Abstract Context/Objective Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus and associated with significant morbidity and mortality. Thyroid hormone (TH) increases β-oxidation of fatty acids and decreases intrahepatic lipid content (IHLC) in rodents with NAFLD. In this study we investigated the possibility of low intrahepatic TH concentration in NAFLD and studied the effect of TH treatment in humans. Design/Setting We performed a phase 2b single arm study in six hospitals in Singapore to study whether TH reduced IHLC. Rats fed a MCD diet to induce NAFLD were used to show intrahepatic thyroid hormone concentrations. Patients Euthyroid patients with type 2 diabetes mellitus and steatosis measured by ultrasonograpy. Intervention Levothyroxine was titrated at TSH 0.34-1.70 mIU/L before a 16-week maintenance phase. Main outcome measures The primary outcome measure was change in IHLC measured by 1H-MRS after treatment. Results 20 male patients were included in the per protocol analysis (mean age 47.8±7.8 years, BMI 30.9±4.4 kg/m2, baseline IHLC 13±4 %). After treatment IHLC was decreased by 12 % ± 26 % relative to baseline (absolute change -2 %; 95% CI -3 to 0, p=0.046). Small decreases in BMI (p=0.044), VAT volume (p=0.047), and SAT volume (p=0.045) were observed. No significant changes in glucose regulation or lipid profile occurred. Conclusions This is the first study demonstrating the efficacy and safety of low dose TH therapy for NAFLD in man, and suggests that TH or TH analogs may be beneficial for this condition. Copyright © 2018 Endocrine Society
Journal of Clinical Endocrinology and Metabolism – Oxford University Press
Published: Apr 27, 2018
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