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

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.

Study Overview

• Status: Completed
• Conditions: Graves Disease
• Intervention / Treatment: Drug: Methimazole

Detailed Description

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).

• Study Type: Observational
• Enrollment (Actual): 328

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

A total of 283 outpatients, aged 22 to 55 years old(mean age 39±4 years), of whom 41 were male and 242 were female (M/F=1/5.90), were enrolled for the study from Qilu Hospital of Shandong University and Shandong Jiaotong Hospital between June, 2011 and June, 2014. An additional 45 age-matched healthy checkup subjects were included in the normal control group (NC). 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 were excluded.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

7

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
GA1; subjects from coastal areas who initiated Methimazole treatment for the first time on enrollment	Drug: Methimazole; 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.; Other Names: Thyrozol
GA2; subjects from coastal areas who were under Methimazole treatment and with an elevated TH level	Drug: Methimazole; 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.; Other Names: Thyrozol
GA3; subjects from coastal areas who were under Methimazole treatment and with a normal TH level	Drug: Methimazole; 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.; Other Names: Thyrozol
GB1; subjects from non-coastal areas who initiated Methimazole treatment for the first time on enrollment	Drug: Methimazole; 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.; Other Names: Thyrozol
GB2; subjects from non-coastal areas who were under Methimazole treatment and with an elevated TH level	Drug: Methimazole; 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.; Other Names: Thyrozol
GB3; subjects from non-coastal areas who were under Methimazole treatment and with a normal TH level	Drug: Methimazole; 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.; Other Names: Thyrozol
NC; age-matched healthy checkup subjects

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Weikai Hou

Study record dates

Study Major Dates

• Study Start: June 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: February 18, 2015
• First Submitted That Met QC Criteria: February 24, 2015
• First Posted (Estimate): March 3, 2015

Study Record Updates

• Last Update Posted (Estimate): March 3, 2015
• Last Update Submitted That Met QC Criteria: February 24, 2015
• Last Verified: February 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Eye Diseases; Endocrine System Diseases; Thyroid Diseases; Exophthalmos; Orbital Diseases; Goiter; Hyperthyroidism; Graves Disease; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Antithyroid Agents; Methimazole
• Other Study ID Numbers: GD-003