Poorly Controlled Type 1 Diabetes Associated with MASLD in Children, Adolescents

Florian Koutny, MD

Credit: ResearchGate

Findings from a recent study are providing novel insight into the association between metabolic dysfunction associated steatotic liver disease (MASLD) and poorly controlled type 1 diabetes (T1D) in children and adolescents, underscoring the need for effective diabetes management to mitigate the risk of liver injury in this patient population.¹

Results published in the Journal of Pediatric Gastroenterology and Nutrition showed poorly controlled hemoglobin A1C (HbA1C) increased the risk of elevated alanine aminotransferase (ALT) levels, used as a proxy for MASLD, with additional longitudinal analysis revealing this excess risk extended for up to 5.5 years.¹

“Recent research has extensively described the connection between metabolic dysfunction associated steatotic liver disease and type 2 diabetes,” Florian Koutny, MD, of the department of internal medicine at Karl Landsteiner University of Health Sciences in Austria, and colleagues wrote.¹ “However, the link between MASLD and type 1 diabetes has been less well explored.”

According to the US Centers for Disease Control and Prevention, in 2021, 352,000 children and adolescents younger than 20 years of age had diabetes, including 304,000 with T1D.² Liver disease, most commonly MASLD, affects up to 70% of people with type 2 diabetes (T2D). Although the connection between MASLD and T2D is well-established, its association with T1D is less explored.³

To investigate the potential association between poorly controlled T1D and elevated ALT in children and adolescents, investigators analyzed clinical and laboratory data from patients 2-17 years of age with T1D who had received ≥ 1 assessment of liver enzyme levels during routine clinical care in 332 centers across Germany, Austria, Switzerland, and Luxembourg. Anonymized data were gathered from the Diabetes Patient Follow-up Registry, a diabetes-specific electronic health record.¹

For inclusion, patients were required to have a documented diagnosis of T1D and ≥ 1 ALT, HbA1c, and body mass index (BMI) assessment at baseline. Of note, ALT values were used as a surrogate marker for MASLD. For male participants, ALT levels > 26 U/L were considered elevated. For female participants, ALT levels > 22 U/L were considered elevated. Investigators also stratified patients into 3 groups based on their HbA1c levels: Group 1 included those with HbA1c <9%; Group 2 ≥9% to <11%; and Group 3 ≥11%.¹

In total, the study included 32,325 children and adolescents with T1D, including 4645 (14.4%) who presented with elevated ALT at baseline. Investigators pointed out significant differences between the groups for age, BMI, metabolic syndrome, and ALT values.¹

Elevated ALT values at baseline were more common in participants classified as being overweight (odds ratio [OR], 1.58; 95% CI, 1.47−1.70; P <.01), defined as a BMI ≥ 90th percentile (BMI-SDS ≥ 1.28) of the reference population. Additionally, children with HbA1c levels ≥ 11% had 2.54 greater odds of elevated ALT levels compared to children with an HbA1c level < 9% after adjustment for age, sex, diabetes duration, and overweight status (OR, 2.54; 95% CI, 2.10−3.10; P <.01). Further analysis revealed children with HbA1c levels ≥ 11% with additional overweight showed greater odds of elevated ALT values (OR, 2.58; 95% CI, 1.53–4.35; P <.01).¹

Investigators additionally conducted a longitudinal analysis using data from 10,278 participants who had ≥ 1 ALT, HbA1c, and BMI-SDS measurement performed at baseline, 1.5−3.5 years after baseline, and >3.5−5.5 years after baseline. Of note, patients > 25 years of age during follow-up were excluded.¹

Results of this analysis showed inadequately controlled T1D was associated with a greater risk of elevated ALT values compared to children with controlled T1D over an observation period extending up to 5.5 years (Hazard ratio [HR], 1.54; 95% CI, 1.19–2.01; P <.01). Children with HbA1c ≥ 11% and additional overweight status had a 2.71 greater HR of elevated ALT values compared to children with an HbA1c < 9% and without overweight (HR, 2.71; 95% CI, 1.54–4.78; P <.01). However, participants with HbA1c levels between 9% and 11% did not exhibit a significantly increased risk of abnormal ALT values over time, regardless of additional overweight.¹

“Our findings emphasize the importance of regular transaminase monitoring as a fundamental strategy for early detection and prevention of liver injury in pediatric patients with T1D. Insights of the current study contribute to a better understanding of the complex interplay between glycemic control, weight status, and liver health in the context of T1D in children and adolescents,” investigators concluded.¹

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. Journal of Pediatric Gastroenterology and Nutrition. https://doi.org/10.1002/jpn3.12194}
2. ^{US Centers for Disease Control and Prevention. National Diabetes Statistics Report. Diabetes. November 29, 2023. Accessed April 11, 2024. https://www.cdc.gov/diabetes/data/statistics-report/index.html}
3. ^{American Diabetes Association. American Diabetes Association Releases a Guideline Update in NAFLD (Non-Alcoholic Fatty Liver Disease) and Diabetes. Press Release. June 25, 2023. Accessed April 11, 2024. https://diabetes.org/newsroom/american-diabetes-association-releases-guideline-update-NAFLD-diabetes}