Clinical trial NCT00474838: Study To Evaluate Beta Cell Function and Glycemic Outcome by Intensive Insulin Therapy
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Pancreatic Beta Cell Function
Glucotoxicity
Keywords: type 2 diabetes mellitus
intensive insulin therapy
Lead sponsor: Kyunghee University Medical Center
Sponsor class: OTHER
Collaborators: name: Korea University Guro Hospital
name: Hanyang University
name: Inha University Hospital
name: Ajou University
name: Sanofi
name: East West Neo Medical Center
name: The Catholic University of Korea
name: Jeju National University Hospital
First posted: 2007-05-17
Enrollment: 112
Sex: ALL
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Long-term glycemic control
timeFrame: up to 2 years
measure: Change of pancreatic beta cell function
timeFrame: up to 2 years
Secondary outcomes:
measure: Inflammatory marker and insulin sensitivity
timeFrame: up to 2 years
measure: Time to reach target goal of blood glucose level
timeFrame: up to 2 year
Other outcomes:
Locations:
city: Kuri
country: Korea, Republic of
facility: Hanyang University Medical Center
state: Kyunggi-do
city: Bucheon
country: Korea, Republic of
facility: The Catholic University of Korea Bucheon St.Mary's Hospital
city: In Cheon
country: Korea, Republic of
facility: Inha University Hospital
city: Jeju-do
country: Korea, Republic of
facility: Jeju National University Hospital
city: Seoul
country: Korea, Republic of
facility: Kyunghee University Medical Center
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital
city: Seoul
country: Korea, Republic of
facility: Kyung Hee University East Weast Neo Medicalcenter
city: Suwon
country: Korea, Republic of
facility: Ajou University Medical Center
Study officials:
affiliation: Kyunghee University Medical Center
name: Jeong-taek Woo, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: