Abstract 61: Cd4+t Cells Cause Hypertension, Increased Glucose, And Mitochondrial Dysfunction In A Novel Rodent Model Of Gestational Diabetes Mellitus

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Evangeline Deer ◽  
Jan Michael Williams ◽  
Lorena M Amaral ◽  
Sarah Fitzgerald ◽  
Owen Herrock ◽  
...  

Hypertensive (HTN) disorders of pregnancy increase risks for gestational diabetes mellitus (GDM) in pregnant women. GDM is characterized by hyperglycemia and β-cell dysfunction associated with increased inflammatory cytokines, oxidative stress, and activated CD4+ T cells. Streptozotocin (STZ) is used in nonpregnant rats to induce β-cell destruction causing features of diabetes. However, STZ is not ideal for pregnancy and leads to unsuccessful pregnancy outcomes, therefore other ways to establish animal models of GDM must be pursued. Previously, we showed CD4+T cells from a rat model of preeclampsia causes HTN and mitochondrial (mt) dysfunction/ROS compared to normal pregnant (NP) rats. Therefore, we hypothesize CD4+ T cells from a diabetic rat model could cause mt dysfunction/ROS and pancreatic β-islet cell destruction and lead to increased glucose and HTN during pregnancy. To examine our hypothesis, we adoptively transferred CD4+ T cells from STZ Dahl diabetic rats into pregnant Sprague Dawley (SD) rats and measured GDM features. Circulating CD4+ T cells were isolated from STZ induced diabetic Dahl virgin female rats and injected into pregnant SD rats on gestational day (GD) 12. On GD19, blood pressure (MAP) and tissues were collected and glucose levels were measured after 2h fasting in STZ CD4+ T cell recipients (GDM) and NP controls. Mt respiration and mtROS was measured in isolated mitochondria. On GD19, MAP increased to 105±0.5 mmHg (n=4, p<0.05) in GMD pregnant rats compared to control NP rats 91±2.1 mmHg (n=3). Blood glucose levels were elevated in GDM rats (139 ± 7 mg/dl, n=4, p<0.05) compared to NP controls (94 ± 1 mg/dl, n=3). Placental state 3 (26.4±5.9 vs 53.9±1.7 pmol/sec/mg, p<0.05) respiration rates, indicative of ATP production, was reduced in GDM rats (n=4) compared to NP controls (n=3). Placental mtROS was significantly increased in GDM rats (190 ± 27.1 % gated, n=3, p<0.05) compared to NP rats (100 ± 2.7 % gated, n=3). Collectively, the data indicate adoptive transfer of STZ CD4+ T cells causes increased circulating glucose, placental mt dysfunction and mtROS and HTN during pregnancy. These data demonstrate the importance of CD4+T cells in mechanisms causing the pathophysiology of GDM, and also introduces a potential novel animal model of GDM.

Author(s):  
Nina Meloncelli ◽  
Shelley A. Wilkinson ◽  
Susan de Jersey

AbstractGestational diabetes mellitus (GDM) is a common pregnancy disorder and the incidence is increasing worldwide. GDM is associated with adverse maternal outcomes which may be reduced with proper management. Lifestyle modification in the form of medical nutrition therapy and physical activity, as well as self-monitoring of blood glucose levels, is the cornerstone of GDM management. Inevitably, the search for the “ultimate” diet prescription has been ongoing. Identifying the amount and type of carbohydrate to maintain blood glucose levels below targets while balancing the nutritional requirements of pregnancy and achieving gestational weight gain within recommendations is challenging. Recent developments in the area of the gut microbiota and its impact on glycemic response add another layer of complexity to the success of medical nutrition therapy. This review critically explores the challenges to dietary prescription for GDM and why utopia may never be found.


2015 ◽  
Vol 7 (1) ◽  
Author(s):  
Gisele Seabra ◽  
Cláudia Saunders ◽  
Patrícia de Carvalho Padilha ◽  
Lenita Zajdenverg ◽  
Letícia Barbosa Gabriel da Silva ◽  
...  

2018 ◽  
Vol 47 (2) ◽  
pp. 754-764 ◽  
Author(s):  
Ebtisam A. Al-ofi ◽  
Hala H. Mosli ◽  
Kholoud A. Ghamri ◽  
Sarah M. Ghazali

Objectives The purpose of this study was to investigate the effect of remotely delivered telemedicine dietary advice on monitoring of blood glucose levels and weight gain of women with gestational diabetes mellitus (GDM). Methods Women with GDM were recruited and randomly allocated into two groups: a Tele-GDM group that received a telemonitoring device, and a control group that was followed-up traditionally. A telemonitoring service calculated the ratio of reaching or exceeding the pregnancy weight gain target (according to pre-pregnancy weight), following Institute of Medicine guidelines for healthy pregnancy weight gain. Results The sample comprised 27 women in the Tele-GDM group and 30 in the control group. At the end of pregnancy, the Tele-GDM group showed significantly lower 2-hour postprandial glucose levels than the control group. Most women in the Tele-GDM group reached their recommended range of weight gain at the end of pregnancy. Additionally, the Tele-GDM group showed significantly lower weight gain than the control group. Conclusions Telemonitoring can facilitate close monitoring of women with GDM and motivate patients to adopt a healthy lifestyle.


2019 ◽  
Vol 20 (6) ◽  
pp. 1408 ◽  
Author(s):  
Catalina Prieto ◽  
Bárbara Casas ◽  
Paulina Falcón ◽  
Andrea Villanueva ◽  
Pablo Lois ◽  
...  

Gestational diabetes mellitus (GDM) is a common metabolic disorder, defined by high blood glucose levels during pregnancy, which affects foetal and post-natal development. However, the cellular and molecular mechanisms of this detrimental condition are still poorly understood. A dysregulation in circulating angiogenic trophic factors, due to a dysfunction of the feto-placental unit, has been proposed to underlie GDM. But even the detailed study of canonical pro-angiogenic factors like vascular endothelial growth factor (VEGF) or basic Fibroblast Growth Factor (bFGF) has not been able to fully explain this detrimental condition during pregnancy. Netrins are non-canonical angiogenic ligands produced by the stroma have shown to be important in placental angiogenesis. In order to address the potential role of Netrin signalling in GDM, we tested the effect of Netrin-1, the most investigated member of the family, produced by Wharton’s Jelly Mesenchymal Stem Cells (WJ-MSC), on Human Umbilical Vein Endothelial Cells (HUVEC) angiogenesis. WJ-MSC and HUVEC primary cell cultures from either healthy or GDM pregnancies were exposed to physiological (5 mM) or high (25 mM) d-glucose. Our results reveal that Netrin-1 is secreted by WJ-MSC from healthy and GDM and both expression and secretion of the ligand do not change with distinct experimental glucose conditions. Noteworthy, the expression of its anti-angiogenic receptor UNC5b is reduced in GDM HUVEC compared with its expression in healthy HUVEC, accounting for an increased Netrin-1 signalling in these cells. Consistently, in healthy HUVEC, UNC5b overexpression induces cell retraction of the sprouting phenotype.


2019 ◽  
Vol 14 (1) ◽  
Author(s):  
Alexis Shub ◽  
Manisha Miranda ◽  
Harry M. Georgiou ◽  
Elizabeth A. McCarthy ◽  
Martha Lappas

Abstract Background We aimed to investigate the association of breastfeeding on postpartum glucose levels and lipid profiles in women diagnosed with gestational diabetes mellitus (GDM) and women without GDM. Methods We performed a secondary analysis of a cohort study of 243 women, 159 women with GDM and 84 normally glucose tolerant women between 2012 and 2017. At approximately 6–10 weeks postpartum, we measured fasting blood glucose and plasma lipid levels. Breastfeeding behaviour was self-defined as exclusive breastfeeding or not exclusive breastfeeding. Results The mean (SD) glucose in the group of women who breastfed exclusively was 4.6 (0.49) mmol/L, compared to 4.9 (0.58) mmol/L (95% CI 0.45, 0.15, p <  0.001) among women who did not exclusively breastfeed. Among women with GDM, the reduction in fasting glucose in women who were breastfeeding was 0.22 mmol/L (95% CI 0.39, 0.05, p = 0.004), and in women who were not GDM, the reduction was 0.14 mmol/L (95% CI 0.37, 0.09, p = 0.24,). After adjustment for GDM status in pregnancy, maternal body mass index (BMI), maternal age and ethnicity, and exclusive breastfeeding was associated with a decreased fasting glucose of 0.19 (95% CI 0.318, 0.061, p = 0.004). After similar adjustment, there was no significant difference in triglycerides, high density lipoprotein cholesterol or low-density lipoprotein cholesterol between women who were breastfeeding and women who were not breastfeeding. Conclusions Breastfeeding is associated with a reduction in fasting glucose levels postpartum, but not maternal lipid profile. Breastfeeding may play a role in reducing glucose intolerance in women who have had GDM.


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