Relative Hypoxia and Early Diabetic Kidney Disease in Type 1 Diabetes

Diabetes. 2020 Dec;69(12):2700-2708. doi: 10.2337/db20-0457. Epub 2020 Jul 31.

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.

Trial registration: ClinicalTrials.gov NCT03618420 NCT03584217.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

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

Associated data

  • figshare/10.2337/figshare.12728423
  • ClinicalTrials.gov/NCT03618420
  • ClinicalTrials.gov/NCT03584217