Sexual dimorphism in the progression of type 2 diabetic kidney disease in T2DN
Authors Spires DR, Palygin O, Levchenko V, Isaeva E, Klemens CA, Khedr S, Nikolaienko O,
Kriegel AJ, Cheng X, Yeo JY, Joe B, Staruschenko A
Submitted By Alexander Staruschenko on 5/5/2021
Status Published
Journal Physiological genomics
Year 2021
Date Published
Volume : Pages Not Specified : Not Specified
PubMed Reference 33870721
Abstract 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 non-obese type 2 diabetes model with the
spontaneous development of advanced diabetic nephropathy (T2DN rats). T2DN rats
at 12- and over 48-weeks 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 non-diabetic 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
non-obese 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.

Investigators with authorship
Alexander StaruschenkoMedical College of Wisconsin