Clinical trial NCT02812888: Serum Betatrophin Levels and Its Influencing Factors in Patients With Hyperthyroidism
Official title: Serum Betatrophin Levels and Its Influencing Factors in Patients With Hyperthyroidism
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Hyperthyroidism
Keywords: Hyperthyroidism
Betatrophin
Lead sponsor: The First People's Hospital of Xuzhou
Sponsor class: OTHER
First posted: 2016-06-24
Enrollment: 240
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with hyperthyroidism would be recruited from the Department of Endocrinology, the First People's Hospital of Xuzhou, from May, 2016, to May, 2017. During the same period, the healthy controls would be selected.

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Serum betatrophin levels
timeFrame: Change from baseline at 3 months
Secondary outcomes:
measure: Thyroid function index
timeFrame: At baseline and at the end of the third month
measure: blood lipid profile
timeFrame: At baseline and at the end of the third month
measure: liver function index
timeFrame: At baseline and at the end of the third month
measure: hypersensitive c-reactive protein (hs-CRP)
timeFrame: At baseline and at the end of the third month
measure: Blood glucose
timeFrame: At baseline and at the end of the third month
measure: Serum insulin levels
timeFrame: At baseline and at the end of the third month
Other outcomes:
Locations:
city: Xuzhou
country: China
facility: The First People's Hospital of Xuzhou,
state: Jiangsu
Study officials:
affiliation: The First People's Hospital of Xuzhou
name: Wang Zhaoling, BD
role: STUDY_CHAIR
affiliation: The First People's Hospital of Xuzhou
name: Hu Hao, MD
role: STUDY_DIRECTOR
affiliation: The First People's Hospital of Xuzhou
name: Gao Zhaohua, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First People's Hospital of Xuzhou
name: Zhou Tingting, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First People's Hospital of Xuzhou
name: Yin Wenwen, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: The First People's Hospital of Xuzhou
name: Cai Ruonan, MD
role: PRINCIPAL_INVESTIGATOR
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