(P20-23-26) Dietary Resistant Starch Sustains Fasting GLP-1 Levels in Post-weaned and Pre-diabetic Male UCD-T2DM Rats

Objectives: Fermentable dietary fiber promotes gut microbial communities that produce SCFA associated with improved energy and glucose homeostasis. Most mechanistic studies supporting this derived from adult models, with limited models representing children or adolescents at risk for diabetes. This study aims to evaluate whether the addition of dietary resistant starch intake alters metabolic and intestinal parameters associated with insulin resistance and type 2 diabetes in post-weaned male UC Davis Type 2 Diabetes Mellitus (UCD‑T2DM) rats.

Methods: 24 pre-diabetic male UCD‑T2DM rats (59.1 ± 0.5 days old) were randomly assigned to receive ad libitum access to a standard chow diet (Teklad 2018S) diluted with either 20% digestible waxy-maize starch (DS, n=12) or 20% high amylose maize-resistant starch type 2 (DRS, n=12) for 4 weeks. Body weight and food intake were measured weekly. Fasting plasma glucose, insulin, GLP‑1, and non-fasting plasma glucose were measured prior to and after diet. Plasma glucose, insulin, and GLP-1 responses to an oral glucose tolerance test (OGTT) were also measured prior to and after diet. Intestinal permeability was measured using a fluorescein isothiocyanate (FITC)-dextran assay. Intestinal tissues for histological analysis, crypt depth, and villus height were measured across multiple intestinal regions.

Results: Body weight gain did not differ between DS and DRS groups across the 4-week diet; however, DRS rats exhibited a greater amount of food intake compared to DS rats. DRS rats had lower total energy intake relative to DS rats across the study period. Post-intervention plasma non-fasting glucose, fasting glucose, and insulin levels did not differ between dietary groups. Fasting plasma GLP-1 levels were statistically greater in DRS rats relative to DS rats. Plasma FITC-dextran time curves did not differ between DS and DRS groups, suggesting no differences in gut permeability. Furthermore, ileal villi heights and crypt depth showed no difference between the DS and DRS groups, nor did colonic crypt depth.

Conclusions: Additional dietary DRS intake sustains fasting GLP-1 levels but does not confer additional metabolic or gastrointestinal benefits in young male rats with a genetic propensity to develop insulin resistance and overt type 2 diabetes.

Funding Sources: NIH, USDA