Value of Glycated Albumin in Intervention of Glycemic Control in Chinese Patients With Type 2 Diabetes

Study Overview
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Brief Summary
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HbA1c is widely used as the gold standard for evaluating glycemic control. However, in patients who need adjusting hypoglycemic regimen, A1c was not a sensitive marker. In comparison, serum GA level can reflect the average blood glucose level in the last 2 3 weeks of diabetes. Therefore, investigators undertake this study to determine whether knowledge of GA values and adjusting anti-diabetic regimens according to GA values will result in improved glycemic control in newly diagnosed type 2 diabetes mellitus (T2DM). This multicenter randomized controlled clinical study will be conducted in 10 hospitals in China. A total of 200 patients with newly diagnosed T2DM will be 1:1 randomly assigned to two groups: intervention group (GA) and control group (NC). In GA group, the anti-diabetic treatment regimen will be strengthened when GA value is higher than 16% at 4 weeks. In NC group, investigators will be not aware of the GA value and rely on the current guidelines to adjust treatment. At 12-week of follow-up，investigators compare the achievement rate of HbA1c(≤7%) between the two groups.

Detailed Description
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At present, glycosylated hemoglobin (HbA1c) is widely used as the gold standard for evaluating glycemic control. However, as a marker of average blood glucose level, HbA1c has some limitations. HbA1c is affected by many conditions, such as hemolytic anemia, recent blood loss or blood transfusion, chronic renal failure, the use of erythropoietin or other drugs affecting hematopoiesis, and the presence of variant hemoglobin. In addition, HbA1c represents the average blood glucose level in the last 2-3 months, in patients who need adjusting hypoglycemic regimen, A1c was not a sensitive marker. Therefore, finding clinical markers that can timely guide the adjustment and evaluate therapeutic effects is an urgent demand for individualized treatment of diabetes. Glycated albumin (GA) has been available in clinic for sixteen years, yet the clinical value of routine measurements of GA in the care of diabetic patients is still uncertain. Previous studies have shown that the GA half-life is 17-19 days, so the serum GA level can reflect the average blood glucose level and the recent blood glucose changes and the extent of the changes in the last 2 3 weeks of diabetes, and is not affected by age, gender, diet, drugs and glycemic fluctuation. A recent short-term study found that in newly diagnosed type 2 diabetic patients with initial therapy and in patients with type 2 diabetes and unsatisfactory glucose control and need intensifying treatment, changes in GA could predict changes in HbA1c levels after 3 months. Therefore, investigators undertake this study to determine whether knowledge of GA values and adjusting anti-diabetic regimens according to GA values will result in improved glycemic control in newly diagnosed type 2 diabetes mellitus (T2DM). This multicenter randomized controlled clinical study will be conducted in 10 hospitals in China. A total of 200 patients with newly diagnosed T2DM will be 1:1 randomly assigned to two groups: intervention group (GA) and control group (NC). In this study, the clinical related indexes such as GA, fasting blood glucose, HbA1c, fasting C-peptide, fasting insulin, liver and kidney function, blood routine, blood uric acid and blood lipid were measured at baseline. The GA serum was frozen and not used as the basis for initial treatment. All the patients will be treated with antidiabetic therapy according to guideline for prevention and treatment of type 2 diabetes in China (2020) and followed up for 12 weeks. The GA concentration will be measured at 4-week intervals. In GA group, the anti-diabetic treatment regimen will be strengthened when GA value is higher than 16% at 4 weeks. In NC group, investigators will be not aware of the GA value and rely on the current guidelines to adjust treatment. At the end of 12 weeks, A1c and other metabolic indexes will be measured again. All the anti-diabetic drugs are permitted in this study except sulfonylureas, glinides, insulin and insulin analogues.

Official Title
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Value of Glycated Albumin in Intervention of Glycemic Control in Patients With Type 2 Diabetes: A Multicenter, Randomized Controlled Clinical Study

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Other: GA guided anti-diabetic therapy adjustment
* Other: current guidelines to adjust treatment


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 20-70 years of age newly diagnosed T2DM or duration of T2DM less than 1 year and without anti-diabetic medications for 3 months prior to screening HbA1c ≥7.5% and <10.5% Exclusion Criteria: Requiring treatment of proliferative retinopathy, maculopathy, painful diabetic neuropathy, diabetic foot, diabetic ketoacidosis, or hyperglycemic hyperosmolar status in recent 3 months prior to screening. The following history or conditions in recent 6 months prior to screening: (i) decompensated cardiac insufficiency (NYHA class III or IV); (ii)myocardial infarction, coronary artery bypass grafting or coronary stent implantation; (iii) uncontrolled severe arrhythmia and is not suitable to participate in this study evaluated by the investigator; (iv) hemorrhagic stroke or ischemic stroke and is not suitable to participate in this study evaluated by the investigator. Laboratory indicators meet one of the following criteria: (i) alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 3× upper limit of normal(ULN); (ii) total bilirubin > 2× ULN; (iii) hemoglobin <100g/L; (iv)total protein <60g/L; (v)albumin <30g/L; (vi) glomerular filtration rate(eGFR)<60 ml min-1 per 1.73 m2. Thalassemia, hemolytic anemia and other diseases that may cause erythrocyte instability and affect the measurement of HbA1c. Uncontrolled thyroid dysfunction. Systemic corticosteroids treatment in recent 1 month prior to screening (exception of inhalation or local external treatment). Pregnancy or lactating. Two or more episodes of severe hypoglycemia in recent 1 year prior to screening. Patient who need to initiate treatment with sulfonylureas, glinides, insulin or insulin analogues evaluated by the investigators. Patient is being treated with calcium dobesilate or has a disease requiring calcium dobesilate treatment, or may be treated with calcium dobesilate in the near future evaluated by the investigators. Patients considered unsuitable for observation by investigators.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A total of 200 patients with newly diagnosed T2DM will be 1:1 randomly assigned to two groups: intervention group (GA) and control group (NC). After testing baseline metabolic indexes including A1c, all the patients will be treated with antidiabetic therapy according to guideline for prevention and treatment of type 2 diabetes in China (2020) and followed up for 12 weeks. The GA concentration will be measured at 4-week intervals. In GA group, the anti-diabetic treatment regimen will be strengthened when GA value is higher than 16% at 4 weeks. In NC group, investigators will be not aware of the GA value and rely on the current guidelines to adjust treatment. At the end of 12 weeks, A1c and other metabolic indexes will be measured again. All the anti-diabetic drugs are permitted in this study except sulfonylureas, glinides, insulin and insulin analogues.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: GA guided anti-diabetic therapy adjustment<br>The GA concentration will be measured at 4-week intervals and the anti-diabetic treatment regimen will be strengthened when GA value is higher than 16% at 4 weeks. | Other: GA guided anti-diabetic therapy adjustment<br>* The GA concentration will be measured at 4-week intervals in both groups. The anti-diabetic treatment regimen will be strengthened when GA value is higher than 16% at 4 weeks.<br>|
| Active Comparator: current guidelines to adjust treatment<br>The GA concentration will be measured at 4-week intervals，but investigators will be not aware of the GA value and rely on the current guidelines to adjust treatment. | Other: current guidelines to adjust treatment<br>* The GA concentration will be measured at 4-week intervals. Investigators will be not aware of the GA value and rely on the current guidelines to adjust treatment.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The achievement rate of HbA1c (≤7%) | To compare the achievement rate of HbA1c(≤7%) between the two groups at 12-week of follow-up. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The achievement rate of HbA1c(≤6.5%) | To compare the achievement rate of HbA1c(≤6.5%) between the two groups at 12-week of follow-up. | 12 weeks | 
| The extent of change of HbA1c | To compare the extent of change of HbA1c between the two groups at 12-week of follow-up. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Type 2 diabetes mellitus, glycated albumin, intervention, anti-diabetic regimens, Hemoglobin A1c