High liver fat associated with impaired glucose, type 2 diabetes in pediatric obesity
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Children with obesity and a high level of liver fat content are more likely to have impaired glucose tolerance, prediabetes and type 2 diabetes compared with those with normal liver fat content, according to a speaker
Sonia Caprio, MD, professor of pediatric endocrinology at the Yale University School of Medicine, said nonalcoholic fatty liver disease (NAFLD) is also associated with alterations in glucose and lipid metabolism for children with obesity and may be an early predictor of type 2 diabetes. Caprio discussed the relationship between NAFLD and diabetes at the World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease.
“NAFLD has become one of the most common chronic liver diseases in obese children and adolescents,” Caprio told Healio. “While in adults a strong relationship exists between NAFLD and diabetes, little is known in pediatrics. Understanding of the various pathophysiological mechanisms involved is essential not only for early diagnosis and management, but also for prevention of severe disease forms. Despite the tremendous progress made in recent times in acquiring knowledge about these highly prevalent diseases, the guidelines and recommendations for screening and management of diabetics with NAFLD remain vague, particularly for kids.”
High liver fat linked to impaired glucose
Data from a study published in JAMA Pediatrics revealed NAFLD may be a predictor for type 2 diabetes and CVD. In a large multicenter cohort of children with biopsy-proven NAFLD, 30% of children had prediabetes and 6.5% had type 2 diabetes. Children with prediabetes (OR = 1.9; 95% CI, 1.21-2.9) or type 2 diabetes (OR = 3.1; 95% CI, 1.5-6.2) were more likely to have nonalcoholic steatohepatitis (NASH) compared with those with normal glucose.
Another study published in Hepatology analyzed whether there was a relationship between glucose dysregulation and liver fat content in 118 adolescents with obesity and similar degrees of overall adiposity. Participants were stratified into tertiles by liver fat content. There were no differences in BMI and total fat in the three tertiles; however, those with high liver fat had a higher hepatic fat fraction compared with children with low or moderate liver fat content. A higher prevalence of IGT, type 2 diabetes and metabolic syndrome was observed in those with high liver fat content compared with normal liver fat content.
Similar findings were observed in an analysis of 800 children in the Yale Pediatric NAFLD Cohort. Participants were stratified into tertiles by protein density fat fraction percentage and alanine aminotransferase (ALT). Those in the highest tertile for both protein density fat fraction and ALT had higher fasting glucose and 2-hour glucose than those in the two lower tertiles.
“There is this coexistence of these two phenotypes among some of these kids, which is quite concerning,” Caprio said during the presentation.
Intrahepatic fat and insulin resistance
Intrahepatic fat is also an independent contributor to the development of insulin resistance. In a study published in Diabetes Care in 2010, 61 adolescents with obesity were stratified into a high liver fat content group (n = 23) and a low liver fat content group (n = 38) based on hepatic fat fraction percentage. The high liver fat group had higher triglycerides, ALT, fasting insulin, fasting C-peptide and adiponectin compared with the lower liver fat cohort. Among participants receiving a low-dose insulin infusion, those with high liver fat content had lower suppression of lipolysis and lower suppression of hepatic glucose production. In those receiving a high-dose insulin infusion, peripheral glucose disposal rate was lower for children with high liver fat compared with low liver fat.
Caprio said researchers are planning to conduct a study to examine the efficacy of GLP-1 analogues for the treatment of early youth-onset type 2 diabetes and NAFLD in children with obesity. The study will be funded by the National Institute of Diabetes and Digestive and Kidney Diseases.
“[Prediabetes and NAFLD] seem to be highly connected,” Caprio told Healio. “Treatment using a GLP-1 analogue could improve them and stop the progression of both diseases toward more advanced stages.”
References:
- Cali AM, et al. Hepatology. 2009;doi:10.1002/hep.22858.
- D’Adamo E, et al. Diabetes Care. 2010;doi:10.2337/dc10-0284.
- Newton KP, et al. JAMA Pediatr. 2016;doi:10.1001/jamapediatrics.2016.1971.
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Caprio S. Coexistence of prediabetes and nonalcoholic fatty liver disease in pediatric obesity. Presented at: World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease; Dec. 2-4, 2021; Los Angeles (hybrid meeting).
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