News Article
Beta-Cell Abnormalities Herald Signs of Type 2 Diabetes Risk in Obese Teens
LOS ANGELES (EGMN) - Impaired beta-cell function appears to be one of the earliest signs of type 2 diabetes risk in obese adolescents, according to a study of 60 obese but otherwise healthy teens.
Fourteen (23%) of the teens had a progressive decline in insulin sensitivity and developed impaired glucose tolerance over a 3-year period. All 14 of these teenagers had manifested primary defects on beta-cell function at study entry, despite having normal glucose tolerance, said Dr. Sonia Caprio, professor of pediatrics at Yale University, New Haven, Conn.
"The progressive decline in insulin sensitivity further aggravates beta-cell function, thus contributing to the worsening of glucose tolerance. Prevention of type 2 diabetes mellitus in obese youth should start very early and target both insulin resistance and beta-cell dysfunction," Dr. Caprio said at the 6th World Congress on the Insulin Resistance Syndrome.
Working in collaboration with Claudio Cobelli, Ph.D., of Padua (Italy) University, Dr. Caprio followed the obese teens from the Yale Pediatric Obesity Clinic and measured their glucose tolerance using the oral glucose tolerance test (OGTT) at three time points over a 3-year period. Her aim was to see whether she could discover the earliest signs of incipient type 2 diabetes.
The OGTT was normal in all participants at baseline. However, at year 2, when the second OGTT was performed, 14 of the participants had started to show signs of impaired glucose tolerance. At the third OGTT, these patients had progressed to impaired glucose tolerance.
The progressors all had impaired beta-cell function at baseline. By the second OGTT, pancreatic function had decreased and continued to get progressively worse.
The demographics of both progressors and nonprogressors were similar with regard to gender, age (median 12 years), and body mass index. More nonprogressors had a family history of type 2 diabetes than did progressors (36% vs. 29%), Dr. Caprio said.
"This is the first time that we are showing that the reason for developing insulin resistance is because of impaired beta cells," Dr. Caprio said.
In addition to impaired glucose tolerance and beta-cell dysfunction, teens who were headed for type 2 diabetes deposited more fat in their liver and muscles.
"There are differences in the prediabetes forms already in children. I want to emphasize that there is an evolution that gradually takes place. They go from normal glucose tolerance to impaired glucose tolerance and there are two defects, both insulin resistance and early defects in pancreatic beta-cell function," Dr. Caprio said.
The study did not continue to follow the teens to see who would eventually get full-blown diabetes.
But, Dr. Caprio warned, "If these children do not improve their weight or physical activity - or in extreme cases, be put on medication - they are at very high risk for developing type 2 diabetes."
Dr. Caprio said she was pleased to see that most of the obese teens did not develop glucose intolerance. "Twenty-three percent of the original cohort moved from normal glucose tolerance to impaired glucose tolerance, but the rest remained normal. So it's quite nice ... they had excellent tests, the same plasma glucose every time we repeated those tests. These teens kept their normal glucose tolerance as opposed to those who were developing prediabetes."
Why do some go on to develop impaired glucose tolerance, while most do not?
Dr. Caprio said she would like to find the answer to that question. "We need to understand why they already have the predisposition to prediabetes, and how we can reverse or prevent it."
In the meantime, prevention of type 2 diabetes in at-risk youth should target insulin resistance and beta-cell dysfunction "as early as possible," she said.
Dr. Caprio said she had no conflicts of interest to disclose.
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