Their insulin levels provided a clue. In the prenatally undernourished mice, the insulin secretion stayed about the same, regardless of the glucose level in the bloodstream. "That surprised us," Dr. Patti said. "The problem was not insulin resistance. It had something to do with insulin secretion." By contrast, babies who are born overweight (greater than 8 pounds) have higher risk of insulin resistance, not a secretion problem. Something different was happening in the experiment's low-birth-weight mice.
Did prenatal undernourishment cause the pancreas to not fully develop? 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."
Because studies of mice generally are good predictors of human biology, the Joslin study has 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.
"In particular, someone who was a low-birth-weight baby can compound the risk of developing diabetes by becoming overweight," she added. "The stage is set in two ways: low insulin production coupled with resistance to insulin -- a double whammy."
Source:Joslin Diabetes Center