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