(461) Gestational Diabetic Placental T-Cells cause hypertension and impaired glucose utilization in pregnant GDM rat model

Objective: Gestational diabetes mellitus (GDM) refers to glucose intolerance, insulin sensitivity and beta islet cell dysfunction during pregnancy. GDM pathogenesis is associated with hypertension, impaired placental and renal function, oxidative stress and increased circulating CD4+ T cells. Importantly, there are limited animal models available to study GDM or alternative treatment options. This study sought to determine if a possible mechanism for GDM is placental CD4+ T cell programming in the patient and to test alternative treatment options for GDM.

Study Design: Upon delivery, blood and placental GDM (GDM-CD4+ T cells) and normotensive (NP+NP) placental CD4+ T cells were collected. Purified CD4+T cells were injected into pregnant nude athymic rats on gestational day (GD) 12. On GD 13, a separate cohort rats were treated with Metformin (GDM+Met; 300 mg/kg/day) or MitoTempo (GDM+Mito;1 mg/kg/d). Mean arterial pressure (MAP), circulating glucose, and glucose tolerance tests (GTT) were performed on GD 19. Mitosox Red was used to measure mtROS production in HUVECs incubated with sera from GDM, GDM women treated with Metformin (GDM+Met) or Normotensive women. A one-way ANOVA was used for statistical analysis.

Results: MAP was higher in GDM-CD4+ T cell rats (121±2, n=8, p< 0.05) compared to GDM+MET (95±2, n=6), GDM+Mito (95±4, n=7), NP+NP CD4+ T cells (96±4, n=7), NP+NP MET (99±4, n=8), and NP nude controls (105±3 mmHg, n=8) rats. Blood glucose was elevated in GDM-CD4+ T cell rats (227±39 mg/dl, n=8, p< 0.05) compared to GDM+MET (111±11 mg/dl, n=7), GDM+Mito (97±2 mg/dl, n=7), NP+NP CD4+ T cells (89±3 mg/dl, n=7), NP+NP MET (96±2 mg/dl, n=8), and NP nude controls (82±9 mg/dl, n=8) rats. GTT was impaired in GDM CD4+ T rats, but was improved with Met and Mito treatment. Mitochondrial ROS was increased in HUVECS treated with GDM patient sera (p< 0.05) compared to GDM+Met or Normotensive patient sera.

Conclusion: Our findings indicate that GDM CD4+ T cells cause a diabetic phenotype suggesting a new model to investigate mechanisms and therapies.