Abstract P135: Effect Of A High Fat Western Diet On The Progression Of Diabetic Kidney Disease In Type 2 Diabetic Nephropathy (T2DN) Rats

Abstract

Diet influences the growing rate of obesity, increasing the risk of developing metabolic syndrome, which leads 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 DN during ESRD. We used aged (38+ wks) T2DN rats, an established DN model which has chronic kidney disease at this age and placed them on a normal (NFD) or high fat (42%, HFD) diet for 12 weeks. Previous studies revealed that T2DN males have more severe kidney injury progression. Thus, male (N=5-6) and female (N=6) rats were used to test effects of HFD in both sexes. Total food intake did not vary between diets. Urine and glucose tolerance tests (GTT) were assessed at weeks 0, 3, 6, 9, and 12. Both male (404.0 ± 10.2 vs 431.0 ± 7.1 g, p=0.053) and female (305.0 ± 14.4 vs 334.5 ± 17.6 g, p=0.22) T2DN rats gained weight on the HFD; however, the total body weights were not significantly different by week 12. Throughout the study, there were no significant differences in GTT curves or fasting blood glucose levels in females on NFD or HFD (wk 12: 123.3 ± 10.7 vs 149.3 ± 12.3 mg/dL, p=0.14). In contrast, the HFD males’ fasting blood glucose levels increased progressively over the 12-week period 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). Furthermore, at the 2 hr time point in the week 9 GTTs, male blood glucose concentrations were elevated compared to females (370.4 ± 25.1 vs 457.5 ± 10.4 mg/dL, p=0.01; and 222.7 ± 28.8 vs 205 ± 16.8 mg/dL, p=0.61, for male and female, respectively). The HFD did not affect urine volume output or kidney/total body weight ratios in males or females compared to their NFD counterparts. However, 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, glucosuria, lipidemia, and liver damage resulting from the HFD. In conclusion, the HFD seems to have a more deleterious effect on glucose handling in males than females; however, further studies are warranted to validate this effect.