The effects of pregestational prediabetes as a risk factor for preeclampsia in pregnant female Sprague rats and the adverse effects of pregestational prediabetes on the placenta, liver and kidney function.

Abstract

Introduction Preeclampsia (PE) is a pregnancy complication that is diagnosed after 20 weeks of gestation with new onset hypertension and proteinuria. The risk factors of PE arise from trophoblastic and non-trophoblastic risk factors. The risk factors of PE include chronic hypertension, obesity and preexisting type 2 diabetes mellitus (T2DM). The onset of T2DM is preceded by PD and the prevalence of PD is increased exponentially in the developing countries due to urbanization, adapting to westernized diets that have high calories and normalized sedentary lifestyle. This westernized diet is associated with adverse effects on the heart, kidney and the liver. However, there are no reports of PD and its effects on pregnancy. In this study we investigated the effects of pregestational PD as a risk factor for PE in pregnant female Sprague rats and the adverse effects of maternal PD on the placenta, liver and kidney function. Methods Eighteen (18) female Sprague Dawley rats (150–180 g) were obtained from Biomedical Research Unit. High fat high carbohydrate (HFHC) with drinking water supplemented with fructose (HFHC+fructose) induced prediabetic female Sprague Dawley rats and LNAME induced preeclamptic female Sprague Dawley rats were used for this study. Parameters including non-fasting blood glucose concentration, body weights, blood pressure, fluid intake and urine output were monitored on gestational day (GND) 0, 9 and 18 during gestation period. Following sacrifice, parameters such as VEGF, PlGF, sFlt-1, NO, liver triglycerides, TNF α and liver function enzymes, lipid peroxidation, antioxidant status, kidney injury molecule (KIM 1), podcin, neprhin, creatinine, urea, albumin and electrolytes, were measured. Results The prediabetic group showed impaired non-fasting glucose, dyslipidemia, high blood pressure, impaired placenta function as evidenced by reduction in VEGF an PlGF and an increase in sFlt-1, impaired kidney function showed by increased plasma KIM-1, increased urinary podocin and nephrin and impaired electrolyte handling. The prediabetic group also showed impaired liver function as evidenced by increased plasma liver enzymes, increased liver oxidative stress and increased liver inflammation. Conclusion The diet-induced prediabetic rats showed impaired glucose handling and an imbalance in pro-angiogenic and antiangiogenic factors which lead to metabolic disturbances such as endothelial dysfunction, liver and kidney injury.