Background: NAFLD is strongly associated with type 2 diabetes. Insulin resistance is proposed as a major contributor. NAFLD is increasingly reported in type 1 diabetes (T1D) , but whether insulin resistance is linked to NAFLD in this population needs elucidation. Furthermore, T1D is an excellent model to investigate insulin resistance in relation to NAFLD without confounding by autologous insulin production.

Aims and Methods: We aimed to assess whether insulin resistance is correlated with liver fat content (LFC) in adults with T1D without causes of secondary liver fat accumulation. A hyperinsulinemic-euglycemic clamp (HEC) was performed according to DeFronzo et al. LFC was measured by magnetic resonance spectroscopy (MRS) and calculated as the mean of three independent regions of interest. NAFLD was diagnosed by LFC > 6.0 % and NAFLD subjects were matched 1:1 to no-NAFLD controls based on age and sex.

Results: 20 subjects with an age of 48 ± 17 y, a BMI of 27.3 ± 4.3 kg/m2, and a HbA1c of 7.3 ± 0.8 % were included. Mean M-index (HEC-derived index of insulin sensitivity) was 5.12 ± 3.03 mg/kg/min. Mean LFC was 15.6 ± 8.3 % (NAFLD) versus 2.8 ± 1.4 % (controls) , p < 0.001. Mean M-index differed significantly (2.88 ± 1.58 [NAFLD] vs. 6.74 ± 2.[controls] mg/kg/min, p < 0.001) . BMI was significantly higher in the NAFLD group (29.6 ± 3.6 vs. 25.1 ± 3.8 kg/m2, p = 0.014) . There was a strong correlation between the M-index and LFC (r = -0.85, p < 0.001) . Linear regression showed a significant association between LFC (dependent) and M-index (B = -1.504, 95% CI: (-2.9to -0.101) , p = 0.037) and BMI (B = 0.879, 95% CI: (0.047 to 1.711) , p = 0.040) but not age or HbA1c level as independent variables.

Conclusion: HEC-derived measures of insulin resistance are strongly correlated to LFC in people with T1D, independently from BMI. These data support the pivotal role of insulin resistance in NAFLD pathophysiology and as a target for NAFLD therapy in T1D.


J.Mertens: None. R.Braspenning: None. F.Vanhevel: None. M.Spinhoven: None. S.Francque: None. C.De block: Advisory Panel; Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Medtronic, Novo Nordisk, Research Support; Indigo Diabetes, Speaker’s Bureau; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Novo Nordisk.

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