TY - JOUR
T1 - Aminoaciduria and metabolic dysregulation during diabetic ketoacidosis
T2 - Results from the diabetic kidney alarm (DKA) study
AU - Melena, Isabella
AU - Piani, Federica
AU - Tommerdahl, Kalie L.
AU - Severn, Cameron
AU - Chung, Linh T.
AU - MacDonald, Alexis
AU - Vinovskis, Carissa
AU - Cherney, David
AU - Pyle, Laura
AU - Roncal-Jimenez, Carlos A.
AU - Lanaspa, Miguel A.
AU - Rewers, Arleta
AU - van Raalte, Daniël H.
AU - Cara-Fuentes, Gabriel
AU - Parikh, Chirag R.
AU - Nelson, Robert G.
AU - Pavkov, Meda E.
AU - Nadeau, Kristen J.
AU - Johnson, Richard J.
AU - Bjornstad, Petter
N1 - Funding Information:
Financial support for this work provided by the Thrasher Research Foundation, ISPAD and JDRF, and NIH CTSA Grant UL1 TR002535. K.L.T. receives salary and research support from NHLBI (K23 HL159292), Children's Hospital Colorado Research Institute Research Scholar Award, University of Colorado Diabetes Research Center (P30 DK116073), Ludeman Family Center for Women's Health Research at the University of Colorado, and the Department of Pediatrics, Section of Endocrinology at the University of Colorado School of Medicine. P.B. receives salary and research support from NIDDK (R01 DK129211, R21 DK129720, K23 DK116720), JDRF (2-SRA-2019-845-S-B), Boettcher Foundation, Ludeman Family Center for Women's Health Research at the University of Colorado, the Department of Pediatrics, Section of Endocrinology and Barbara Davis Center for Diabetes at University of Colorado School of Medicine. PB has acted as a consultant for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Eli-Lilly, Sanofi, Novo Nordisk, and Horizon Pharma. PB serves on the advisory boards for AstraZeneca, Bayer, Boehringer Ingelheim, Novo Nordisk and XORTX. D.Z.I.C has received honoraria from Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, Bayer, Prometric, BMS, Maze and Novo-Nordisk and has received operational funding for clinical trials from Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca and Novo-Nordisk. DvR has acted as a consultant and received honoraria from Boehringer Ingelheim and Lilly, Merck, Novo Nordisk, MSD, Sanofi and AstraZeneca and has received research operating funds from Boehringer Ingelheim-Lilly Diabetes Alliance, AstraZeneca and MDS. All honoraria are paid to his employer (Amsterdam University Medical Center). CP is a member of the advisory board of RenalytixAI and owns equity in the same. He also serves on the DSMB board for Genfit, CP was supported by the grants: R01HL085757, P30DK079310. RJ has acted as a consultant for Horizon and AstraZeneca and has equity with XORTX Therapeutics and Colorado Research Partners LLC. FP, IM, CS, LTC, CV, LP, CRJ, MAL, AR, WO, RGN, MP, KJN have no disclosures.
Funding Information:
Thrasher Research Foundation , ISPAD/JDRF fellowship , and NIH CTSA Grant UL1 TR002535 , NIH K23 DK116720 and NIH R01 DK129211 .
Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/6
Y1 - 2022/6
N2 - 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.
AB - 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.
KW - Aminoaciduria
KW - Diabetic ketoacidosis
KW - Diabetic nephropathy
KW - Pediatrics
KW - Type 1 diabetes
UR - http://www.scopus.com/inward/record.url?scp=85129554744&partnerID=8YFLogxK
U2 - 10.1016/j.jdiacomp.2022.108203
DO - 10.1016/j.jdiacomp.2022.108203
M3 - Article
C2 - 35523653
SN - 1056-8727
VL - 36
JO - Journal of Diabetes and its Complications
JF - Journal of Diabetes and its Complications
IS - 6
M1 - 108203
ER -