ADA Presidents' Select Abstract: Structural Lesions on Kidney Biopsy in Youth-Onset Type 1 Diabetes (T1D) and Type 2 Diabetes (T2D)

Recent epidemiological studies suggest a more aggressive clinical course of diabetic kidney disease in youth-onset T2D compared with youth-onset T1D. We compared kidney structural lesions in participants with youth-onset T2D and T1D to determine if youth-onset T2D was associated with greater early tissue injury. Quantitative microscopy was performed on kidney tissue obtained from research kidney biopsies in 27 youth with diabetes (13 T2D, 14 T1D). Group differences in clinical and morphometric parameters were tested using t-tests, Wilcoxon signed-rank test and linear models. At biopsy, the 13 participants with T2D were younger than the 14 with T1D (17±2 vs. 23±2 years; p<0.0001), had shorter diabetes duration (2.4±1.9 vs. 12.3±5.2 years; p<0.0001), but similar HbA1c (6.6±1.0 vs. 7.3±1.0 %; p=0.10) and median urine albumin-to-creatinine ratio (6 [min-max: 1-163] vs. 7 [2-58] mg/g; p=0.96). Youth with T2D exhibited greater glomerular tuft area (17588±4806 vs. 13821±2748 um2, p=0.018), glomerular volume (3.4±1.4 vs. 2.31±0.68 106um3, p=0.018), glomerular nuclear count (101±23 vs. 63±11, p<0.0001) mesangial volume (0.44±0.15 vs. 0.28±0.09 106um3, p=0.002) and mesangial matrix (2291±531 vs. 2001±566 um2, p=0.008). Glomerular sclerosis was only present in one individual with T2D. Despite similar clinical characteristics and considerably shorter diabetes duration, youth with T2D exhibited more severe kidney structural lesions than young persons with youth-onset T1D. Studies are underway to elucidate the metabolic and molecular pathways underlying these structural differences, as well as to delineate potential ultrastructural differences in T2D vs. T1D by electron microscopy. Disclosure V.Nair: None. V.Shah: Advisory Panel; LifeScan Diabetes Institute, Medscape, Consultant; DKSH, Research Support; Novo Nordisk, Tandem Diabetes Care, Inc., Dexcom, Inc., Insulet Corporation, JDRF, National Institutes of Health, Speaker's Bureau; Dexcom, Inc., Insulet Corporation. K.L.Tommerdahl: None. K.Sharma: Advisory Panel; Reata Pharmaceuticals, Inc., Otsuka America Pharmaceutical, Inc. I.De boer: Advisory Panel; AstraZeneca, Boehringer Ingelheim and Eli Lilly Alliance, Boehringer Ingelheim International GmbH, Otsuka America Pharmaceutical, Inc., Bayer Inc., Consultant; George Clinical, Gilead Sciences, Inc., Medscape, Research Support; Dexcom, Inc. P.Saulnier: Board Member; Novo Nordisk, Consultant; Grünenthal Group. H.C.Looker: None. R.G.Nelson: None. J.B.Hodgin: None. P.Bjornstad: Advisory Panel; AstraZeneca, Novo Nordisk, Lilly, Horizon Therapeutics plc, Boehringer Ingelheim (Canada) Ltd., LG Chem, Consultant; Bayer Inc., Bristol-Myers Squibb Company. A.Naik: Advisory Panel; CareDx. F.Alakwaa: None. J.A.Schaub: None. T.B.Vigers: None. M.Bitzer: None. L.Pyle: None. F.C.Brosius: Advisory Panel; Gilead Sciences, Inc. P.E.Ladd: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases; JDRF