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

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

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.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus; Pancreatic Beta Cell Function; Glucotoxicity
• Intervention / Treatment: Drug: Oral AntiDiabetic Drug (glimepiride and metformin); Drug: intensive insulin group

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In the unpublished previous pilot study, the investigators found that early intensive insulin therapy using multiple daily injection (MDI) or daily twice injection in newly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.

• Study Type: Interventional
• Enrollment (Actual): 112
• Phase: Phase 4

Contacts and Locations

Study Locations

• Korea, Republic of
  • Bucheon, Korea, Republic of
    • The Catholic University of Korea Bucheon St.Mary's Hospital
  • In Cheon, Korea, Republic of, 400-711
    • Inha University Hospital
  • Jeju-do, Korea, Republic of
    • Jeju National University Hospital
  • Seoul, Korea, Republic of, 130-702
    • Kyunghee University Medical Center
  • Seoul, Korea, Republic of, 152-730
    • Korea University Guro Hospital
  • Seoul, Korea, Republic of
    • Kyung Hee University East Weast Neo Medicalcenter
  • Suwon, Korea, Republic of, 443-721
    • Ajou University Medical Center
  • Kyunggi-do
    • Kuri, Kyunggi-do, Korea, Republic of, 471-020
      • Hanyang University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Oral AntiDiabetic Drug; glimepiride and metformin and/or once daily glargine	Drug: Oral AntiDiabetic Drug (glimepiride and metformin); glimepiride and metformin combined therapy; Other Names: glimepiride(amaryl); metformin(diabex)
Experimental: intensive insulin group; insulin glargine insulin glulisine	Drug: intensive insulin group; Once daily long acting insulin and preprandial rapid acting insulin injection

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Kyunghee University Medical Center
• Collaborators: Sanofi; Korea University Guro Hospital; Hanyang University; The Catholic University of Korea; Jeju National University Hospital; Inha University Hospital; Ajou University; East West Neo Medical Center
• Investigators: Principal Investigator: Jeong-taek Woo, MD, PhD, Kyunghee University Medical Center

Study record dates

Study Major Dates

• Study Start: April 1, 2007
• Primary Completion (Actual): August 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: May 16, 2007
• First Submitted That Met QC Criteria: May 16, 2007
• First Posted (Estimate): May 17, 2007

Study Record Updates

• Last Update Posted (Estimate): September 26, 2013
• Last Update Submitted That Met QC Criteria: September 25, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: type 2 diabetes mellitus; intensive insulin therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Immunosuppressive Agents; Immunologic Factors; Hypoglycemic Agents; Metformin; Glimepiride
• Other Study ID Numbers: KIIT-KMC-0701