How prenatal diet can raise risk of diabetes in offspring
insulin-producing cells in the pancreas, which could explain why
babies that weigh less at birth are at higher risk of diabetes, say
researchers.
A team at the Joslin Diabetes Center affiliated with Harvard Medical School has demonstrated that the offspring of undernourished mice develop the equivalent to full-blown diabetes, despite developing normally in the first months of life.
"The bottom line is that if you don't have delivery of enough nutrients from the mother to the baby, the baby's pancreatic cells will be programmed abnormally," said principal investigator Dr Mary-Elizabeth Patti.
"The effect doesn't show up until later on - usually not until adolescence or adulthood."
She added: "Many people believe we don't have much of a prenatal nourishment problem in the United States. But poor nutrition of a developing baby can occur in many ways other than inadequate nutrition of the mother. It also can occur with abnormal development of the placenta and its blood vessels, or high blood pressure, which damages vessels."
The study, published in the March edition of Diabetes, reinforces findings from previous research that has shown that infants with low birth weight - under 5.5 pounds - have a higher risk for developing type 2 diabetes.
The researchers separated pregnant mice into two groups. The control group ate as much chow as they wanted during the entire pregnancy while the others were fully nourished during the first two weeks of pregnancy but undernourished during the third week, restricted to only half the amount.
Restricted nutrition had a dramatic effect on this group - their babies weighed 23 per cent less than the control group.
After delivery, all mothers ate a full diet, and by the time the babies were weaned at three weeks, the low-birth-weight group had caught up with the others, "something we see in human babies too," said Dr Patti.
The two groups of offspring ate the same chow diet, and neither group was allowed to become overweight, eliminating this common risk factor for diabetes.
However as the young mice matured, differences began to unfold. When four months old (comparable to human adolescence), the low-birth-weight babies began showing higher levels of blood glucose.
"By six months, these levels had spiked abnormally, to 500 mg/dl - the equivalent of serious, full-blown diabetes in humans," Dr Patti said.
Normally, insulin levels rise or drop in response to glucose levels, keeping everything in balance. But in type 2 diabetes either the pancreas does not make enough insulin or the body's cells develop a resistance to its effect, causing the spike in blood glucose.
In the mice study, researchers found that insulin secretion in the prenatally undernourished mice stayed about the same, regardless of the glucose level in the bloodstream.
"That surprised us," Dr Patti said. However this means that the problem was not insulin resistance, but rather something to do with insulin secretion.
The researchers found no difference in pancreas size or numbers of pancreatic beta cells, which produce insulin. But cultures of the beta cells revealed the answer: the undernourished mice had an abnormal way of responding to glucose.
"They were somehow 'programmed' to secrete a limited amount of insulin later in life, no matter what signal they got from glucose," Dr Patti said. "The impairment was permanent. It couldn't be corrected even when the body caught up to normal weight."
Mice are considered good predictors of human biology, say the researchers, giving their study important implications.
"People and their doctors need to understand that prenatal undernourishment makes a person permanently at higher risk for developing diabetes, so prenatal care is important," Dr Patti said. "Moreover, if someone was born with low weight, they need to pay special attention to prevention tactics, including exercise and weight control to minimize insulin resistance - the other major factor involved in triggering type 2 diabetes."
She added that someone who was a low-birth-weight baby can compound the risk of developing diabetes by becoming overweight. "The stage is set in two ways: low insulin production coupled with resistance to insulin - a double whammy."
