Hepatic steatosis is associated with postprandial dysglycemia in type 1 diabetes: insights from dual-modality liver assessment

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is increasingly recognized in type 1 diabetes (T1D), yet its relationship with dynamic glycemic abnormalities and the metabolic pathways underlying these associations remains incompletely understood. We investigated the associations of hepatic steatosis with conventional and continuous glucose monitoring (CGM)-derived glycemic measures in T1D and explored the potential roles of circulating insulin-like growth factor-1 (IGF-1) and insulin resistance. This cross-sectional study included 231 individuals with T1D who underwent hepatic steatosis assessment using ultrasonography and controlled attenuation parameter (CAP). Glycemic status was characterized using glycated hemoglobin (HbA1c), fasting plasma glucose, 1,5-anhydroglucitol (1,5-AG), and, in 142 participants, at least 72 h of valid CGM under standardized inpatient conditions. Multivariable linear regression, false discovery rate correction, and exploratory serial mediation analyses were performed. Ultrasound-defined MASLD was present in 50 participants (21.6%). After multivariable adjustment, ultrasound-defined MASLD and greater CAP were consistently associated with lower 1,5-AG concentrations and less favorable CGM profiles, including higher 2-hour postprandial glucose, glucose peak, mean glucose, glucose management indicator, and time above range, together with lower time in range, whereas fasting glucose was not significantly associated with hepatic steatosis. Hepatic steatosis was also associated with lower circulating IGF-1 concentrations and greater insulin resistance across multiple surrogate indices. In exploratory serial mediation analysis using TG/HDL-C as the primary insulin resistance measure, the combined indirect association through IGF-1 and insulin resistance accounted for 82.6% of the association between MASLD and lower 1,5-AG concentrations, with consistent patterns observed using alternative insulin resistance indices. Hepatic steatosis in T1D is independently associated with a distinct dysglycemic phenotype characterized particularly by short-term and postprandial hyperglycemia. Concurrent differences in circulating IGF-1 and insulin sensitivity may statistically account for a substantial proportion of this association. These findings support hepatic steatosis as a clinically relevant metabolic comorbidity in T1D and warrant prospective studies to clarify the underlying temporal and biological relationships.