Pediatric Liver Disease in Children Linked With a High Risk for T2D, Study Finds

Children with nonalcoholic fatty liver disease (NAFLD) have a higher risk for type 2 diabetes (T2D), according to a study published in Clinical Gastroenterology and Hepatology.

T2D was not only found in children at baseline, they were also more likely to have it by the end of the study.

The findings, the authors said, suggest that further work is needed to “identify both lifestyle and potential medication strategies to prevent the development of these dual diagnoses that may have synergistic negative implications on long-term health.”

A cohort of 892 children with NAFLD enrolled in the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN) between 2004 and 2017 from 15 pediatric centers across the United States; they were followed for an average of 4 years to evaluate the incidence of T2D.

Upon initial assessment, T2D was already present in 6.6% of children..

The study found that children with NAFLD who did not enter the study with T2D had developed it by the end of the follow-up period. The incidence rate of T2D was 3000 cases per 100,000 person-years, producing an annual incidence rate of 3% in children enrolled in NASH CRN.

The incidence rate of T2D in children with NAFLD was found to be 30 times greater than previously reported in other pediatric populations at increased risk for T2D related to overweight/obesity status and/or race or ethnicity.

This high incidence suggests that a diagnosis of NAFLD identifies children at a particularly increased risk for developing T2D.

Severity of NAFLD was independently associated with increased risk of incident T2D, indicating that the variation in incidence was not sufficiently explained by confounding factors of race, ethnicity, or obesity.

Of the participants with T2D, 60% developed NAFLD prior to the development of diabetes. However, the sequence of events determining whether NAFLD or T2D develops first is unclear.

Severity of liver histology at the time of diagnosis was independently associated with T2D development, and severity of hepatic histology at baseline in children with NAFLD without T2D was also found to be a significant risk factor for subsequent T2D.

Additional risk factors shown to be associated with increased risk of incident T2D were female sex, older age, and higher BMI z-score.

The study concluded that children with NAFLD represent a high-risk group for both existing and incident T2D, indicating that children with NAFLD should be closely monitored for T2D development.

“Targeted prevention strategies of T2D development in children with NAFLD are urgently required,” wrote the authors.

T2D is known to impact morbidity and mortality in adults with NAFLD, but these impacts have yet to be assessed in children.

“We need to better understand how NAFLD contributes to type 2 diabetes risk in children so that we can actively work to prevent it,” Jeffrey Schwimmer, MD, professor of pediatrics at University of California San Diego School of Medicine and director of the Fatty Liver Clinic at Rady Children’s Hospital-San Diego, said in a statement.

The study faced some limitations. There was only a single measure of glucose level each year. Markers used for classification of T2D may underestimate diabetes in children. Additionally, there was some loss to follow-up of study participants over time.

Reference

Newton KP, Wilson L, Crimmins NA, et al; the Nonalcoholic Steatohepatitis Clinical Research Network (NASH CRN), Incidence of type 2 diabetes in children with nonalcoholic fatty liver disease. Clin Gastroenterol Hepatol. Published online June 13, 2022. doi:10.1016/j.cgh.2022.05.028.