Problems for Preemies: Early birth is linked to insulin overproduction

Infants born prematurely are more likely than full-term, normal-weight babies to later develop insulin resistance, a warning sign of diabetes, a new study finds.

A person with insulin resistance has cells that respond inefficiently to insulin, the hormone that orchestrates sugar metabolism throughout the body. By resisting the hormone’s effects, cells require the insulin-making pancreas to work harder, resulting in type 2, or adult-onset, diabetes. Over a lifetime, the insulin factories in the pancreas can wear out.

Earlier studies had shown that among full-term babies, significantly underweight newborns are more likely to develop insulin resistance at some time than normal-weight newborns are. Low birth weight stems from an adverse environment in the womb—typically, insufficient nourishment.

Scientists hypothesize that an undernourished fetus diverts scarce nutritional resources to the brain, thereby starving muscles and other tissues. This might permanently change the way cells in the body respond to insulin. The consequence would be bogged-down sugar metabolism.

In the new study, researchers identified 50 children ages 4 to 10 years who had been born prematurely but were in good health. They also enrolled 22 similar children who had been born full-term at normal weight and 12 who were born full-term but underweight.

Blood samples revealed that children born prematurely had more insulin resistance than the full-term, normal-weight kids did. Because of this, children born prematurely were making 50 percent more insulin than were the children of the same age born at normal weight, the researchers report in the Nov. 18 New England Journal of Medicine.

Children born full-term but underweight showed insulin resistance similar to that seen in the prematurely born children, says study coauthor Paul L. Hofman, a pediatric endocrinologist at the University of Auckland in New Zealand.

Notably, the children born prematurely had similar insulin resistance and insulin overproduction, regardless of whether their weight had been appropriate for their gestational age. The more underweight preemies probably had experienced more adversity during the first two trimesters of pregnancy, Hofman reasons. Nevertheless, in this study, that weight difference didn’t affect insulin resistance. Rather, the finding suggests that birth early in the third trimester disrupts a fetus’ “metabolic programming” for insulin use and sugar metabolism, he says.

“The third trimester appears to play a dominant role in setting insulin sensitivity,” Hofman says.

Many studies have linked low birth weight and premature birth to illnesses that strike later in life (SN: 12/9/00, p. 382: Weight Matters, Even in the Womb). Increased insulin resistance might be a key mechanism underlying that connection, since the condition also correlates with high blood pressure and heart disease.

By narrowing the vulnerable period to the third trimester of pregnancy, the scientists have come up with “a novel finding,” says Mark A. Sperling, a pediatric endocrinologist at the University of Pittsburgh School of Medicine.

While scientists work to elucidate the actual mechanisms that undermine normal insulin sensitivity, Sperling says, much can be accomplished by lessening premature births through better prenatal care. For the time being, gains in this area can therefore be achieved by policy changes and aren’t dependent on an improved understanding of metabolic programming, he says.