Low-Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients With Type 2 Diabetes Mellitus and NAFLD - PubMed (original) (raw)

Clinical Trial

. 2018 Jul 1;103(7):2698-2706.

doi: 10.1210/jc.2018-00475.

Rinkoo Dalan 3 4, Yang Cao 5, Yong Mong Bee 6, Kurumbian Chandran 7, Li Wei Cho 8, Shui Boon Soh 8, Eng Kiong Teo 9, Sue-Anne Toh 10, Melvin Khee Shing Leow 1 3 11, Rohit A Sinha 1, Suresh Anand Sadananthan 11, Navin Michael 11, Heather M Stapleton 12, Christopher Leung 13 14 15, Peter W Angus 13 14, Sheila K Patel 13, Louise M Burrell 13 15, Su Chi Lim 16 17, Chee Fang Sum 16 18, S Sendhil Velan 11 19, Paul M Yen 1

Affiliations

Clinical Trial

Low-Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients With Type 2 Diabetes Mellitus and NAFLD

Eveline Bruinstroop et al. J Clin Endocrinol Metab. 2018.

Abstract

Context: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM) 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.

Objective: We investigated the possibility of low intrahepatic TH concentration in NAFLD and studied the effect of TH treatment in humans.

Design/setting: This was a phase 2b single-arm study in six hospitals in Singapore. Intrahepatic thyroid hormone concentrations were measured in rats with induced NAFLD.

Patients: Euthyroid patients with T2DM and steatosis measured by ultrasonography.

Intervention: Levothyroxine was titrated to reach a thyroid-stimulating hormone level of 0.34 to 1.70 mIU/L before a 16-week maintenance phase.

Main outcome measures: The primary outcome measure was change in IHLC measured by proton magnetic resonance spectroscopy after treatment.

Results: Twenty male patients were included in the per-protocol analysis [mean ± SD: age, 47.8 ± 7.8 years; body mass index (BMI), 30.9 ± 4.4 kg/m2; baseline IHLC, 13% ± 4%]. After treatment, IHLC was decreased 12% (±SEM, 26%) relative to baseline (absolute change, -2%; 95% CI, -3 to 0; P = 0.046). Small decreases in BMI (P = 0.044), visceral adipose tissue volume (P = 0.047), and subcutaneous adipose tissue volume (P = 0.045) were observed. No significant changes in glucose regulation or lipid profile occurred.

Conclusion: This study demonstrated the efficacy and safety of low-dose TH therapy for NAFLD in men. TH or TH analogs may be beneficial for this condition.

Trial registration: ClinicalTrials.gov NCT03281083.

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