TY - JOUR
T1 - Relative hypoxia and early diabetic kidney disease in type 1 diabetes
AU - Vinovskis, Carissa
AU - Li, Lu-Ping
AU - Prasad, Pottumarthi
AU - Tommerdahl, Kalie
AU - Pyle, Laura
AU - Nelson, Robert G.
AU - Pavkov, Meda E.
AU - van Raalte, Daniel
AU - Rewers, Marian
AU - Pragnell, Marlon
AU - Mahmud, Farid H.
AU - Cherney, David Z.
AU - Johnson, Richard J.
AU - Nadeau, Kristen J.
AU - Bjornstad, Petter
N1 - Funding Information: Funding. Financial support for this work was provided by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Diabetic Complications Consortium (RRID:SCR_001415, www.diacomp.org), grants DK-076169 and DK115255 (18AU3871 [P.B.]), JDRF International grant 2-SRA-2018-627-M-B (P.B.), and National Institutes of Health NIDDK grant K23-DK-116720 (P.B.), National Heart, Lung, and Blood Institute grant K24-HL145076 (K.J.N.), and UL1-RR025780 (University of Colorado Denver), support from the Center for Women’s Health Research at University of Colorado, the Department of Pediatrics, Section of Endocrinology and Barbara Davis Center for Diabetes at University of Colorado School of Medicine, and by the Intramural Research Program of the NIDDK. Duality of Interest. P.B. has consulted for AstraZeneca, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Sanofi, Novo Nordisk, and Horizon Pharma and serves on the advisory boards of XORTX Therapeutics and Boehringer Ingelheim. No other potential conflicts of interest relevant to this article were reported. Author Contributions. C.V. and P.B. wrote the manuscript and researched data. L.-P.L assisted with MRI postprocessing and analyses. P.P and L.P. developed the MRI protocols, postprocessing, and analyses. K.T. contributed to discussion and reviewed and edited the manuscript. L.P. was responsible for data analyses, contributed to the discussion, and reviewed and edited the manuscript. R.G.N. and his laboratory measured the iohexol and PAH concentrations, contributed to the discussion, and reviewed and edited the manuscript. M.E.P., D.v.R., M.P., and F.H.M. contributed to discussion and reviewed and edited the manuscript. M.R., D.Z.C., R.J.J., and K.J.N. assisted in study design, contributed to the discussion, and reviewed and edited the manuscript. P.B. designed the study. L.P. and P.B. are the guarantors of this work and, as such, had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Prior Presentation. Parts of this study were presented as an oral presentation at the 80th Scientific Sessions of the American Diabetes Association, 12–16 June 2020. Publisher Copyright: © 2020 by the American Diabetes Association. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/12/1
Y1 - 2020/12/1
N2 - The objective of this study was to compare the ratio of renal oxygen availability (RO2)toglomerularfiltration rate (GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO2 was estimated by blood oxygen level–dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and p-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and M/I was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%). The RO2:GFR (ms/ mL/min) was calculated as RO2 (T2*, ms) divided by GFR (mL/min). Whole-kidney RO2:GFR was 25% lower in adolescents with T1D versus control patients (P < 0.0001). In adolescents with T1D, lower whole-kidney RO2:GFR was associated with higher UACR (r =-0.31, P = 0.03), RPF (r =-0.52, P = 0.0009), and fat mass (r =-0.33, P = 0.02). Lower medullary RO2:GFR was associated with lower M/I (r = 0.31, P = 0.03). In conclu-sion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.
AB - The objective of this study was to compare the ratio of renal oxygen availability (RO2)toglomerularfiltration rate (GFR), a measure of relative renal hypoxia, in adolescents with and without type 1 diabetes (T1D) and relate the ratio to albuminuria, renal plasma flow (RPF), fat mass, and insulin sensitivity (M/I). RO2 was estimated by blood oxygen level–dependent MRI; fat mass was estimated by DXA; GFR and RPF were estimated by iohexol and p-aminohippurate clearance; albuminuria was estimated by urine albumin-to-creatinine ratio (UACR); and M/I was estimated from steady-state glucose infusion rate/insulin (mg/kg/min) by hyperglycemic clamp in 50 adolescents with T1D (age 16.1 ± 3.0 years, HbA1c 8.6 ± 1.2%) and 20 control patients of similar BMI (age 16.1 ± 2.9 years, HbA1c 5.2 ± 0.2%). The RO2:GFR (ms/ mL/min) was calculated as RO2 (T2*, ms) divided by GFR (mL/min). Whole-kidney RO2:GFR was 25% lower in adolescents with T1D versus control patients (P < 0.0001). In adolescents with T1D, lower whole-kidney RO2:GFR was associated with higher UACR (r =-0.31, P = 0.03), RPF (r =-0.52, P = 0.0009), and fat mass (r =-0.33, P = 0.02). Lower medullary RO2:GFR was associated with lower M/I (r = 0.31, P = 0.03). In conclu-sion, adolescents with T1D exhibited relative renal hypoxia that was associated with albuminuria and with increased RPF, fat mass, and insulin resistance. These data suggest a potential role of renal hypoxia in the development of diabetic kidney disease.
UR - http://www.scopus.com/inward/record.url?scp=85096570105&partnerID=8YFLogxK
U2 - https://doi.org/10.2337/db20-0457
DO - https://doi.org/10.2337/db20-0457
M3 - Article
C2 - 32737116
SN - 0012-1797
VL - 69
SP - 2700
EP - 2708
JO - Diabetes
JF - Diabetes
IS - 12
ER -