Evaluation of the Effects of Different Interventions on Glycemic Control in Newly-Diagnosed Type 2 Diabetic Patients

Study Overview
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Brief Summary
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The purpose of this study is to investigate and evaluate the effects of different interventions (1.continuous subcutaneous insulin infusion,2.multiple daily injections, 3.anti-hyperglycemic agents) on glycemic control, B-cell function and the remission rate in newly-diagnosed type 2 diabetic patients.

Detailed Description
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ß-Cell dysfunction and decreased insulin sensitivity are the main pathophysiological defects responsible for the development of hyperglycemia. With continuous presence of insulin resistance, progressive loss of ß-cell function is the crucial defect. Hyperglycemia has deleterious effect on β-cell function, which is partially reversible by adequate glycemic control. In newly diagnosed type 2 diabetic patients with severe hyperglycemia, 2 weeks continuous subcutaneous insulin infusion (CSII) can induce adequate glycemic control with improvement of β-cell function. Nearly half of the patients can maintain euglycemia longer than 12 months by transient CSII. The improvement of β-cell function, especially the restoration of the first-phase insulin response is related to sustained euglycemia in the newly diagnosed type 2 diabetic patients. But it is unclear whether any other interventions (such as oral hypoglycemic agents and multiple daily injections) inducing optimal glycemic control in a short period of time can have the same effect. As a multicenter, open-label, randomized, parallel-group study will be needed to further prove and clarify the findings.

Official Title
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Evaluation of the Effects of Oral Anti-Hyperglycemic Agents, Multiple Daily Injections or Continuous Subcutaneous Insulin Infusion on Glycemic Control, B-Cell Function and the Remission Rate in Newly-Diagnosed Type 2 Diabetic Patients

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Human Insulin (Novolin-R, Novo Nordisk)
* Device: H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland
* Other: Pre-meal
* Drug: Novolin-R
* Drug: Human Insulin NPH (Novolin-N, Novo Nordisk)
* Drug: Gliclazide (Diamicron, Servier)
* Drug: Diamicron and Glucophage


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: informed consents be given before treatment the newly-diagnosed type 2 diabetic patients fasting blood glucose (FBG) level ranging from 7.0～16.7 mmol/L age ranging from 25～70 years old body mass index (BMI) ranging from20～35kg/m2 never be treated with any anti-hyperglycemic agents or anti-hyperlipidemic agents Exclusion Criteria: having any severe acute or chronic complications renal dysfunction, blood creatinine≥150µmol/L blood aminotransferase level rising up(more than 2 times of the normal level) any severe cardiac disease including congestive cardiac failure, unstable angina and myocardial infarct in 12 months serious hypertension (systolic pressure≥180mmHg and/ or diastolic pressure≥110mmHg) chronic or acute pancreatic disease severe systematic diseases or malignant tumor allergic to the drugs using in the trial any factors interfering the result female patients incline to be pregnant being treated with corticosteroid, immunosuppressing drugs or cytotoxic drugs poor compliance

Ages Eligible for Study
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Minimum Age: 25 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: CSII<br>Patients in continuous subcutaneous insulin infusion group received Human Insulin (Novolin-R, Novo Nordisk) with an insulin pump (H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland); | Drug: Human Insulin (Novolin-R, Novo Nordisk)<br> <br> Device: H-Tron Plus V100; Disetronic Medical System, Burgdorf, Switzerland<br> <br> |
| Active Comparator: MDI<br>Patients in MDI group were treated with pre-meal Novolin-R, and Human Insulin NPH (Novolin-N, Novo Nordisk) at bedtime. Initial insulin doses were 0.4-0.5 IU/kg and total daily doses were divided into 50% of basal and 50% of bolus injection in CSII group and 30%-20%-20%-30% in multiple daily insulin injection group | Other: Pre-meal<br> <br> Drug: Novolin-R<br> <br> Drug: Human Insulin NPH (Novolin-N, Novo Nordisk)<br> <br> |
| Active Comparator: OHA<br>In oral hpoglycemic agents group, the patients with 20 kg/m2<BMI≤25kg/m2 were initiated with Gliclazide (Diamicron, Servier) 80mg Bid (maximum to 160mg Bid), the patients with 25kg/m2<BMI≤35kg/m2 were initiated with Metformin (Glucophage, BMS) 0.5 Bid (maximum to 2.0g/d), the combination of Diamicron and Glucophage was used in patients who could not achieve glycaemic control goal with one OHA or with FPG≥11.1mmol/l at randomization | Drug: Gliclazide (Diamicron, Servier)<br> <br> Drug: Diamicron and Glucophage<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| glycemic control, the improvement of β-cell l function and the remission rate after short intensive therapy in newly diagnosed type 2 diabetic patients |  | Oct. 2007 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the effects of different interventions (oral anti-hyperglycemic agents, multiple daily injections and continuous subcutaneous insulin infusion) on glycemic control, β-cell function and the remission rate in newly-diagnosed type 2 diabetic patients |  | Oct. 2007 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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type 2 diabetes mellitus, therapy, sulfonylureas, metformin, insulin