Study Points To Mysteries Behind Type 2 Diabetes In Youth; Researchers Find Changes Of Puberty Initiate A Period Of Insulin Resistance Among Healthy Teen-Agers

Over the first few stages of puberty, cells in children’s bodies respond less and less to insulin, a natural hormone that—among other things—helps cells convert sugar from food into energy, the authors write in the November issue of the journal Diabetes.

"Puberty is a metabolically critical time," says Michael I. Goran, Ph.D., associate director of the USC Institute for Health Promotion and Disease Prevention Research and study co-author. "In a way, teenagers’ metabolism becomes rebellious, too."

Results of the study, the first to track sensitivity and response to insulin from childhood through young adulthood, carry implications for preventing type 2 diabetes during adolescence through steps such as diet and exercise. Doctors are diagnosing increasing numbers of young adults with type 2 diabetes, a significant health problem nationwide.

Insulin works in this way: Normally, after a meal, the body breaks down carbohydrates into glucose, or sugar, in the blood. That signals the pancreas to secrete insulin, because insulin helps the body’s cells pick up the glucose and convert it to energy. But when cells become resistant or less sensitive to insulin, as they do in type 2 diabetes, they cannot absorb glucose as well as they should and the sugar remains in the blood.

In healthy teens, insulin resistance disappears after puberty ends. Among people with type 2 diabetes, though, cells can ignore insulin more and more until they stop responding to insulin altogether.

The Diabetes study followed the development of 60 ethnically diverse children, beginning at about age nine. After two years, the children had progressed to various stages of puberty (measured by the appearance of sexual features).

Among those who reached the middle stage puberty, sensitivity to insulin dropped by 32 percent, report Goran, professor of preventive medicine at the Keck School, and Barbara Gower, Ph.D., assistant professor of nutrition sciences at UAB. Among those who did not yet show the signs of puberty, insulin sensitivity actually increased slightly.

Researchers found no link between insulin resistance and the release of sex hormones such as testosterone during puberty. Nor were gender, ethnicity or body fat implicated as causes for that insulin resistance.

Goran and Gower conclude that something about the changes of puberty—not simply aging—contributes to lowered sensitivity to insulin.

"The theory is that lowered sensitivity is a beneficial thing that switches on growth during puberty," Goran says. The tumultuous transformations and growth spurts of the teen years might naturally require the body to produce additional insulin to drive growth and tissue deposition.

When muscle and other cells become less sensitive to insulin, the pancreas’s beta cells (tiny insulin factories) usually respond by working harder to pump more insulin into the system, Goran explains. The sheer volume of insulin helps compensate for the body’s inefficient use of it.

Interestingly, though, the researchers found that in adolescents, beta cells do not produce as much insulin as expected to make up for insulin resistance. That might be a protective function, Goran says.

Here is why: In people with type 2 diabetes, beta cells appear to work harder and harder until they finally "wear out." In contrast, in healthy teens, beta cells might relax somewhat during adolescence so that when insulin sensitivity returns to normal at the end of puberty, the beta cells are vital and can keep working throughout adulthood. Teen-agers who do not recover their insulin sensitivity by adulthood, though, may end up with type 2 diabetes.

"In these teens, something makes them unable to recover," Goran says. "Something causes them to go beyond the threshold of insulin resistance that can be sustained and we need to continue tracking these children."

Scientists have noted that children today tend to start puberty at younger ages—likely linked to high body fat during childhood—and that might play a role in not recovering from teen-age insulin resistance at the end of puberty, he says. At younger ages, children’s bodies might not be ready to start a period of insulin resistance.

Further study also is needed to find out if puberty is lasting longer and if that longer duration might contribute, too.

When researchers determine the mechanisms for changes in insulin sensitivity during puberty, it may be important to find ways to ensure that insulin sensitivity recovers by the end of puberty and to protect beta cells. "More importantly, dietary and physical activity interventions should be explored for decreasing body fat, increasing insulin sensitivity and sustaining beta-cell function prior to and during pubertal development," Goran says.

The researchers will monitor children in the study throughout puberty to determine any factors associated with those who recover their insulin sensitivity and those who do not.

According to the American Diabetes Association, type 2 diabetes affects more than 15 million adult Americans. Complications may include early heart disease, kidney problems, vision loss and limb amputations. Cases are increasing in adults and children. As many as 85 percent of such children are overweight and most are diagnosed in middle-to-late puberty.

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The study was supported by the National Institute of Child Health and Development, the National Institute of Aging, and a General Clinical Research Center grant.

Michael I. Goran and Barbara A. Gower, "Longitudinal Study on Pubertal Insulin Resistance." Diabetes, Vol. 50, No. 11, November 2001.