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

BACKGROUND & AIMS: 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.

METHODS

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%.

RESULTS

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 (rs -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.

CONCLUSIONS

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

IMPACT AND IMPLICATIONS: 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.