Thyroid Hormone Shows Promise For Fighting NAFLD

A thyroid hormone shows promise in fighting non-alcoholic fatty liver disease (NAFLD) in patients with diabetes, according to new research.

The disease, a major global health problem characterized by accumulation of fat in the liver, develops in patients with obesity, type 2 diabetes, dyslipidaemia, and insulin resistance.

The presence of excess fat in the liver can be a long silent process. As the disease progresses, the liver becomes unable to function normally, at which point the damage is non-reversible.

Researchers previously showed that thyroid hormone was important for metabolism of fatty acids in rodent liver and cell culture models. Additionally, they showed that thyroid hormone levels in the liver may be decreased in rats with NAFLD, therefore supplementation with thyroid hormone could be beneficial for patients with NAFLD.

Thyroxine Hormone Therapy

Now, Eveline Bruinstroop and Paul M. Yen from Duke-NUS Medical School and their colleagues have completed a clinical study that shows low-dose thyroid hormone supplementation may be beneficial for reducing fatty liver in male diabetic patients with NAFLD.

In the trials, 20 NAFLD patients with stable type 2 diabetes and normal thyroid function received thyroxine hormone therapy for four months at the particular dosage that researchers tailored to obtain the desirable TH level individually.

Researchers performed magnetic resonance imaging (MRI) scans before and after TH treatment to measure the changes in various fat depots including liver fat content. They also monitored other clinical measurements such as the control of blood glucose levels.

Patients who had a larger decrease in intrahepatic lipid content also showed improvements of their diabetes.

“This is the first clinical study that showed low-dose thyroid hormone decreases both liver fat as well as overall body fat in a safe manner in male type 2 diabetic patients with NAFLD. The decrease in liver fat also correlates with an improvement in diabetes control after treatment. This pilot study provides a strong rationale for further investigation, development, and testing of thyroid hormone or thyroid hormone analogues in diabetic patients with NAFLD,”

says Yen, who is from the Cardiovascular and Metabolic Disorders Program at Duke-NUS Medical School.

Measuring Metabolic Activity

In this study, S. Sendhil Velan from the Agency of Science and Technology Research’s Singapore Bioimaging Consortium and his team implemented non-invasive magnetic resonance imaging and spectroscopic techniques to quantitatively assess visceral fat, subcutaneous fat, and liver fat before and after TH treatment in NAFLD patients. SBIC plans to conduct more studies to evaluate the changes in fat composition within liver fat in response to an intervention.

“Through leveraging our collective expertise and capabilities, we gained valuable insights into the relationship between the thyroid hormone and the metabolism of fatty acids in functional organs. The successful clinical study affirms magnetic resonance imaging and spectroscopic approaches as gold standards for measuring metabolic activity, and these will support future clinical studies in non-alcoholic fatty liver disease, and the development of medical treatments that improve health outcomes,”

says Velan.

Tanoto Initiative for Diabetes Research funded the research. The research trial was conducted through the Metabolic Research Network of SCRI, and involved six clinical centers across Singapore: Tan Tock Seng Hospital, Singapore General Hospital, Ng Teng Feng General Hospital, Changi General Hospital, Khoo Teck Puat Hospital, and National University Hospital.

Eveline Bruinstroop, Rinkoo Dalan, Yang Cao, Yong Mong Bee, Kurumbian Chandran, Li Wei Cho, Shui Boon Soh, Eng Kiong Teo, Sue-Anne Toh, Melvin Khee Shing Leow, Rohit A Sinha, Suresh Anand Sadananthan, Navin Michael, Heather M Stapleton, Christopher Leung, Peter W Angus, Sheila K Patel, Louise M Burrell, Su Chi Lim, Chee Fang Sum, S Sendhil Velan, Paul M Yen
Low-Dose Levothyroxine Reduces Intrahepatic Lipid Content in Patients With Type 2 Diabetes Mellitus and NAFLD
The Journal of Clinical Endocrinology & Metabolism, Volume 103, Issue 7, 1 July 2018, Pages 2698–2706, https://doi.org/10.1210/jc.2018-00475

Image: Marco Verch/Flickr