Characteristics of Islet β-cell Functions in Chinese Patients With Graves' Disease

Study Overview
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Brief Summary
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Patients with GD often present with glucose dysregulation, which, according to most studies, is associated with islet β-cell dysfunctions, enhanced gluconeogenesis and insulin resistance (IR). Current studies focus mainly on IR, and a few that investigate islet β-cell functions show inconsistent results. This study examined the characteristics of glucose dysregulation in Chinese patients with GD, and furthermore evaluated the effects of thyroid dysfunction on islet β-cell functions and subsequently the carbohydrate metabolism.

Detailed Description
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Thyroid dysfunction is closely associated with glucoregulation. Carbohydrate metabolism can be affected with decreased levels of thyroid hormone (TH), even more so with an elevated TH level. Epidemiological data shows that 2%-57% of patients with Graves' Disease (GD) present with glucose dysregulation, which might also be related to the changes in islet β-cell functions in patients with GD. The incidence of GD has comparable variations geographically, with possibly different underlying mechanisms, such as an excessive intake of iodine resulting in an aggravation of autoimmune reactions from thyroid and consequently an increment in incidence of GD. The same might also be true in glucoregulation and islet β-cell functions in patients with GD. This study aims to examine the characteristics of glucoregulation and islet β-cell functions in patients with GD in different areas of China, using early-phase insulin secretion index (△I30/△G30), glucose area under curve(GAUC) and insulin area under curve(INSAUC).

Official Title
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Characteristics of Islet β-cell Functions in Chinese Patients With Graves' Disease

Conditions
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Graves Disease

Intervention / Treatment
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* Drug: Methimazole


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with Graves Disease Age-matched healthy checkup subjects Exclusion Criteria: Patients with a medical history of diabetes, pancreatitis and other related conditions and positive family histories as well as medication history of glucocorticoid and anti-diabetic agents

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| GA1<br>subjects from coastal areas who initiated Methimazole treatment for the first time on enrollment | Drug: Methimazole<br>* All enrolled subjects with GD were treated with methimazole. The initial dose for the GA1 and GB1 sungroups were 30 mg/d (10 mg, tid), TH levels were tested every month, and the dose was titrated accordingly over a period of 2-3 months, the dose was then decreased to 15-20 mg/d and thyroid function was monitored periodically until it eventually reached the maintenance dose of 2.5 mg-5.0 mg/d. The dose and adjustment method for GA2 and GB2 were the same with GA1 and GB1, while the dose for GA3 and GB3 was gradually decreased to 2.5-5.0 mg/d. All subjects underwent a treatment course over a period of 6 months.<br>* Other names: Thyrozol;|
| GA2<br>subjects from coastal areas who were under Methimazole treatment and with an elevated TH level | Drug: Methimazole<br>* All enrolled subjects with GD were treated with methimazole. The initial dose for the GA1 and GB1 sungroups were 30 mg/d (10 mg, tid), TH levels were tested every month, and the dose was titrated accordingly over a period of 2-3 months, the dose was then decreased to 15-20 mg/d and thyroid function was monitored periodically until it eventually reached the maintenance dose of 2.5 mg-5.0 mg/d. The dose and adjustment method for GA2 and GB2 were the same with GA1 and GB1, while the dose for GA3 and GB3 was gradually decreased to 2.5-5.0 mg/d. All subjects underwent a treatment course over a period of 6 months.<br>* Other names: Thyrozol;|
| GA3<br>subjects from coastal areas who were under Methimazole treatment and with a normal TH level | Drug: Methimazole<br>* All enrolled subjects with GD were treated with methimazole. The initial dose for the GA1 and GB1 sungroups were 30 mg/d (10 mg, tid), TH levels were tested every month, and the dose was titrated accordingly over a period of 2-3 months, the dose was then decreased to 15-20 mg/d and thyroid function was monitored periodically until it eventually reached the maintenance dose of 2.5 mg-5.0 mg/d. The dose and adjustment method for GA2 and GB2 were the same with GA1 and GB1, while the dose for GA3 and GB3 was gradually decreased to 2.5-5.0 mg/d. All subjects underwent a treatment course over a period of 6 months.<br>* Other names: Thyrozol;|
| GB1<br>subjects from non-coastal areas who initiated Methimazole treatment for the first time on enrollment | Drug: Methimazole<br>* All enrolled subjects with GD were treated with methimazole. The initial dose for the GA1 and GB1 sungroups were 30 mg/d (10 mg, tid), TH levels were tested every month, and the dose was titrated accordingly over a period of 2-3 months, the dose was then decreased to 15-20 mg/d and thyroid function was monitored periodically until it eventually reached the maintenance dose of 2.5 mg-5.0 mg/d. The dose and adjustment method for GA2 and GB2 were the same with GA1 and GB1, while the dose for GA3 and GB3 was gradually decreased to 2.5-5.0 mg/d. All subjects underwent a treatment course over a period of 6 months.<br>* Other names: Thyrozol;|
| GB2<br>subjects from non-coastal areas who were under Methimazole treatment and with an elevated TH level | Drug: Methimazole<br>* All enrolled subjects with GD were treated with methimazole. The initial dose for the GA1 and GB1 sungroups were 30 mg/d (10 mg, tid), TH levels were tested every month, and the dose was titrated accordingly over a period of 2-3 months, the dose was then decreased to 15-20 mg/d and thyroid function was monitored periodically until it eventually reached the maintenance dose of 2.5 mg-5.0 mg/d. The dose and adjustment method for GA2 and GB2 were the same with GA1 and GB1, while the dose for GA3 and GB3 was gradually decreased to 2.5-5.0 mg/d. All subjects underwent a treatment course over a period of 6 months.<br>* Other names: Thyrozol;|
| GB3<br>subjects from non-coastal areas who were under Methimazole treatment and with a normal TH level | Drug: Methimazole<br>* All enrolled subjects with GD were treated with methimazole. The initial dose for the GA1 and GB1 sungroups were 30 mg/d (10 mg, tid), TH levels were tested every month, and the dose was titrated accordingly over a period of 2-3 months, the dose was then decreased to 15-20 mg/d and thyroid function was monitored periodically until it eventually reached the maintenance dose of 2.5 mg-5.0 mg/d. The dose and adjustment method for GA2 and GB2 were the same with GA1 and GB1, while the dose for GA3 and GB3 was gradually decreased to 2.5-5.0 mg/d. All subjects underwent a treatment course over a period of 6 months.<br>* Other names: Thyrozol;|
| NC<br>age-matched healthy checkup subjects | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change from baseline blood glucose at 6 months |  | at the day of the subject's enrollment into the study(baseline) and at 6 months after the enrollment | 
| change from baseline insulin at 6 months |  | at the day of the subject's enrollment into the study(baseline) and at 6 months after the enrollment | 
| change from baseline thyroid hormone at 6 months |  | at the day of the subject's enrollment into the study(baseline) and at 6 months after the enrollment | 
| change from baseline urine iodine concentration at 6 months |  | at the day of the subject's enrollment into the study(baseline) and at 6 months after the enrollment |