Nutrition might affect fetal pancreas, mouse study suggests.

Poor nutrition in moms-to-be could set their child up for diabetes later in life, new research in mice suggests.

“Low birth weight is linked with abnormal function of the cells in the pancreas that make insulin,” explained lead researcher Dr. Mary-Elizabeth Patti, an assistant investigator at the Joslin Diabetes Center Research and an assistant professor of medicine at Harvard Medical School.

While experts have long noted an association between low birth weight and type 2 diabetes, this new research sheds light on why that may occur.

However, another expert cautioned that it’s difficult to draw parallels between the diets of mice used in this study and the nutrition of modern-day humans.

The findings appear in the March issue of Diabetes.

In their study, Patti’s team divided pregnant mice into two groups: One group ate as much as they wanted throughout their three-week pregnancy, while the other group was allowed to eat all they wanted only during the first two weeks of pregnancy, then had their food intake restricted during the third week of pregnancy.

Pups born to the second, calorie-restricted group weighed 23 percent less than the pups in the well-fed group, the researchers report. However, by three weeks of age, the mice pups all looked and acted the same, regardless of which group their mothers had been in.

Digging deeper, Patti’s group tested the pups’ blood sugar levels as they aged. They found that by two months of age both groups had similar blood sugar levels, but by four months mice that were in the low birth weight group displayed significantly higher blood glucose compared to their normal birth weight peers.

That gap continued to widen, the researchers add, so that by six months of age blood sugar levels in mice born undersized was abnormally high, reaching levels equivalent to those seen in diabetic humans.

In diabetics, poor blood sugar control comes from deficiencies in insulin secretion by the pancreas, or through cellular resistance to the effects of insulin circulating throughout the body.

The Boston team examined the mice’s pancreatic cells to determine which mechanism was at fault. They found that low birth weight mice born to mothers on poor diets had damaged cells in their pancreas that severely reduced the amount of insulin the mice could produce as they aged.

“One reason why people who have had a history of low birth weight are at increased risk for developing type 2 diabetes is that they’re not able to produce as much insulin as they should,” Patti speculated.

“If the nutritional environment that the baby is in during development is altered, that can affect the function of organs even during adult life - even though nutrition and everything has been normalized after birth,” she added.

According to the U.S. Centers for Disease Control and Prevention, the number of low birth weight babies in the United States increased 12 percent between 1980 and 2000. In 2002, 314,077 low birth weight babies were born - the highest level in over three decades. The CDC noted that part of this increase is due an increase in the number of multiple births, which are on the rise.

Anyone born undersized may be at an increased risk for type 2 diabetes as they age, Patti noted. “This study suggests that one important component of that risk for diabetes is the poor functioning of the insulin-producing cells in the pancreas,” she said.

She advised people who know they were low birth weight infants to take special care to keep their weight down and get plenty of exercise, since obesity is a prime risk factor for the type 2 diabetes. “Although the damage to the pancreas is permanent, it may not be a problem unless you gain weight or become physically inactive,” Patti said.

Dr. Rebecca Anne Simmons, an assistant professor of pediatrics from the University of Pennsylvania, said the findings may have limited applications for humans because, in her opinion, the calorie-restricted pregnant mice received nutrition far below what is seen in most humans.

“This is not similar to what we would observe in humans now. We don’t see that severe malnutrition,” she said.

Simmons also believes that any damage caused to the insulin-producing cells in the pancreas may occur because of decreased blood supply to the fetus, which restricts the flow of oxygen and other nutrients. “It is not due to malnutrition,” she contended.

SOURCES: Mary-Elizabeth Patti, M.D., assistant investigator, Joslin Diabetes Research Center, and assistant professor, medicine, Harvard Medical School, Boston; Rebecca Anne Simmons, M.D., assistant professor, pediatrics, University of Pennsylvania, Philadelphia; March 2005 Diabetes