Obesity, Insulin Resistance and Diabetes: A Definite Connection
Children who are insulin resistant and obese are far more likely to develop diabetes than those who aren't, according to a new study led by David Klein,MD, PhD, and John Morrison, PhD.* "The important word is 'and,' because there seems to be an independent relationship between insulin resistance and diabetes, and also between obesity and diabetes. Now we're learning how they interact," says lead author Dr. Klein, of the Division of Endocrinology at Cincinnati Children's.
"This study is the first time that longitudinal data have revealed that early obesity and insulin resistance are associated with the development of type 2 diabetes by age 18," explains corresponding author Dr. Morrison, of the Division of Cardiology. He notes that a longitudinal study provides more solid proof than a retrospective study and is more difficult to complete.
A 10-Year Cohort Study
The research drew on the National Heart, Lung and Blood Institute Growth and Health Study, a 10-year cohort study of the development of obesity in black and white girls, for which Dr. Morrison was principal investigator for the first nine years. To examine the relationships of obesity with insulin resistance and increased glucose in adolescent girls, fasting insulin and glucose levels were measured at baseline (ages 9 and 10 years) and a decade later. At the end of 10 years, more than 80 percent of the original participants remained in the cohort.
Before puberty began, there was no significant difference in obesity between the black and white girls. "However, during their teens, black girls tended to become more overweight," Dr. Morrison explains. The 10-year incidence of obesity was 2-1/2 times greater in black than white girls. "We also showed that black girls were more insulin resistant when the study started and 10 years later, leading to a greater likelihood of developing diabetes." In fact, at the study's end, seven girls -- all black -- had glucose values consistent with diabetes.
This is a key finding, according to Dr. Klein. "Before, scientists tried to infer what we have now shown: that black girls are more insulin resistant before puberty than white girls. Body Mass Index (BMI) at ages 9 and 10 in blacks is an important determinant of fasting glucose levels and the risk for impaired fasting glucose 10 years later." He notes that with every incremental increase in BMI, insulin resistance increased, verifying a well-known fact. Conversely, if an overweight girl (either black or white) ceased being overweight, her insulin sensitivity also decreased.
Focus on the Environment
In contrast, the researchers found that in white girls, the rate of increase in BMI during the 10-year period was more important in predicting fasting glucose levels and the risk for impaired fasting glucose 10 years later.
To confirm these findings, the researchers hope to do a second study, and they point out that more epidemiological studies are needed on determinants for diabetes."To combat the rising incidence of diabetes,we need to develop a specific genetic test that can be used early to help identify those at risk and prevent it. We need to identify the ethnic differences in gene polymorphisms that influence insulin sensitivity or insulin production or metabolism. Our study helps to target the course of this genetic research. And eventually,we'll need to institute some global changes in the environment," Dr. Klein says.
He notes that the risk of developing diabetes depends 30 percent on genetic factors and 70 percent on environmental factors."We know there hasn't been an increase in defective genes over the last 20 years. What's changed is the environment that the genes live in," Dr. Morrison says. To begin to make those environmental changes, both researchers currently are developing a school program in which senior high school students will counsel middle school students on healthy choices.
For now, Dr. Klein recommends that pediatricians identify early risk factors for diabetes in their patients: a family history of type 2 diabetes and the development of obesity in childhood. With that knowledge, they can encourage patients and their families to make needed changes to help to prevent diabetes from developing.
Dr. Klein is associate professor of pediatrics in the Division of Endocrinology at Cincinnati Children's, and Dr. Morrison is associate professor of pediatrics (research) in the Division of Cardiology. Their study was published in Diabetes Care (27[2]:378-383, 2004 February) and was supported by grants from the National Institutes of Health.
