The Jerusalem Post

Diabetes during pregnancy is a warning sign for mother and fetus

- • By JUDY SIEGEL-ITZKOVICH

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.

LANDMARK STUDY BETTER PREDICTS STOMACH CANCER

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.

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