Isabella Melena1, Federica Piani2, Kalie L Tommerdahl3, Cameron Severn4, Linh T Chung5, Alexis MacDonald1, Carissa Vinovskis1, David Cherney6, Laura Pyle4, Carlos A Roncal-Jimenez5, Miguel A Lanaspa5, Arleta Rewers7, Daniël H van Raalte8, Gabriel Cara-Fuentes9, Chirag R Parikh10, Robert G Nelson11, Meda E Pavkov12, Kristen J Nadeau1, Richard J Johnson5, Petter Bjornstad13. 1. Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA. 2. Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy. 3. Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Barbara Davis Center for Diabetes, University of Colorado School of Medicine, Aurora, CO, USA. 4. Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Biostatistics and Informatics, Colorado School of Public Health, CO, USA. 5. Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA. 6. Department of Medicine, Division of Nephrology, University of Toronto School of Medicine, Toronto, Ontario, Canada. 7. Department of Pediatrics, Section of Emergency Medicine, University of Colorado School of Medicine, Aurora, CO, USA. 8. Diabetes Center, Department of Internal Medicine, Amsterdam University Medical Centers, location VUmc, Amsterdam, the Netherlands. 9. Department of Pediatrics, Section of Nephrology, University of Colorado School of Medicine, Aurora, CO, USA. 10. Department of Medicine, Division of Nephrology, Johns Hopkins University, Baltimore, MD, USA. 11. Chronic Kidney Disease Section, Phoenix Epidemiology and Clinical Research Branch, NIDDK, Phoenix, AZ, USA. 12. Division of Diabetes Translation, Centers for Disease Control and Prevention, Atlanta, GA, USA. 13. Department of Pediatrics, Section of Endocrinology, University of Colorado School of Medicine, Aurora, CO, USA; Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado School of Medicine, Aurora, CO, USA. Electronic address: petter.m.bjornstad@cuanschutz.edu.
Abstract
OBJECTIVE: We examined changes in the excretion of various amino acids and in glycolysis and ketogenesis-related metabolites, during and after diabetic ketoacidosis (DKA) diagnosis, in youth with known or new onset type 1 diabetes (T1D). METHODS: Urine samples were collected from 40 youth with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, blood glucose 451 ± 163 mg/dL) at 3 time points: 0-8 h and 12-24 h after starting an insulin infusion, and 3 months after hospital discharge. Mixed-effects models evaluated the changes in amino acids and other metabolites in the urine. RESULTS: Concentrations of urine histidine, threonine, tryptophan, and leucine per creatinine were highest at 0-8 h (148.8 ± 23.5, 59.5 ± 12.3, 15.4 ± 1.4, and 24.5 ± 2.4% of urine creatinine, respectively), and significantly decreased over 3 months (p = 0.028, p = 0.027, p = 0.019, and p < 0.0001, respectively). Urine histidine, threonine, tryptophan, and leucine per urine creatinine decreased by 10.6 ± 19.2, 0.7 ± 0.9, 1.3 ± 0.9, and 0.5 ± 0.3-fold, respectively, between 0 and 8 h and 3 months. CONCLUSIONS: In our study, DKA was associated with profound aminoaciduria, suggestive of proximal tubular dysfunction analogous to Fanconi syndrome.
OBJECTIVE: We examined changes in the excretion of various amino acids and in glycolysis and ketogenesis-related metabolites, during and after diabetic ketoacidosis (DKA) diagnosis, in youth with known or new onset type 1 diabetes (T1D). METHODS: Urine samples were collected from 40 youth with DKA (52% boys, mean age 11 ± 4 years, venous pH 7.2 ± 0.1, blood glucose 451 ± 163 mg/dL) at 3 time points: 0-8 h and 12-24 h after starting an insulin infusion, and 3 months after hospital discharge. Mixed-effects models evaluated the changes in amino acids and other metabolites in the urine. RESULTS: Concentrations of urine histidine, threonine, tryptophan, and leucine per creatinine were highest at 0-8 h (148.8 ± 23.5, 59.5 ± 12.3, 15.4 ± 1.4, and 24.5 ± 2.4% of urine creatinine, respectively), and significantly decreased over 3 months (p = 0.028, p = 0.027, p = 0.019, and p < 0.0001, respectively). Urine histidine, threonine, tryptophan, and leucine per urine creatinine decreased by 10.6 ± 19.2, 0.7 ± 0.9, 1.3 ± 0.9, and 0.5 ± 0.3-fold, respectively, between 0 and 8 h and 3 months. CONCLUSIONS: In our study, DKA was associated with profound aminoaciduria, suggestive of proximal tubular dysfunction analogous to Fanconi syndrome.
Authors: Joseph I Wolfsdorf; Jeremy Allgrove; Maria E Craig; Julie Edge; Nicole Glaser; Vandana Jain; Warren W R Lee; Lucy N W Mungai; Arlan L Rosenbloom; Mark A Sperling; Ragnar Hanas Journal: Pediatr Diabetes Date: 2014-07-12 Impact factor: 4.866
Authors: Christopher B Newgard; Jie An; James R Bain; Michael J Muehlbauer; Robert D Stevens; Lillian F Lien; Andrea M Haqq; Svati H Shah; Michelle Arlotto; Cris A Slentz; James Rochon; Dianne Gallup; Olga Ilkayeva; Brett R Wenner; William S Yancy; Howard Eisenson; Gerald Musante; Richard S Surwit; David S Millington; Mark D Butler; Laura P Svetkey Journal: Cell Metab Date: 2009-04 Impact factor: 27.287
Authors: Kristen J Nadeau; Phillip S Zeitler; Timothy A Bauer; Mark S Brown; Jennifer L Dorosz; Boris Draznin; Jane E B Reusch; Judith G Regensteiner Journal: J Clin Endocrinol Metab Date: 2009-07-07 Impact factor: 5.958
Authors: Denise E Lackey; Christopher J Lynch; Kristine C Olson; Rouzbeh Mostaedi; Mohamed Ali; William H Smith; Fredrik Karpe; Sandy Humphreys; Daniel H Bedinger; Tamara N Dunn; Anthony P Thomas; Pieter J Oort; Dorothy A Kieffer; Rajesh Amin; Ahmed Bettaieb; Fawaz G Haj; Paska Permana; Tracy G Anthony; Sean H Adams Journal: Am J Physiol Endocrinol Metab Date: 2013-03-19 Impact factor: 4.310