Markers of Early Liver Dysfunction Associate With Reduced Heart Rate Variability in Adolescents With Type 1 Diabetes

Aim: Data on the impact of metabolic dysfunction-associated fatty liver disease (MAFLD) on diabetes complications in youth with type 1 diabetes are lacking. However, MAFLD is well known to contribute to cardiovascular disease (CVD) in people with type 2 diabetes. We aimed to investigate markers of MAFLD in youth with type 1 diabetes and their relationship with chronic complications. Methods: A prospective study of 102 adolescents (mean age 14.7 ± 1.9 years) with type 1 diabetes underwent repeated annual diabetes complications assessments, including annual measures of liver enzymes. Early cardiac autonomic nerve dysfunction (CAN) was defined as ≥1 abnormality in seven heart rate variability parameters derived from a 10-min resting electrocardiogram. Multivariate generalized estimating equations explored predictors of CAN and other microvascular complications (retinopathy and early kidney dysfunction). Results: After a median follow-up of 3.5 years (IQR 2.7-4.6), there were significant increases in the mean alanine transaminase level (ALT) and systolic blood pressure (SBP) percentiles. Upper ALT and gamma-glutamyl transferase (GGT) tertiles (T3 vs. T1-2: odds ratio [OR], 95% confidence interval [CI], 2.05 [1.20, 3.48], and 2.99 [1.61, 5.58], respectively) predicted CAN development (23%, n = 24) independent of HbA1c and diabetes duration. They were not associated with retinopathy or early kidney dysfunction. Conclusion: Higher ALT and GGT associate with early CAN in adolescents with type 1 diabetes, suggesting hepatic inflammation may compound the impact of the diabetes milieu on systemic endothelial dysfunction.