Maternal Diabetes Causes Damage To Offspring's Beta Cell Functions

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Main Category: Diabetes
Also Included In: Biology / Biochemistry;  Pregnancy / Obstetrics;  Pediatrics / Children's Health
Article Date: 07 Mar 2008 - 0:00 PDT

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The link between a woman's maternal diabetes and her child's increased risk for diabetic complications is one step closer to being understood. According to recent research performed at the University if Louisville, there are many functional and metabolic changes that occur in such a child's pancreatic β cells, which could help explain this increased risk.

Maternal, or gestational, diabetes is a condition in which women previously undiagnosed with diabetes show high levels of blood glucose during pregnancy. It has been indicated previously that the occurrence of gestational diabetes increases the risk for many ailments in the woman's adult offspring, including obesity, glucose intolerance, and type 2 diabetes mellitus.

In contrast, type II diabetes is linked to a failure of the β cells of the pancreas to produce sufficient insulin. This affects many parts of the glucose metabolic pathway. The biochemical mechanisms behind these effects on the offspring of a woman who suffers from gestational diabetes are not well understood. In particular, this research set out to learn how diabetes during the period of gestation could influence the β cell function in the offspring, and thus potentially influence diabetes incidence.

To this end, Dr. Jianxiang Xu and Dr. Junying Han, of the Kosair Children's Hospital Research Institute, used a rat diabetes model to detail the mechanism. Diabetes was induced in female rats by the administration of streptozotocin (STZ) at the age of eight weeks, and once diagnosed, these females were mated with normal males. After delivery, the offspring were immediately transferred to normal foster mothers who had delivered other litters at the same time. This was done in order to prevent any potential effects caused by breast-feeding from a diabetic lactating mother. Additionally, a control group was established by administering a buffer solution without STZ.

When examined at birth, the birthweights of the pups was significantly decreased in the population from diabetic mothers, and the litter size was half of that of the control group. The premature death rate for the pups with diabetic mothers was 16%, while none of the control group showed mortality or health problems.

The β cell function of the offspring was analyzed at 15 weeks of age using various methods, both in vivo and in vitro, including blood titers and radioactive tracing. The resulting analysis showed:

• Insulin secretion ability, the primary function of the pancreatic β cells, was significantly impaired in both male and female pups. This includes a decrease of 40-50% when stimulated by glucose.
• Both glucose utilization and oxidation, two commonly used indexes for the metabolic function of pancreatic β cells, were reduced by 55% and 41% respectively. These results indicate that metabolic function of the cells was impaired. 
• Phosphofructokinase (PFK), pyruvate carboxylase (PC) and pyruvate dehydrogenase (PDH) levels decreased by 44-51%. All of these chemicals have important roles in the glucose metabolic pathway and indicate a disturbance in glucose levels as well as have an influence on insulin secretion. 

The authors postulate that the damage done to the β cells in the offspring of the diabetic group could have two potential causes. The first could be an increased level of free radical oxygen species during the diabetic pregnancy, as pancreatic β cells are especially sensitive to ROS. The second could be the abnormally high glucose levels the β cells experience during gestation -- this could prevent the upregulation of certain enzymes during pregnancy, making the β cells more susceptible to damage during the period of maternal diabetes.

They conclude that maternal diabetes can cause many disturbances in the metabolic and other functions of the pancreatic β cells of the offspring. These disturbances could contribute to later development of type 2 diabetes, and could hold many clues to the link between gestational diabetes and type II diabetes in humans.

Written by Anna Sophia McKenney
Copyright: Medical News Today
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