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.

中文翻译：

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青年发病和成人发病 2 型糖尿病肾活检的结构性病变

目标 2 型糖尿病 (T2D) 是全球终末期肾病的主要原因。最近的研究表明，与成年发病的 T2D 相比，青年发病的糖尿病肾病临床病程更具侵袭性。我们比较了青年和成人 T2D 的肾脏结构病变，以确定青年发病是否与更大的早期组织损伤有关。研究设 通过连续口服葡萄糖耐量测试确定 T2D 的发病，并将参与者分为青年发病（年龄 < 25 岁）或成人发病（年龄 ≥ 25 岁）。使用线性模型测试临床和形态测量参数与发病年龄之间的关联。结果 在活检时，52 名青年发病的 T2D 参与者比 109 名成人发病的 T2D 参与者年轻（39.1 ± 9.9 对 51.4 ± 10.2 岁；P < 0.0001），但他们的糖尿病病程相似（19.3 ± 8.1 对 17.0 ± 7.8年；P = 0.09）。青年发病组的中位尿白蛋白与肌酐比率较高（58 [25-75% 17-470] vs. 27 [13-73] mg/g；P = 0.02）。与成人相比，青年发病参与者的肾小球基底膜 (GBM) 宽度（552 ± 128 对 490 ± 114 nm；P = 0.002）和系膜体积分数（0.31 ± 0.10 对 0.27 ± 0.08；P = 0.001）更大参与者。作为连续变量，肾小球硬化百分比、肾小球体积、系膜体积分数和 GBM 宽度也与糖尿病发病年龄呈负相关。结论 T2D 发病年龄较小与更严重的肾脏结构损伤密切相关。正在进行研究以阐明这些关联背后的途径。