Beta-cell, but not autonomic nervous system, function is related to MAFLD in early stages of glucose intolerance

Previous studies have suggested an association between beta-cell and autonomic function and metabolic-associated fatty liver disease (MAFLD). We explored the association between controlled attenuated parameter (CAP) and insulin secretion and action, as well as sympathetic and parasympathetic activity in normal (NGT) and impaired (IGT) glucose tolerance.

Twenty-five NGT (age 44.8±9.6 years; body mass index (BMI) 32.3±6.9 kg/m²) and 27 IGT (47.6±11.8 years; 31.0±6.5 kg/m²) subjects underwent a 75 g oral glucose tolerance test (OGTT) and a mixed meal tolerance test (MMTT) for assessment of glucose and insulin secretion. Parameters of beta-cell function and insulin sensitivity were calculated. Body composition was assessed by bioimpedance analysis (Inbody720). Autonomic function was assessed by ANX V.3.0 monitoring system. CAP was determined by Fibroscan (Echosense) and presence of MAFLD was defined as CAP >233 dB/m.

A CAP >233 dB/m was found in 72% of subjects with NGT and 67% of subjects with IGT. Subjects with MAFLD, irrespective of glucose tolerance, had higher BMI and waist circumference, lower insulin secretion and action, and lower parasympathetic activity. On a matrix analysis, after adjustment for age and BMI, CAP was positively related to systolic blood pressure (SBP); insulin action was negatively related to parasympathetic activity. Regression analysis showed that AUC-insulin MMTT remained independently related to MAFLD: OR 24.4 (95% CI 2.17 to 274.77; p=0.010). A "cut-off" value of 15,620 uIU/mL^-1*180 min^-1 provided a 75% sensitivity and 75% specificity for CAP >233 dB/m.

Our results do not support a role for parasympathetic activity in MAFLD. Rather, they show that stimulated hyperinsulinemia may be associated with greater risk of MAFLD irrespective of glucose tolerance in a high-risk population without diabetes.