Effect of a High Fat Western Diet on the Progression of Diabetic Kidney Disease in Type 2 Diabetic Nephropathy (T2DN) Rats

Melissa Lowe, Ruslan Bohovyk, Christine A Klemens, Alexander Staruschenk

Diet influences the growing rate of obesity, increasing the risk of developing metabolic syndrome, leading to chronic illnesses such as diabetes. Diabetic Nephropathy (DN) is a complication of Type 2 Diabetes, prevalent in about 1 in 3 diabetics and is the primary cause of End-Stage Renal Disease (ESRD). The aim of this study was to assess how a high-fat Western diet impacts diabetic severity and disease progression during ESRD. We used aged (>38 weeks) male and female T2DN rats, an established non-obese type 2 diabetic animal model, and placed them on a normal (12 % NFD) or high (42% HFD) fat diet for 12 weeks, where urine and glucose tolerance tests (GTT) were assessed at weeks 0, 3, 6, 9, and 12. Food intake did not vary between diets, and the increase in total body weight on HFD was not significant by week 12 for both sexes. There were no significant differences in GTT curves or fasting blood glucose levels in females on either diet. In contrast, the HFD males’ fasting blood glucose levels and glucose concentrations increased progressively over the 12-weeks and became significantly different between the two groups by week 9 (204.5 ± 10.8 vs 284.4 ± 15.8 mg/dL, p=0.003, 370.4 ± 25.1 vs 457.5 ± 10.4 mg/dL, p=0.01 respectfully). The HFD did not affect urine output or kidney/total body weight ratios in both sexes, while heart weight/total body weight ratios in females were significantly reduced on the HFD (3.7 ± 0.1 vs 3.4 ± 0.1, p=0.03). Ongoing studies will quantify renal fibrosis, glomerular damage, albuminuria, lipidemia, and liver damage resulting from the HFD. In conclusion, the HFD appears to have a more deleterious effect on glucose handling in males than females; however, further studies are warranted to validate this effect.