Uncontrolled Type 1 Diabetes Linked With MASLD Risk in Pediatric Patients

Children with uncontrolled type 1 diabetes (T1D) appear to face an increased risk of developing metabolic dysfunction–associated steatotic liver disease (MASLD), a new study has found.¹

This report, published in Journal of Pediatric Gastroenterology and Nutrition, suggests better screening of children with T1D might help prevent liver problems later in life.

The study authors say previous research has clearly identified an association between type 2 diabetes and MASLD.

“However, the link between MASLD and type 1 diabetes has been less well explored,” they wrote. “Some studies in children with T1D have reported varying MASLD prevalence (0%-27%).”

For this analysis, alanine aminotransferase values were considered elevated if they exceeded 26 U/L in males or 22 U/L in females | Image Credit: Ana - stock.adobe.com

Given what is already known about the disease, the authors said it is important to better understand whether children with T1D are at greater risk of MASLD.

“Early onset MASLD, often detected as elevated alanine aminotransferase (ALT) levels in pediatric patients, is a potentially reversible condition,” they wrote. “Nevertheless, MASLD is the leading cause of liver fibrosis to date.” Being able to better identify early signs of MASLD in children and adolescents would create the opportunity for early therapeutic intervention, they said.

To study the question, they used a database of children with T1D in Germany, Austria, and Switzerland, ultimately including 32,325 children aged 2 to 17 years who had undergone at least 1 assessment of liver enzyme levels. They then used multivariable logistic and Cox regression models to assess potential links between elevated ALT values and T1D, the former serving as a proxy for MASLD. For the purposes of this study, ALT values were considered elevated if they exceeded 26 U/L in males or 22 U/L in females. Poorly controlled T1D was defined as having hemoglobin A1C levels in excess of 11%.

After adjusting for age, sex, duration of diabetes, and overweight status, the investigators found that children with poorly controlled T1D had a significantly heightened risk for elevated ALT values (OR, 2.54; 95% CI, 2.10-3.10; P < .01). The authors also performed a longitudinal analysis, which found that uncontrolled T1D was linked with a risk of elevated ALT values compared with children with controlled T1D over an observation period of up to 5.5 years (HR, 1.54; 95% CI, 1.19-2.01; P < .01).

The authors said these data help illustrate the high stakes for children with uncontrolled T1D.

“Recent studies have shown that 15% of children with MASLD develop cirrhosis, with 3% progressing to liver failure and requiring liver transplantation,” they wrote.

Yet, they added that there are many questions remaining related to elevated transaminase levels in children with T1D. They noted that one study found that effective glycemic control can quickly improve transaminase and hepatomegaly,² although the benefit of glycemic control is less pronounced in patients with obesity and concomitant metabolic syndrome.

“The authors claim that this effect may be due to glycogen accumulation in patients with poorly controlled diabetes, raising the question of whether and to what degree elevated transaminase levels in patients in the present study might be attributed to glycogen accumulation,” they wrote.

The investigators noted that currently neither American nor European practice guidelines call for screening patients with T1D for MASLD. They said such screening could not only help improve early detection of MASLD, but add to the available scientific data.

“Our findings further emphasize the importance of considering T1D and its association with overweight and [metabolic syndrome] as a risk factor for MASLD development and the potential benefits of targeted screening and prevention strategies in this high-risk population,” they wrote.

References

1. Koutny F, Wiemann D, Eckert A, et al. Poorly controlled pediatric type 1 diabetes mellitus is a risk factor for metabolic dysfunction associated steatotic liver disease (MASLD): An observational study. J Pediatr Gastroenterol Nutr. Published online April 1, 2024. doi:10.1002/jpn3.12194
2. El-Sayed MH, Thabet RA, Hamza MT, Hussein MS, El Saeed MM. Liver disease in children and adolescents with type 1 diabetes mellitus: a link between glycemic control and hepatopathy. Diabetes Res Clin Pract. 2020:108458. doi:10.1016/j.diabres.2020.108458