Study To Evaluate Beta Cell Function and Glycemic Outcome by Intensive Insulin Therapy

Study Overview
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Brief Summary
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This randomized controlled prospective study aims to evaluate the efficacy of intensive insulin therapy for long term glycemic control and improvement or preservation of beta cell function in newly diagnosed type 2 diabetes patients.

Detailed Description
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Type 2 diabetes is associated with beta cell dysfunction and insulin action at diagnosis of diabetes. Although the relative importance of these two alterations is controversial, growing evidence is swinging to the concept that there is no hyperglycemia without β-cell dysfunction. Also there is agreement that deterioration of glucose tolerance over time is associated with a progressive decrease of beta cell function. Beside the role of genetic factor, the continuous decline in β-cell function is affected by glucotoxicity generated by hyperglycemia and lipotoxicity due to high fatty acid. A vicious cycle of hyperglycemia per se further impairs and may destroy β-cell. Recently, many reports have shown that early intensive glycemic control plays a role in the prevention of progressive ß-cell function and worsening of diabetes. Some studies have shown that early intensive insulin therapy(IIT) to achieve near normoglycemia in new onset type 2 diabetes gives short term and long term improvement in glycemic control after discontinuation of insulin. It is suggested that long term glycemic control is associated with improvement of β-cell function. In the unpublished previous pilot study, the investigators found that early intensive insulin therapy using multiple daily injection (MDI) or daily twice injection in newly diagnosed type 2 diabetes can significantly improve the beta cell function and facilitate further long term glycemic control. To establish the effectiveness of intensive insulin therapy for long term glycemic control and improvement of β-cell function, the investigators will perform a randomized controlled prospective study in newly diagnosed type 2 diabetes in Korea.

Official Title
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The Effect of Intensive and Short-term Insulin Treatment on Long-term Pancreatic β-cell Function in Newly Diagnosed People With Type 2 Diabetes in Korea

Conditions
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Type 2 Diabetes Mellitus, Pancreatic Beta Cell Function, Glucotoxicity

Intervention / Treatment
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* Drug: intensive insulin group
* Drug: Oral AntiDiabetic Drug (glimepiride and metformin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Newly diagnosed drug naïve type 2 diabetic patient with typical diabetic symptom (polydipsia, polyuria, unexplained weight loss) within recent 1 year Initial HbA1c : 8.0 % ≤ HbA1c < 12.0% Exclusion Criteria: Known contraindication to insulin glargine, insulin glulisine, metformin, glimepiride Patients with proliferative diabetic retinopathy Severe liver disease or AST, ALT ≥ 2.5 x ULN History of lactic acidosis Unstable or severe angina Congestive heart failure Chronic disease treated with continuous corticosteroid therapy Diagnosis of cancer Positive urine pregnancy test or plan to become pregnant during the clinical trial

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: Oral AntiDiabetic Drug<br>glimepiride and metformin and/or once daily glargine | Drug: Oral AntiDiabetic Drug (glimepiride and metformin)<br>* glimepiride and metformin combined therapy<br>* Other names: metformin(diabex);|
| Experimental: intensive insulin group<br>insulin glargine insulin glulisine | Drug: intensive insulin group<br>* Once daily long acting insulin and preprandial rapid acting insulin injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Long-term glycemic control |  | up to 2 years | 
| Change of pancreatic beta cell function |  | up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inflammatory marker and insulin sensitivity |  | up to 2 years | 
| Time to reach target goal of blood glucose level |  | up to 2 year | 

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