Glucotoxicity, Pancreatic Beta Cell Function, Type 2 Diabetes Mellitus
Conditions
Keywords
type 2 diabetes mellitus, intensive insulin therapy
Brief summary
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
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 In the unpublished previous pilot study, the investigators found that early intensive insulin therapy using multiple daily injection (MDI) or daily twice injection in newly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.
Interventions
DRUGintensive insulin group
Once daily long acting insulin and preprandial rapid acting insulin injection
DRUGOral AntiDiabetic Drug (glimepiride and metformin)
glimepiride and metformin combined therapy
Sponsors
Korea University Guro Hospital
Hanyang University
Inha University Hospital
Ajou University
Sanofi
East West Neo Medical Center
The Catholic University of Korea
Jeju National University Hospital
Kyunghee University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Long-term glycemic control | up to 2 years |
| Change of pancreatic beta cell function | up to 2 years |
Secondary
| Measure | Time frame |
|---|---|
| Inflammatory marker and insulin sensitivity | up to 2 years |
| Time to reach target goal of blood glucose level | up to 2 year |
Countries
South Korea
Outcome results
None listed