Diabetes during pregnancy is a warning sign for mother and fetus

The latest in Israeli medical technology and research.

Pregnant woman  (illustrative)  (photo credit: INGIMAGE)
Pregnant woman (illustrative)
(photo credit: INGIMAGE)
Gestational diabetes, in which women suddenly develop high blood sugar levels during pregnancy, can have strange effects on the fetus, according to Prof. Asher Ornoy, an emeritus professor of pediatric neurology and child development at the Hebrew University’s Medical Faculty and long-time director of the teratology lab at Hadassah University Medical Center in Jerusalem.
Ornoy, who is the former director of the child development and rehabilitation department and the rehabilitation division of the Health Ministry, recently lectured on the subject at Ariel University’s Faculty of Health Sciences.
The various forms of diabetes involve genetic and environmental factors, and can affect embryonic development. A diabetic environment in the embryo causes changes in gene expression, such as insulin resistance, resulting in an increased risk of the mother, in her subsequent pregnancies and in the fetus developing diabetes. This may manifest itself in the child’s adolescence and later in metabolic syndrome (hypertension, diabetes, overweight and other metabolic changes) when he or she reaches adulthood.
Ornoy’s research is aimed at following the process in which the disease begins to develop. One of the reasons suggested is increased oxidative stress, because the fetus has no developed antioxidant system until it develops at the end of the pregnancy.
Increased oxidative stress due to high sugar can cause epigenetic changes, which are heritable changes in gene expression that do not involve changes to the underlying DNA sequence.
The prevalence of type-1 diabetes (“juvenile diabetes”) is about 0.5% to 1% in children, while, type-2 diabetes, usually caused by overweight, lack of physical activity and an unhealthful diet but also with genetic factors, is around 10% in adults. Type-2 diabetes is a global epidemic that has been intensifying in recent decades. Its development is linked to genetic and environmental factors and its manifestations in the decrease in the function of beta cells in the pancreas and insulin resistance.
In pregnant women in the third trimester, there is a tendency to suffer from gestational diabetes.
Untreated gestational diabetes poses a number of risks, including increased rate of miscarriage; intrauterine death, especially when labor is delayed; changes in fetal growth; complications near and immediately after birth; and increased incidence of developmental disorders, such as learning disabilities, ADHD and autism spectrum disorders (ASD).
When gestational diabetes is controlled with insulin and diet, the risks decrease.
Surprisingly, said Ornoy, in the presence of gestational diabetes, there is no increase in birth defects. The reason is that diabetes develops only in the second half of pregnancy, and most of the fetus’s vital organs have already developed. However, fetuses of mothers with gestational diabetes also exhibit complications near birth, involving high birth weight and developmental change because the brain develops throughout the pregnancy and is exposed to a potential effect of causing deformities due to gestational diabetes.
In his research, Ornoy examined school-age children born to mothers with gestational diabetes and compared them with children born to women with pre-gestational diabetes and no diabetes at all. It was found that maternal diabetes has no effect on intellectual ability.
On the other hand, it was found that the motor development of children to diabetes mothers was less good (especially their fine motor development), and that there was a higher incidence of ADHD regardless of type of diabetes.
This is because the brain develops throughout the pregnancy, and is exposed to a potential effect of causing deformities due to maternal diabetes.
The mechanism that explains many of these complications in fetuses is the high oxidative stress in the fetus in diabetes and the need for increased antioxidant activity. The body constantly produces free radicals and therefore may damage various parts of the cell, such as membranes, proteins and DNA.
Humans have a developed system of proteins and other substances that know how to neutralize free radicals. When too many free radicals are created, it is necessary to increase activity that neutralizes them, that is, antioxidant activity. The fetus has a hard time increasing the antioxidant activity and therefore various kinds of damages may occur due to increased oxidative stress.
Genomic technologies to better understand intestinal metaplasia (IM), a known risk factor for gastric cancer, have been developed by researchers at Duke University in North Carolina and NUS Yong Loo Lin School of Medicine in Singapore. The new findings offer the possibility of developing more effective screening for stomach cancer and timely and better early-stage treatments for patients.
The team, which published its findings in Cancer Cell, said that patients with IM are six times more likely to develop stomach cancer than those without. The discovery, they said, could also help detect infections with Helicobacter pylori bacteria, which are also linked to the disease.
Stomach cancer is the third deadliest cancer in the world according to World Health Organization statistics, but it is potentially treatable if detected early. Unfortunately, more than two-thirds of stomach cancer patients are only diagnosed at an advanced stage.
“Previous genetic studies on IM have mainly focused on patients who were already diagnosed with stomach cancer, but these are limited in their ability to predict who are likely to develop the disease and how the disease will progress,” said Prof. Patrick Tan, co-lead researcher at Duke who also works at the Singapore institution.
“Our study is the first to comprehensively map out the genetic changes in IM in a cohort of stomach cancer-free subjects, which helps us better predict the possible occurrence and progression of the disease.”
The researchers studied 3,000 patients in four hospitals in Singapore to show that a comprehensive analysis of the genetic patterns of IM can predict its subsequent progression towards stomach cancer. The genetic analysis of IM helps to identify those with a higher risk of progression to stomach cancer, adding further information to what is available by microscopic examination alone.