Obesity, physical inactivity, genetics and age have long been recognized as risk factors for developing high blood glucose and diabetes. But over the past few years, scientists have discovered another risk - low birth weight. Now in a study with mice, Joslin Diabetes Center researchers have shown how it might be possible for people who were low weight at birth to protect themselves.
"We wanted to see if eating a controlled diet and stopping weight gain would prevent the development of glucose intolerance," explains Mary-Elizabeth Patti, M.D., Investigator in Joslin's Research Section on Cellular and Molecular Physiology and Assistant Professor of Medicine at Harvard Medical School, the study's co-author. Former Joslin fellow Marcelino Hernandez-Valencia, M.D., collaborated with Dr. Patti on the study.
This talk is among 89 presentations Joslin scientists will deliver at the 65th Annual Scientific Sessions of the American Diabetes Association, starting today, Friday, June 10, through Tuesday, June 14, at the San Diego Convention Center. Some 13,000 scientists, physicians and health professionals from around the world will attend the conference. The talk is scheduled to be delivered today, Friday, June 10, in a 4:15-6:15 p.m. PST session on Regulation of Food Intake and Body Weight. (Abstract Number 49-OR: "Thin Phenotype Protective for Impaired Glucose Tolerance Related to Low Birth Weight").
To test their strategy, the Joslin scientists bred two different groups of mice: the control group whose mothers were allowed to eat as much as they wanted during pregnancy, and a second group whose mothers' diets during pregnancy were restricted to only half that amount. At birth, the offspring of mice with undernourished mothers weighed about 25 percent less than the offspring of the well-nourished mice. For the next phase of the experiment, the researchers further divided both control and low-birth weight mice into two subgroups. In one of the subgroups, the mice were allowed to eat freely. The mice in the other set, however, were kept on calorie-restricted diets.
After two weeks, the low birth weight offspring who were allowed to eat at will had caught up in weight to the mice with well-nourished mothers, a finding consistent with human data over a comparable life span. At age 4 months, body weight was similar in all four groups, and at six months, the mice on restricted diets weighed only a little less (about 5 percent) than the mice in the other groups.
As the mice matured, the scientists also monitored their glucose levels. Over time, they began to see a difference. At age 2 months, the test results were identical among all four groups. But by age 6 months, the free-eating, low birth weight mice began to show signs of glucose intolerance. The low birth weight mice on a controlled diet, however, didn't have this problem: their blood glucose levels were identical to the mice in the control groups whose weight at birth was normal.
"Our data suggest that staying thin is an effective way to avoid developing glucose intolerance and diabetes for people who had a low birth weight," says Dr. Patti. "Preventing obesity enables the diet-controlled low birth weight mice to respond better to insulin. Of course, we will need careful studies to assess how these finding relate to humans and how we can use them to optimize nutrition in children with a history of low birth weight."
According to the Centers for Disease Control and Prevention (CDC), the incidence of low birth weight babies weighing less than 2500 grams (5 1/2 pounds) in the U.S. increased 12 percent between 1980 and 2000, while the rate of babies weighing less than 1500 grams (3 1/3 pounds or less), is up 24 percent. The CDC reports that 314,077 low birth weight babies were born in 2002, representing 7.8 percent of the births that year, the highest level reported in more than three decades. This is due in part to an increase in the number of multiple births, which also are on the rise.
"Poor fetal growth is a serious problem that can occur in many ways other than inadequate nutrition of the mother," says Dr. Patti. "Now we have a strategy that might help individuals with a history of low birth weight reduce their risks of developing this very serious disease."