Studies of Diet Offer Little Insight to Preventing Pregnancy-Related Diabetes

April 29, 2008

April 29, 2009 (Newswise) — Many health care professionals suspect that a low glycemic diet may play a significant role in controlling pregnancy-related diabetes, but a recent review of evidence evaluating the effects of diet proved inconclusive.

One of the more troubling threats to a healthy, uncomplicated pregnancy is a metabolic disorder known as gestational diabetes mellitus. The condition affects an estimated 4 percent of mothers in the United States, and up to 14 percent worldwide. Pregnancy-related diabetes increases health risks for mothers and their babies, so researchers are searching for a means to prevent the disorder.

“The main implications of our research are suggestions for more high quality, long-term trials in healthy pregnant women, with larger sample sizes and reporting all clinically relevant outcomes, to address dietary issues more thoroughly and provide more conclusive results,” said lead review author Joanna Tieu.

“Our results suggest that a low glycemic index diet may be a benefit to mother and child, however,” said Tieu, at the Women and Children’s Hospital at the University of Adelaide in Australia.

“This is because low glycemic index diets — such as fresh fruits and vegetables and unprocessed whole-grain foods — tend to slow down the digestion of food. Slow digestion allows the body to better adjust to the load of sugar coming in after a meal,” she said.

“While our results were promising, the evidence is not sufficient to recommend changes in clinical practices, because of the limited number of trials,” Tieu said.

The review appears in the latest issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

The review authors found few clinical trials to include in their review. The three eligible studies included only 107 women living in the United States, Australia and the United Kingdom.

Doctors do not understand exactly what causes gestational diabetes, but they suspect that hormones from the placenta block the action of the mother’s insulin. Without enough insulin, sugar (glucose) cannot enter cells, where it is needed to fuel cell activity. Instead, sugars build up in the bloodstream, causing hyperglycemia.

These excess sugars and other nutrients flow through the placenta and into the baby’s cells, giving the baby more energy than it needs to develop. Stored as fat, these excess sugars may cause the baby to grow quite large — more than 8.8 pounds — or greater than the 90th percentile, compared to other babies.

A large baby may get wedged on the mother’s pubic bone during delivery, for example, putting the baby at risk for a number of health problems, including fractures or brachial plexus injuries, which can damage the network of nerves connecting the spine with the shoulder, arm and hand.

“Gestational diabetes also has been associated with spontaneous labor and premature birth,” Tieu said. “And children of women with gestational diabetes are at increased risk of obesity, glucose intolerance and diabetes in late adolescence and young adulthood.”

Mothers with gestational diabetes are at increased risk for preeclampsia (hypertension) or placental abruption during pregnancy. Induced births or Caesarean sections are more common, adding even more health risks. These women also have an increased risk of developing diabetes in the future.

Obstetrician Seth Brody, with Wake Medical Center in Raleigh, N.C., said that very large studies with longer follow-up are necessary to determine whether dietary changes can alter significant health outcomes. He suggests that in the future studies, researchers should go beyond simply knowing the difference in babies’ weights and serum glucose levels because these are not health outcomes of clinical significance.

“If the difference in birth weight were significant enough to be reflected as a difference in birth injury rates, Caesarean delivery rates and the need for operative deliveries, then that difference is of clinical importance, as is studying rates of brachia plexus injuries, fractures or neonatal mortality.” he said. “If a low glycemic diet altered the incidence of treatment for short- or long-term metabolic issues for either mom or baby, then those would be very important health outcome differences to determine, as well.

“At this point, it is most reasonable to continue to recommend the appropriate diet, weight gain, and exercise guidelines to all pregnant women, as outlined by the American College of Obstetrics and Gynecology,” Brody said.

The Cochrane Collaboration is an international non-profit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

American College of Obstetrics and Gynecology guidelines for pregnant women are available at http://www.acog.org

Tieu J, Crowther CA, Middleton P. Dietary advice in pregnancy for preventing gestational diabetes mellitus (Review). Cochrane Database of Systematic Reviews 2008, Issue 2.

Posted by dlife at 11:30 AM | Comments (0)

Kaiser Permanente Study Finds Diabetes Doubling Before Motherhood

April 27, 2008

April 27, 2008 (EurekAlert) - Diabetes before motherhood more than doubled in six years among teenage and adult women, according to a Kaiser Permanente study published in the May issue of Diabetes Care. http://care.diabetesjournals.org/

While previous studies have looked exclusively at gestational diabetes (diabetes that develops during pregnancy, then usually disappears after the baby is born), this is the largest and most diverse study to examine pre-pregnancy type 1 and type 2 diabetes, which is more dangerous than gestational diabetes and potentially harder to treat, as well as gestational diabetes.

Researchers at Kaiser Permanente’s Department of Research & Evaluation in Pasadena looked at 175,249 women who gave birth in 11 Kaiser Permanente hospitals in Southern California between 1999 and 2005. Researchers found that there were twice as many births to women with diabetes in 2005 as there were in 1999. Fifty-two percent of the women in the study were Hispanic, 26 percent were White, 11 percent were Asian/Pacific Islanders and 10 percent were African-American.

This study found significant jumps in pre-pregnancy diabetes in every age, racial and ethnic group:

* Diabetes increased fivefold among 13- to 19-year-olds giving birth

* Diabetes doubled among women 20- and 39-year-olds giving birth

* Diabetes increased by 40 percent among women 40 and older giving birth

* African-American, Hispanic, and Asian/Pacific Islander women were more likely to have diabetes before pregnancy than White women.

“More young women are entering their reproductive years with diabetes, in part due to the fact that our society has become more overweight and obese,” said lead author Jean M. Lawrence, ScD, MPH, MSSA, a research scientist at Kaiser Permanente’s Department of Research & Evaluation. “While we currently don’t know how to prevent type 1 diabetes, the steps to reducing risk of type 2 diabetes must start before childbearing years: healthy eating, active living and maintaining a healthy weight. These habits should begin in childhood and continue through adulthood.”

Given that two-thirds of Americans are overweight or obese, and nearly 15 million children are overweight or obese, these study findings are especially relevant.

The health risks of having diabetes before becoming pregnant are greater to mother and baby than gestational diabetes, which occurs in 8 percent of pregnancies. Gestational diabetes occurs when pregnancy triggers insulin resistance in the second trimester and raises a woman’s blood glucose level and is associated with larger babies, childhood obesity, and increased maternal risk of developing type 2 diabetes. Women with pre-existing diabetes are more likely to have miscarriages, stillbirths, and babies with birth defects because they may have elevated blood sugar during the critical first trimester of pregnancy when the infants’ organs are developing.

“My advice to women who have type 1 or type 2 diabetes and are thinking about becoming pregnant is: work with your health care professional to get your blood sugar in good control. If you are pre-diabetic or have type 2 diabetes and are overweight, work on reducing your weight by a few pounds before becoming pregnant,” Lawrence said. “And women with gestational diabetes should have their blood sugar level tested after they’ve given birth to make sure it returns to normal.”

Limiting obesity is the best way to reduce the rising incidence of type 2 diabetes in young women, says study co-author David Sacks, MD, a Kaiser Permanente perinatologist who specializes in maternal fetal medicine and treats up to 50 diabetic moms-to-be a year. “We’ve become a more sedentary and obese society so naturally type 2 diabetes has risen too. For Latina women, the risk is even higher for developing type 2 diabetes, so it’s really important to defy family history and work on achieving a healthy weight.”

Sacks said Kaiser Permanente’s electronic health record, Kaiser Permanente HealthConnect™, makes it easier for physicians to monitor and treat their patients’ diabetes.

“KP HealthConnect™ gives me an immediate record of my patient’s pre-pregnancy performance, and how compliant she has been with her diabetes protocol and follow-up,” Sacks said.

Posted by dlife at 10:19 AM | Comments (0)

First Research to Show That Diabetes Damages DNA in Men's Sperm and May Affect Fertility

May 03, 2007

May 3, 2007 (EurekAlert) - Scientists have found that sperm from diabetic men have greater levels of DNA damage than sperm from men who do not have the disease. They warn that such DNA damage might affect a man’s fertility.

In the first study [1] to compare the quality of DNA in sperm from diabetic and non-diabetic men, the researchers from Belfast, Northern Ireland showed that the DNA in the nuclei of the sperm cells had greater levels of fragmentation in diabetic men (52%, versus 32% in non-diabetic men), and that there were more deletions of DNA in the tiny, energy-generating structures in the cells called mitochondria (4 versus 3).

Dr Ishola Agbaje, who undertook the research published online today (Thursday 3 May) in the journal Human Reproduction, said: "As far as we know, this is the first report of the quality of DNA in the nucleus and mitochondria of sperm in diabetes. Our study identifies important evidence of increased DNA fragmentation of nuclear DNA and mitochondrial DNA deletions in sperm from diabetic men. These findings cause concern, as they may have implications for fertility."

The incidence of type 1 and type 2 diabetes is increasing rapidly worldwide. While diet and obesity are known to be key factors in the increase of type 2 (or late onset) diabetes, type 1 diabetes which is usually diagnosed in childhood or adolescence, is increasing by three per cent a year in European children, although the reason for this is not entirely clear. Genetic factors that make people more susceptible, or environmental factors such as viruses that may trigger the onset of type 1 diabetes, could play a role.

Dr Agbaje, a research fellow in the Reproductive Medicine Research Group at Queen’s University, Belfast, said: "If the increasing trend in the incidence of type I diabetes continues, this will result in a 50% increase over the next ten years. As a consequence, diabetes will affect many more men prior to and during their reproductive years. Infertility is already a major health problem in both the developed and developing world, with up to one in six couples requiring specialist investigation or treatment in order to conceive. Moreover, the last 50 years have seen an apparent decline in semen quality. Sperm disorders are thought to cause or contribute to infertility in 40-50% of infertile couples. The increasing incidence of systemic diseases such as diabetes may further exacerbate this decline in male fertility. However, it is not clear to what extent clinics consider information about the diabetic status of their patients when investigating fertility problems." [2]

Dr Agbaje and his colleagues examined sperm from 27 diabetic men, with an average age of 34, and 29 non-diabetic men with an average age of 33. They found that although semen volume was significantly less in diabetic men (2.6 versus 3.3 ml), there were no significant differences in sperm concentration, total sperm output, form and structure of the sperm or their ability to move. When they measured DNA damage they found that the percentage of fragmented nuclear DNA was significantly higher in sperm from the diabetic men and that the number of deletions in mitochondrial DNA was also higher – the number of deletions ranged from three to six (average four) in the diabetic men and from one to four (average three) in the non-diabetic men.

Professor Sheena Lewis, scientific director of the Reproductive Medicine Research Group, said: "Our study shows increased levels of sperm DNA damage in diabetic men. From a clinical perspective this is important, particularly given the overwhelming evidence that sperm DNA damage impairs male fertility and reproductive health. Other studies have already shown that, while the female egg has a limited ability to repair damaged sperm DNA, fragmentation beyond this threshold may result in increased rates of embryonic failure and pregnancy loss. In the context of spontaneous conception, sperm DNA quality has been found to be poorer in couples with a history of miscarriages."

However, Prof Lewis said that it was not possible to say from this current study whether the DNA damage caused by diabetes would have the same effect on men’s fertility and the health of future children as DNA damage caused by other factors such as smoking.

"This is just one, relatively small study that highlights a possible concern. Further studies need to be carried out in order to understand the precise nature of the diabetes-related damage, the causal mechanisms and the clinical significance. Given the global rise in the prevalence of diabetes, it is also vital to examine the reproductive outcomes of pregnancies fathered by diabetic men, and the prevalence of diabetes amongst men attending for infertility treatment," she concluded.

Posted by dlifenews at 09:11 AM | Comments (0)

Joslin Researchers Discover a Surprising Culprit in the Search for Causes of Diabetic Birth Defects

March 05, 2007

Protein Makes It Possible for High Blood Glucose to Enter Embryonic Cells

March 5, 2007 (EurekAlert) - Over the past several years, Joslin Investigator Mary R. Loeken, Ph.D., and her colleagues at Joslin Diabetes Center have unlocked several mysteries behind what puts women with diabetes more at risk of having a child with birth defects. Even though those risks have decreased significantly over the years, thanks in part to advancements at Joslin, women with diabetes still are two to five times more likely than the general population to have a baby with birth defects, especially of the heart and spinal cord, organs that form within the first few weeks of pregnancy.

In past work, Dr. Loeken and her research team were able to establish through their studies in mice that the mother's high blood glucose levels are the cause of these defects. This is one of the reasons why women with diabetes who are planning a pregnancy are encouraged to have their blood glucose levels under good control prior to conception. The Joslin researchers also have shown that the damage occurs because the extra glucose in the mother's blood inhibits the expression of embryonic genes that control essential developmental processes.

Now, in this latest study done in mice, Dr. Loeken and her colleagues have discovered that the protein called glucose transporter 2 (Glut2) makes it possible for the high concentrations of glucose to get into the embryonic cells efficiently when the mother's blood glucose concentrations are high. Also involved in the study was Rulin Li, Ph.D., a former postdoctoral fellow at Joslin. The study, supported by the National Institutes of Health, will appear in the March print edition of Diabetologia and was published online by the journal on Jan. 18.

"Glut2 is a gene that we wouldn't have expected to be switched on in early embryonic development," said Dr. Loeken, Investigator in the Section on Developmental and Stem Cell Biology and Associate Professor of Medicine at Harvard Medical School. "Yet our research in mice shows that the expression of this gene in the early embryo enables the cells to absorb glucose about two to three times faster when the mother's glucose levels are elevated, while other glucose transporters would be saturated at normal glucose concentrations. This makes the embryo very susceptible to the malformations that high glucose levels cause, such as neural tube defects."

Researchers so far have identified 14 different glucose transporters, a class of proteins that sit on the membranes of cells and enable the cells to absorb glucose. Each type plays a different role in glucose uptake and is found in different cell types. "We knew that the embryo expresses a variety of glucose transporters that bring necessary glucose into the developing cells," said Dr. Loeken, "but what caught my eye was that one of them was Glut2." This protein, Dr. Loeken explained, is what is known as a high-Km glucose transporter, that is, it works efficiently only when glucose levels are high. Low-Km glucose transporters, on the other hand, become saturated at these higher levels and no longer work efficiently to get glucose into the cells.

Low Km transporters can be thought of like a narrow doorway into a room that will only allow one person to pass at a time, whereas a high Km transporter is like a wide-open door that will allow several people to pass at a time, explained Dr. Loeken. When very few people need to get through the doors at a time, the narrow doors will work just as well as the wide-open doors, but if a crowd needs to get through the doors, the narrow doors will be saturated, the wide open doors will allow the people to go through at a high rate, and the concentration of people in the room will be very high.

"After birth, the Glut2 transporter is expressed on insulin-producing beta cells of the pancreas and in the liver, the tissues that receive blood carrying high concentrations of glucose absorbed from the intestine after a meal," said Dr. Loeken. "It makes sense that Glut2 would be expressed in the pancreas where the high glucose level signals the beta cells to release insulin, and in the liver, where it signals the liver to store the glucose. In a normal pregnancy, the glucose in the mother's blood that circulates to the uterus would never be as high as the blood that flows by the pancreas and the liver, and the embryo would not be exposed to high concentrations of glucose. Therefore, Glut2 won't work any better than the other glucose transporters to absorb glucose. But glucose concentrations can be very high during a diabetic pregnancy, and if this highly efficient glucose transport is functioning, the embryo cells act like a glucose sponge, absorbing glucose at a much higher rate than normal."

Using mice that lacked Glut2 genes, which were developed by one of the study's co-authors, Bernard Thorens, Ph.D., of the Center for Integrated Genomics at the University of Lausanne in Switzerland, Joslin researchers found that only embryos carrying normal Glut2 genes developed malformations when the mothers were diabetic, whereas embryos that lacked Glut2 genes were protected from malformations during diabetic pregnancy. "This shows that the high-transport Glut2 transporter was responsible for getting higher concentrations of glucose in the cell and causing the malformations." The embryos were examined on the 10th day of gestation. The time span in the mice, Dr. Loeken explained, is comparable to about the fourth or fifth weeks of a human pregnancy, which is about the time a woman may discover that she is pregnant.

The Joslin researchers were also surprised to find that there were fewer embryos recovered on day 10 of gestation if they lacked the Glut2 genes, whether or not the mothers were diabetic, suggesting that there is a survival advantage in having the Glut2 transporter. "Recent research by our collaborator, Dr. Thorens, has shown that Glut2 is also a transporter for glucosamine, an amino sugar that serves important functions in the synthesis of proteins," said Dr. Loeken. "Since glucosamine is synthesized in the liver, which the early embryo still lacks, it must get it from its mother's circulation. Although we don't know for sure, Glut2 could be needed by the embryo for glucosamine transport."

Putting these findings together, Dr. Loeken said, "The early embryo must express Glut2 for some reason, because fewer embryos survived early development if they lacked this transporter. Perhaps it is because it is needed to transport glucosamine. However, because this transporter, which works so well after birth to allow the pancreas to produce insulin and the liver to store glucose, also makes the early embryo take up glucose very efficiently when glucose concentrations are high, as can occur during diabetic pregnancy, this explains why the embryo is so sensitive to the mother's hyperglycemia.

"While it is too early yet to give any clinical recommendations to patients based on these new findings, the research does suggest that once the glucose reaches the concentration where the Glut2 transporter functions efficiently, that is probably sufficient to cause malformations," said Dr. Loeken. "The best we can do now to prevent malformations in diabetic pregnancy is to help a woman establish good blood glucose control before she becomes pregnant, so that she will be better able make sure her glucose levels are as close to normal during pregnancy," she added.

Posted by dlife at 01:51 PM | Comments (0)