In-utero Exposure to Maternal Diabetes Increase the Risk of Vascular Diseases in the F1 Offspring in Rats

Department of Biochemistry, Medical Research Institute, University of Alexandria, Egypt

*Corresponding author:

Maher A Kamel

Assistant Professor of Biochemistry

Medical Research Institute, Alexandria University

165- El Horreya Street

El Hadra, Alexandria

Egypt

Postal code: 21561

Tel: +2-01227151191

E-mail: maher.kamel@alexu.edu.eg

maherrashwan@hotmail.com

Abstract

Background: Maternal diabetes is one of the fundamental intrauterine disturbances that have direct and long lasting consequences on the health of the offspring. The risk for an individual to develop various vascular diseases throughout life is hypothesized to be related to diabetic gestation.

Aim: The present study aimed to evaluate the postnatal levels of different independent risk factors for vascular diseases including homocysteine (Hcy), nitric oxide (NO), lipid profile, glucose homeostasis and insulin resistance in the rat offspring of diabetic mothers. The effect of postnatal feeding with high caloric diet (HCD) was also assessed.

Methods: Two groups of female Wistar rats were used (diabetic and control); diabetes was neonatally induced by STZ injection to 5-day old rats. Pregnancy was induced by mating control or diabetic females with normal healthy males overnight and the pregnancies were completed to term. After delivery the offspring were weaned to control diet (CD) or high-caloric diet (HCD) (Table 1) and followed up for 30 weeks. So the offspring groups were as following: F1 offspring of control mothers under control diet (CF1-CD), F1 offspring of control mothers under HCD (CF1-HCD), F1 offspring of diabetic mothers under control diet (DF1-CD) and F1 offspring of diabetic mothers under HCD (DF1-HCD). Every 5 weeks 0.5 ml blood samples were obtained from the 20 male and female rats for assessment of fasting blood glucose, insulin, triglycerides, cholesterol (total, HDL-C and LDL-C), homocysteine and nitric oxide end products (NOx).

Results: The results indicated that maternal diabetes caused an age-dependent alteration in glucose homeostasis and resulted in insulin resistance especially in male offspring. Also, lipid profile showed elevation of triglycerides, cholesterol and LDL-C while HDL-C showed significant decline in the offspring of diabetic mothers. These disturbances in glucose and lipid metabolism were associated with elevated plasma level of Hcy from 25 week age and thereafter. Also, there was an elevation in the level of nitric oxide end products (NOx).

Conclusion: Maternal diabetes cause increased risk for vascular diseases in the offspring. The mechanisms of this predisposition involve disturbed lipid profile, insulin resistance, increased circulatory levels of Hcy (independent risk factor for vascular diseases) and nitric oxide end products. Male rat offspring appear to be more sensitive for the development of vascular diseases than female offspring and postnatal diet plays important role in this predisposition as the risk increases with high caloric diet.

Keywords: Fetal origin of disease, Diabetes, homocysteine, cardiovascular, Nitric oxide.

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