Sexual dimorphism in the progression of type 2 diabetic kidney disease in T2DN rats

Physiol Genomics. 2021 Jun 1;53(6):223-234. doi: 10.1152/physiolgenomics.00009.2021. Epub 2021 Apr 19.


Diabetic kidney disease (DKD) is a common complication of diabetes, which frequently leads to end-stage renal failure and increases cardiovascular disease risk. Hyperglycemia promotes renal pathologies such as glomerulosclerosis, tubular hypertrophy, microalbuminuria, and a decline in glomerular filtration rate. Importantly, recent clinical data have demonstrated distinct sexual dimorphism in the pathogenesis of DKD in people with diabetes, which impacts both severity- and age-related risk factors. This study aimed to define sexual dimorphism and renal function in a nonobese type 2 diabetes model with the spontaneous development of advanced diabetic nephropathy (T2DN rats). T2DN rats at 12- and over 48-wk old were used to define disease progression and kidney injury development. We found impaired glucose tolerance and glomerular hyperfiltration in T2DN rats to compare with nondiabetic Wistar control. The T2DN rat displays a significant sexual dimorphism in insulin resistance, plasma cholesterol, renal and glomerular injury, urinary nephrin shedding, and albumin handling. Our results indicate that both male and female T2DN rats developed nonobese type 2 DKD phenotype, where the females had significant protection from the development of severe forms of DKD. Our findings provide further evidence for the T2DN rat strain's effectiveness for studying the multiple facets of DKD.

Keywords: diabetic kidney disease; diabetic nephropathy; nonobese; sex differences.

Publication types

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

MeSH terms

  • Albuminuria / metabolism
  • Animals
  • Biomarkers / urine
  • Blood Glucose / metabolism*
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetic Nephropathies / blood
  • Diabetic Nephropathies / diagnosis*
  • Diabetic Nephropathies / etiology
  • Disease Progression
  • Electrolytes / urine
  • Female
  • Glomerular Filtration Rate
  • Glucose Tolerance Test
  • Humans
  • Insulin Resistance
  • Kidney / metabolism*
  • Kidney / pathology
  • Kidney / physiopathology
  • Male
  • Metabolomics / methods
  • Rats, Wistar
  • Sex Factors


  • Biomarkers
  • Blood Glucose
  • Electrolytes