Attenuated kidney oxidative metabolism in young adults with type 1 diabetes.

Autor:	Choi YJ; Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, United States of America., Richard G; Department of Medicine, Division of Neurology, Université de Sherbrooke, Québec, Canada., Zhang G; Center for Renal Precision Medicine, University of Texas Health-San Antonio, San Antonio, United States of America., Hodgin JB; Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, United States of America., Demeke DS; Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, United States of America., Yang Y; Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, United States of America., Schaub JA; Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, United States of America., Tamayo IM; Center for Renal Precision Medicine, University of Texas Health-San Antonio, San Antonio, United States of America., Gurung BK; Center for Renal Precision Medicine, University of Texas Health-San Antonio, San Antonio, United States of America., Naik AS; Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, United States of America., Nair V; Department of Internal Medicine, Division of Nephrology, University of Michigan Medical School, Ann Arbor, United States of America., Birznieks C; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., MacDonald A; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., Narongkiatikhun P; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., Gross S; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., Driscoll L; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., Flynn M; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., Tommerdahl K; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., Nadeau KJ; Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, United States of America., Shah VN; Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, United States of America., Vigers T; Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, United States of America., Snell-Bergeon JK; Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, United States of America., Kendrick J; Barbara Davis Center for Childhood Diabetes, University of Colorado School of Medicine, Aurora, United States of America., van Raalte DH; Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, Amsterdam, Netherlands., Li LP; Radiology Department, Endeavor Health, Pritzker School of Medicine, University of Chicago, Chicago, United States of America., Prasad P; Radiology Department, Endeavor Health, Pritzker School of Medicine, University of Chicago, Chicago, United States of America., Ladd P; Department of Radiology, University of Colorado School of Medicine, Aurora, United States of America., Chin BB; Department of Radiology, University of Colorado School of Medicine, Aurora, United States of America., Cherney DZ; Department of Medicine, Division of Nephrology, University of Toronto School of Medicine, Toronto, Canada., McCown PJ; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, United States of America., Alakwaa F; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, United States of America., Otto EA; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, United States of America., Brosius FC; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, United States of America., Saulnier PJ; Clinical Investigation Center, University of Poitiers, Poitiers, France., Puelles VG; III. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany., Goodrich JA; Department of Population and Public Health Sciences, University of Southern California, Los Angeles, United States of America., Street K; Department of Biostatistics, University of Southern California, Los Angeles, United States of America., Venkatachalam MA; Department of Pathology, University of Texas Health Science Center, San Antonio, United States of America., Ruiz A; SygnaMap, Inc., San Antonio, United States of America., de Boer IH; Kidney Research Institute, University of Washington, Seattle, United States of America., Nelson RG; Chronic Kidney Disease Section, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Phoenix, United States of America., Pyle L; Department of Biostatistics and Informatics, University of Colorado School of Medicine, Aurora, United States of America., Blondin DP; Department of Medicine, Division of Neurology, Université de Sherbrooke, Québec, Canada., Sharma K; Center for Renal Precision Medicine, University of Texas Health-San Antonio, San Antonio, United States of America., Kretzler M; Department of Internal Medicine, Division of Nephrology, University of Michigan, Ann Arbor, United States of America., Bjornstad P; Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, University of Washington School of Medicine, Seattle, United States of America.
Jazyk:	angličtina
Zdroj:	The Journal of clinical investigation [J Clin Invest] 2024 Oct 22. Date of Electronic Publication: 2024 Oct 22.
DOI:	10.1172/JCI183984
Abstrakt:	Background: In type 1 diabetes (T1D), impaired insulin sensitivity may contribute to the development of diabetic kidney disease (DKD) through alterations in kidney oxidative metabolism. Methods: Young adults with T1D (n = 30) and healthy controls (HC, n = 20) underwent hyperinsulinemic-euglycemic clamp studies, MRI, 11C-acetate PET, kidney biopsies, single-cell RNA sequencing, and spatial metabolomics to assess this relationship. Results: Participants with T1D had significantly higher glomerular basement membrane thickness compared to HC. T1D participants exhibited lower insulin sensitivity and cortical oxidative metabolism, correlating with higher insulin sensitivity. Proximal tubular transcripts of TCA cycle and oxidative phosphorylation enzymes were lower in T1D. Spatial metabolomics showed reductions in tubular TCA cycle intermediates, indicating mitochondrial dysfunction. The Slingshot algorithm identified a lineage of proximal tubular cells progressing from stable to adaptive/maladaptive subtypes, using pseudotime trajectory analysis, which computationally orders cells along a continuum of states. This analysis revealed distinct distribution patterns between T1D and HC, with attenuated oxidative metabolism in T1D attributed to a greater proportion of adaptive/maladaptive subtypes with low expression of TCA cycle and oxidative phosphorylation transcripts. Pseudotime progression associated with higher HbA1c, BMI, GBM, and lower insulin sensitivity and cortical oxidative metabolism. Conclusion: These early structural and metabolic changes in T1D kidneys may precede clinical DKD. Clinicaltrials: gov NCT04074668.
Databáze:	MEDLINE
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