo Therapeutics, and Sanofi; serving as a scientific advisor for or member of Amicus Therapeutics, Freeline Therapeutics, and Sanofi; and receiving research funding and honoraria from Amicus Therapeutics and Sanofi. No

Publisher Copyright:
© 2022, American Diabetes Association Inc. All rights reserved.

Keywords

  • Adolescent
  • Adult
  • Biopsy/adverse effects
  • Child, Preschool
  • Diabetes Mellitus, Type 2/complications
  • Diabetic Nephropathies/etiology
  • Female
  • Glomerular Filtration Rate
  • Humans
  • Kidney
  • Kidney Function Tests
  • Male

PubMed: MeSH publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural
  • Journal Article
  • Research Support, N.I.H., Extramural

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