Serum Betatrophin Levels and Its Influencing Factors in Patients With Hyperthyroidism

Hyperthyroidism Clinical Trial

Official title:

Serum Betatrophin Levels and Its Influencing Factors in Patients With Hyperthyroidism

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02812888
• Other study ID #: FirstPHXuzhou
• Secondary ID: ChiCTR
• Status: Recruiting
• Phase: N/A
• First received: June 20, 2016
• Last updated: July 5, 2016
• Start date: July 2016
• Est. completion date: June 2017

Study information

• Verified date: July 2016
• Source: The First People's Hospital of Xuzhou
• Contact: Hu Hao, MD
• Phone: +86 13685135953
• Email: 18361811955[@]163.com
• Is FDA regulated: No
• Health authority: China: Jiangsu Provincial Commission of Health and Family Planning
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Clustering of various metabolic parameters including abdominal obesity, hyperglycaemia, low high-density lipoprotein cholesterol, elevated triglycerides and hypertension have been used worldwide as metabolic syndrome to predict cardiometabolic risk. Thyroid dysfunction impacts on various levels of these components.

Recent evidence from HepG2 cells indicates that betatrophin, also known as TD26/RIFL/lipasin/ANGPTL8/C19orf80, a secreted protein that regulates glucose, lipid metabolism, and energy homeostasis, is induced by T3. However, the role of betatrophin in hyperthyroid patients is unknown.

The objective was to study serum betatrophin levels in hyperthyroid patients and the association of serum betatrophin levels with hyperthyroidism.

Description:

Thyroid hormone (TH) is a critical hormone responsible for growth, development, and metabolism. It maintains basal metabolic rate (BMR), improves adaptive thermogenesis, and thus modulates body weight by fine-tuning energy expenditure and intake. Hyperthyroidism, a condition with excess TH, presents a status of negative energy balance that is characterized by weight loss, increased energy expenditure, and accelerated lipolysis and gluconeogenesis. The mechanism underlying hypermetabolic status in hyperthyroidism is complicated. In hyperthyroidism, excess TH promotes the metabolism rate primarily by binding to TH receptor α or β, and in turn by further influencing diverse metabolic pathways. Recent studies have revealed that TH signals were involved in cross talk with a range of other metabolic signaling pathways in different metabolic organs. In liver, TH interacts with peroxisome proliferator-activated receptor (PPAR) α, PPARγ, and liver X receptor α pathway; promotes fatty acid oxidation; decreases cholesterol; and enhances gluconeogenesis. The elements required for TH action are well documented, but understanding the interaction between TH and various pathways remains a challenge.

Betatrophin, also known as TD26/RIFL/lipasin/ANGPTL8/C19orf80, is a novel protein predominantly expressed in human liver. Increasing evidence has revealed associations between betatrophin expression, glycemia and serum lipid profiles, particularly in patients with obesity or diabetes. Stimulators of betatrophin, such as insulin, thyroid hormone, irisin, SIRT1 and caloric intake, are usually relevant to energy expenditure or thermogenesis. A previous report revealed that betatrophin mRNA is induced by the thyroid hormone in HepG2 cells. Subsequent studies confirmed that transcriptional regulation is dependent on the thyroid hormone receptor that binds to the betatrophin upstream element. Therefore, betatrophin is a novel gene dramatically activated by the thyroid hormone. However, there is no evidence to date showing that TH is capable of regulating betatrophin expression in human beings. The current study investigated the change of betatrophin levels in patients with hyperthyroidism before and after thionamide treatment and explored the association of serum betatrophin levels with hyperthyroidism.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 240
• Est. completion date: June 2017
• Est. primary completion date: March 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

Inclusion Criteria:

• Clinical diagnosis of hyperthyroidism

• Must be drug-naive before recruitment

Exclusion Criteria:

• diabetes

• hypertension

• cancer

• pregnancy

• lactation

• subacute thyroiditis

• postpartum thyroiditis

• abnormal liver function

• abnormal kidney function

• infectious diseases

Study Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Hyperthyroidism

Intervention

Drug:
• thionamide treatment for 3 months
Hyperthyroid patients would received thionamide treatment (methimazole, propylthiouracil, or propranolol) for 3 months, and euthyroidism would be obtained.

Locations

Country	Name	City	State
China	The First People's Hospital of Xuzhou,	Xuzhou	Jiangsu

Sponsors (1)

Lead Sponsor	Collaborator
Hu Hao

Country where clinical trial is conducted

China, 

References & Publications (8)

Dong XY, Pang XW, Yu ST, Su YR, Wang HC, Yin YH, Wang YD, Chen WF. Identification of genes differentially expressed in human hepatocellular carcinoma by a modified suppression subtractive hybridization method. Int J Cancer. 2004 Nov 1;112(2):239-48. — View Citation

Lopez D, Abisambra Socarrás JF, Bedi M, Ness GC. Activation of the hepatic LDL receptor promoter by thyroid hormone. Biochim Biophys Acta. 2007 Sep;1771(9):1216-25. Epub 2007 May 21. — View Citation

Quagliarini F, Wang Y, Kozlitina J, Grishin NV, Hyde R, Boerwinkle E, Valenzuela DM, Murphy AJ, Cohen JC, Hobbs HH. Atypical angiopoietin-like protein that regulates ANGPTL3. Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19751-6. doi: 10.1073/pnas.1217552109. Epub 2012 Nov 12. — View Citation

Ren G, Kim JY, Smas CM. Identification of RIFL, a novel adipocyte-enriched insulin target gene with a role in lipid metabolism. Am J Physiol Endocrinol Metab. 2012 Aug 1;303(3):E334-51. doi: 10.1152/ajpendo.00084.2012. Epub 2012 May 8. — View Citation

Ribeiro MO, Carvalho SD, Schultz JJ, Chiellini G, Scanlan TS, Bianco AC, Brent GA. Thyroid hormone--sympathetic interaction and adaptive thermogenesis are thyroid hormone receptor isoform--specific. J Clin Invest. 2001 Jul;108(1):97-105. — View Citation

Tseng YH, Ke PY, Liao CJ, Wu SM, Chi HC, Tsai CY, Chen CY, Lin YH, Lin KH. Chromosome 19 open reading frame 80 is upregulated by thyroid hormone and modulates autophagy and lipid metabolism. Autophagy. 2014 Jan;10(1):20-31. doi: 10.4161/auto.26126. Epub 2 — View Citation

Yi P, Park JS, Melton DA. Betatrophin: a hormone that controls pancreatic ß cell proliferation. Cell. 2013 May 9;153(4):747-58. doi: 10.1016/j.cell.2013.04.008. Epub 2013 Apr 25. — View Citation

Zhang R. Lipasin, a novel nutritionally-regulated liver-enriched factor that regulates serum triglyceride levels. Biochem Biophys Res Commun. 2012 Aug 10;424(4):786-92. doi: 10.1016/j.bbrc.2012.07.038. Epub 2012 Jul 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum betatrophin levels		Change from baseline at 3 months	No
Secondary	Thyroid function index		At baseline and at the end of the third month	No
Secondary	blood lipid profile		At baseline and at the end of the third month	No
Secondary	liver function index		At baseline and at the end of the third month	No
Secondary	hypersensitive c-reactive protein (hs-CRP)		At baseline and at the end of the third month	No
Secondary	Blood glucose		At baseline and at the end of the third month	No
Secondary	Serum insulin levels		At baseline and at the end of the third month	No

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