(P10-084-24) Feasibility of Using the UC Davis Type 2 Diabetes Mellitus Rat Model as a Preclinical Model of Gestational Glycemic Dysregulation

Objectives: Preclinical models of gestational glucose dysregulation are limited due to the protective effect of female sex hormones on key metabolic tissues. Our objective is to determine whether the consumption of a 15% sugar solution can induce gestational hyperglycemia in UC Davis Type 2 Diabetes Mellitus (UCDT2DM) rats, which have a polygenic origin of diabetes.

Methods: Female UCDT2DM rats (57.0 ± 8.8 days old) were provided ad libitum access to either 0% (control; n=6) or 15% sugar solution (19.5% high fructose corn syrup mixed with drinking water w/w; n=7) 2 weeks prior to mating and throughout pregnancy. Female rats were mated with non-diabetic male rats (~60.0 days old) and confirmation of pregnancy was determined by vaginal plug. Pregnant dams were euthanized at dpc 18.5 and fetal weights were collected. Non-fasting plasma glucose was measured with a glucometer at dpc 0.5, 7.5, 14.5, and 18.5. Oral glucose tolerance tests (OGTT) were conducted at dpc -2 and 17.5. Plasma glucose and insulin from OGTTs were measured with an enzymatic assay and electrochemiluminescent immunoassay, respectively.

Results: Total energy intake in was greater in rats consuming added sugar relative to controls; driven by a significant increase in liquid intake. Percent change in body weight trended higher in sugar treated dams (P = 0.056); however, within day assessment showed no difference between groups. Similarly, non-fasting glucose levels were greater in rats consuming added sugar compared to controls (P < 0.01), but not different between groups in within time analyses. OGTT glucose curves were not different between sugar and control groups before or during pregnancy. Glucose curves at dpc 17.5 were significantly reduced in both groups compared to dpc -2. OGTT insulin curves were significantly elevated in both groups at dpc 17.5, however, rats consuming added sugar had 53% greater mean peak insulin levels compared to controls (P < 0.01). No difference in fetal weights were detected between groups when controlling for dam and litter size.

Conclusions: A 15% addition of added sugar in drinking water led to gestational insulin resistance in UCDT2DM rats, but was not sufficient to induce gestational hyperglycemica. Additional studies are needed to determine whether the UCDT2DM Rat Model can be used as a polygenic model of glycemic glucose dysregulation.

Funding Sources: USDA-ARS