Elevated liver fat content is independently associated with insulin resistance in people with type 1 diabetes

Insulin resistance is associated with metabolic dysfunction-associated steatotic liver disease (MASLD) in the general population, but its relationship with MASLD in individuals with type 1 diabetes (T1D) remains insufficiently defined.

We performed a 40 mU/m²/min hyperinsulinaemic-euglycaemic clamp to quantify the whole-body glucose disposal rate (M-value, mg/kg/min). Furthermore, we assessed insulin sensitivity using ¹³C-glucose breath test and estimated glucose disposal rate. Liver fat content (LFC) was measured by magnetic resonance spectroscopy. We also performed vibration-controlled transient elastography. Participants were stratified 1:1 by MASLD status based on mean LFC >/≤5.56%.

We studied 39 adults with T1D (diabetes duration 27 ± 13 years; haemoglobin A1c 6.9 [6.5-7.8]%). Mean M-value was 4.41 ± 2.37 mg/kg/min. LFC was higher in individuals with MASLD than in those without MASLD (8.2 [6.5-18.7]% vs 3.0 [2.3-3.6]%, p <0.001). The M-value was significantly lower in the MASLD group (2.92 ± 1.39 vs 6.41 ± 2.46 mg/kg/min, p <0.001). LFC strongly correlated with the M-value (r_s -0.72, p <0.001). In linear regression, the M-value independently predicted log-transformed LFC (B -0.22, p <0.001; R² = 0.47). Lower M-value was associated with MASLD (adjusted odds ratio [aOR] 3.12, 95% CI 1.17-8.37, p = 0.024). Both ¹³C-glucose breath test (aOR 1.54, 95% CI 1.03-2.33, p = 0.033) and estimated glucose disposal rate (aOR 1.61, 95% CI 1.09-2.38, p = 0.016) were also independently associated with MASLD.

Insulin resistance is independently associated with MASLD in adults with T1D.

This study addresses the limited understanding of how MASLD relates to insulin resistance in T1D. We show a robust association between LFC and insulin resistance using gold standard and practical non-invasive measures. These findings may help clinicians identify metabolically at-risk individuals with T1D; however, further research is warranted to clarify whether screening and targeted intervention improve outcomes.