(PTFS12-05-23) Dietary Resistant Starch and a Low-Dose Renin-Angiotensin System Inhibitor Similarly Prevent Proteinuria and Maintain Vitamin D Status in a Preclinical Type 2 Diabetes Model

Objectives: Diabetic nephropathy is one of the most common complications of type 2 diabetes mellitus (T2D), and affects the kidney’s glomerular integrity. This leads to low circulating vitamin D levels, excessive urine protein excretion, and high blood pressure. Vitamin D deficiency in T2D contributes to insulin resistance, thereby exacerbating the progression of the disease. Previously, we observed that resistant starch (RS), a fermentable dietary fiber, improved protein and vitamin D homeostasis without affecting hyperglycemia, but the mechanistic basis remained unclear. The objective of this study was to determine whether dietary RS and low dose captopril, an ACE inhibitor used to manage hypertension, could be combined to better protect against diabetic kidney disease via the modulation of the renal renin-angiotensin system (RAS) in Zucker diabetic fatty (ZDF) rats, a preclinical obesity-related T2D model.

Methods: Lean control Zucker rats (n=8) were fed the AIN-93G diet containing corn starch and 0% RS and administered daily intraperitoneal (IP) placebo injections, while ZDF rats (n=48, 8 per group) were randomly assigned to one of the three diets (AIN-93G with cornstarch and 0% RS which served as control, 5% RS, or 10% RS) and daily IP injections of placebo or captopril for 8 weeks.

Results: The ZDF 10% RS captopril group showed a 63% decrease in total urinary protein creatinine ratio (P-value < 0.01), 30% reduction in albuminuria (p-value < 0.05), 47% reduction in urinary vitamin D binding protein (p-value < 0.05), and 47% reduction in urinary 25D (p-value < 0.05) when compared to the ZDF 0% RS placebo group. The 10% RS captopril group also exhibited a 62% increase in serum 25D levels (p-value < 0.05), while the 5% RS captopril group showed a 45% increase in serum 1,25D levels (p-value < 0.01) when compared to ZDF 0% RS placebo group.

Conclusions: Our results suggest that combination of RS and captopril, at low- to moderate doses, can attenuate proteinuria and vitamin D excretion and maintain circulating levels of serum vitamin D in T2D through modulating the activity of the RAS.

Funding Sources: Our research was funded by the USDA-NIFA program.