Obesity is not a universal phenotype in children with type 2 diabetes (T2D), a global systematic review and meta-analysis reported. In fact, the study found, as many as one in four children with T2D do not have obesity and some have normal reference-range body mass measurements. Further studies should consider other mechanisms beyond obesity in the genesis of pediatric diabetes, the authors of the international analysis concluded, writing for JAMA Network Open.
“We were aware that some children and adolescents with T2D did not have obesity, but we didn’t know the scale of obesity in T2D, or what variables may impact the occurrence of diabetes in this group,” endocrinologist M. Constantine Samaan, MD, MSc, associate professor of pediatrics at McMaster University in Hamilton, Ont., told this news organization. “So, the analysis did help us understand the body mass distribution of this group in more detail.”
Dr. M. Constantine Samaan
The international investigators included in their meta-analysis 53 articles with 8,942 participants from multiple world regions and races/ethnicities. The overall prevalence of obesity in pediatric patients with T2D was 75.27% (95% confidence interval [CI], 70.47%-79.78%). The prevalence of obesity at time of diagnosis in 4,688 participants was 77.24% (95% CI, 70.55%-83.34%). Male participants had higher odds of obesity than females: odds ratio, 2.10 (95% CI, 1.33-3.31) – although girls are generally more likely to develop T2D. The highest prevalence of obesity occurred in Whites at 89.86% (95% CI, 71.50%-99.74%), while prevalence was lowest in Asian participants at 64.50% (95% CI, 53.28%-74.99%).
The authors noted that childhood obesity affects approximately 340 million children worldwide and is a major driver of pediatric T2D, an aggressive disease with a high treatment failure rate. Understanding the contribution of body mass to the evolution of insulin resistance, glucose intolerance, and T2D with its attendant comorbidities and complications, such as nonalcoholic fatty liver disease, remains crucial for developing personalized interventions.
Known risk factors for T2D include interactions between genetics and the environment, including lifestyle factors such as diet and low physical activity levels, Dr. Samaan noted. Certain ethnic groups have higher T2D risks, as do babies exposed in the womb to maternal obesity or diabetes, he said. “And there are likely many other factors that contribute to the risk of T2D, though these remain to be defined.”
Is “lean” T2D in children without obesity likely then to be hereditary, more severe, and harder to control with lifestyle modification? “That’s a great question, but the answer is we don’t know,” Dr. Samaan said.
Commenting on the study but not involved in it, Timothy J. Joos, MD, a pediatrician in Seattle affiliated with the Swedish Medical Center, said the findings raise the question of how many pediatric T2D patients are being missed because they don’t meet current screening criteria. “In nonobese T2D pediatric patients, genetics (and by proxy family history) obviously play a heavier role. In my practice, I often get parents asking me to screen their skinny teenager for diabetes because of diabetes in a family member. In the past I would begrudgingly comply with a smirk on my face. Now the smirk will be gone.”
Dr. Joos said it would be interesting to see what percentage of these T2D patients without obesity (body mass index < 95th percentile) would still meet the criteria for being overweight (BMI > 85th percentile) as this is the primary criterion for screening according to the American Diabetes Association guidelines.
Current guidelines generally look for elevated body mass measures as a main screening indication, Dr. Samaan’s group noted. But in their view, while factors such as ethnicity and in utero exposure to diabetes are already used in combination with BMI-based measures to justify screening, more sophisticated prediabetes and diabetes prediction models are needed to support a more comprehensive screening approach.
“Because being overweight is the initial criterion, children with multiple other criteria are not being screened,” Dr. Joos said. He agreed that more research is needed to sort out the other risk factors for pediatric T2D without obesity so these patients may be detected earlier.
New models may need to incorporate lifestyle factors, hormones, puberty, growth, and sex as well, the authors wrote. Markers of insulin resistance, insulin production capacity, and other markers are needed to refine the identification of those who should be screened.
Dr. Samaan’s group is planning to study the findings in more detail to clarify the effect of body mass on the comorbidities and complications of pediatric T2D.
In addition to the study limitation of significant interstudy heterogeneity, the authors acknowledged varying degrees of glycemic control and dyslipidemia among participants.
No specific funding was provided for this review and meta-analysis. The authors disclosed no conflicts of interest. Dr. Joos disclosed no competing interests with regard to his comments.