Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes.

Abstract

The objective of this study was to compare the ratio of renal oxygen availability (RO2) to glomerular filtration 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 conclusion, 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.

• Authors: Carissa Vinovskis, Lu-Ping Li, Pottumarthi Prasad, Kalie Tommerdahl, Laura Pyle, Robert G Nelson, Meda E Pavkov, Daniel van Raalte, Marian Rewers, Marlon Pragnell, Farid H Mahmud, David Z Cherney, Richard J Johnson, Kristen J Nadeau, Petter Bjornstad
• Journal: Diabetes (Diabetes) Vol. 69 Issue 12 Pg. 2700-2708 (12 2020) ISSN: 1939-327X [Electronic] United States
• PMID: 32737116 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 by the American Diabetes Association.

Chemical References

• Glycated Hemoglobin A
• Insulin
• hemoglobin A1c protein, human
• Iohexol
• Furosemide
• Oxygen
• p-Aminohippuric Acid

Topics

• Adiposity
• Adolescent
• Body Composition
• Child
• Diabetes Mellitus, Type 1 (complications, metabolism)
• Diabetic Nephropathies
• Female
• Furosemide
• Glomerular Filtration Rate
• Glucose Clamp Technique
• Glycated Hemoglobin (genetics, metabolism)
• Humans
• Hypoxia
• Insulin
• Iohexol (pharmacology)
• Male
• Oxygen (metabolism)
• Young Adult
• p-Aminohippuric Acid (pharmacology)