Preservation of Beta-cell Function in Type 2 Diabetes Mellitus

The study evaluates the rate beta-cell function decline in newly diagnosed type 2 diabetic patients on two different treatment regimens: insulin and metformin versus glyburide, metformin and pioglitazone.

Study Overview

• Status: Completed
• Conditions: Type 2 Diabetes Mellitus
• Intervention / Treatment: Drug: Metformin; Drug: Insulin; Drug: Metfomin; Drug: Pioglitazone; Drug: glyburide

Detailed Description

This is a 72 months long randomized clinical trial longitudinally evaluating beta-cell function, as well as glycemic control and inflammatory markers in newly diagnosed type 2 diabetic patients on two different treatment regimens: insulin and metformin versus glyburide, metformin and pioglitazone.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• type 2 diabetes mellitus diagnosed within the prior 2 months
• HbA1c > 7% at the time of inclusion
• willing to perform intensive diabetes management
• able to comply with treatment and follow-up regimen

Exclusion Criteria:

• HbA1c > 8% at time of randomization
• creatinine > 1.5 mg/dl
• liver function tests > 3 times the upper limit of normal
• severe anemia
• severe proliferative retinopathy
• NYHA class III or IV heart failure
• active CAD or recent (within 6 months) MI
• pregnant, willing to get pregnant, or not willing to practice any contraceptive method
• non-english speaking
• active heavy alcohol or illicit drug users (within past 6 months)
• history of lactic acidosis

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: Metfomin and Insulin; Metformin 1000mg/BID and Insulin Novolog 70/30 per protocol titration	Drug: Metformin; Metformin 1000mg/BID; Drug: Insulin; Insulin Novolg 70/30 per protocol titration
Active Comparator: Metformin, Pioglitazone and Glyburide; Metformin 1000mg/BID, Pioglitazone 45 mg and glyburide per protocol titration	Drug: Metfomin; Metformin 1000mg/BID; Drug: Pioglitazone; Pioglitazone 45mg; Drug: glyburide; Glyburide per protocol titration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta-cell Function - C-peptide AUC (Area Under the Curve)	C-peptide AUC during a 3-hours mixed meal challenge testing	72 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity as Measure be Matsuda Index	C-peptide-based Matsuda index using following formula: Matsuda index = 500,00 / root square [(fasting c-peptide x fasting glucose x 333) x (average c-peptide 0-120 mins x average glucose 0-120 mins x 333). Higher the Matsuda index, better the insulin sensitivity.	72 months
Bet-cell Function Measured by Disposition Index	Disposition index was measured by multiplying the insulin secretion (C-peptide AUC/C-peptide AUC glucose) by the Matsuda index. Disposition index reflects the beta-cell function adjusted for total body insulin sensitivity	72 months
Weight	Body Weight	72 months
Inflammatory Markers - hsCRP	Inflammatory markers - hsCRP (C reactive protein)	72 months
Inflammatory Markers -Fibrinogen	Inflammatory markers - Fibrinogen	72 months
Inflammatory Markers - PAI-1	Inflammatory markers - PAI-1 (Plasminogen activator inhibitor type 1)	72 months
Quality of Life Survey (QoL) - Current Health Perception	Current health perception was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 = much better than 3 months ago; 2 - Somewhat better now than 3 months ago; 3 - About the same; 4 - Somewhat worse now than 3 months ago; 5 Much worse now than 3 months ago.	72 months
Quality of Life Survey (QoL) - Treatment Satisfaction	Treatment satisfaction was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.	72 months
Quality of Life Survey (QoL) - Treatment Impact	Treatment impact was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - very satisfied; 2 - moderately satisfied; 3 - neither satisfied nor dissatisfied; 4 - moderately dissatisfied; 5 - very dissatisfied.	72 months
Quality of Life Survey (QoL) - Social or Vocational Worry	Social or vocational worry was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 0-5, where 0 - does not apply; 1 - never; 2 - seldom; 3 - sometimes; 4 - often; 5 - all of the time.	72 months
Quality of Life Survey (QoL) - Hypoglycemia Fear	Hypoglycemia fear was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1-5, where 1 - never worry; 2 - rarely water; 3 - sometimes worry; 4 - often worry; 5 - very often worry	72 months
Quality of Life Survey (QoL) - Glycemia Control Perception	Glycemia control perception was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1-7, where 1 - extremely controlled and 7 - not at all controlled.	72 months
Quality of Life Survey (QoL) - Lifestyle Flexibility	Lifestyle flexibility was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1 - a great deal of choice; 2 - a lot of choice; 3 - some choice; 4 - a little choice; 5 - no choice.	72 months
Quality of Life Survey (QoL) - Social Stigma	Social stigma was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a Likert scale score of 1 to 5, where 1- strongly agree; 2 - somewhat agree; 3 - neither agree nor disagree; 4 - somewhat disagree; 5 - strongly disagree.	72 months
Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment	Satisfaction with insulin treatment was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely satisfied to 7 - not at all satisfied.	72 months
Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment	Willingness to continue insulin treatment was measured at randomization and 72 months later using the modified Diabetes Quality of Life Clinical Trial Questionnaire. This questionnaire addresses several areas with respect to diabetes QoL. Answers are in the form of a scale score of 1 to 7, where 1 extremely willing to 7 - not at all willing.	72 months

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Investigators: Principal Investigator: Philip Raskin, MD, University of Texas; Principal Investigator: Ildiko Lingvay, MD, University of Texas

Publications and helpful links

General Publications

• Lingvay I, Kaloyanova PF, Adams-Huet B, Salinas K, Raskin P. Insulin as initial therapy in type 2 diabetes: effective, safe, and well accepted. J Investig Med. 2007 Mar;55(2):62-8. doi: 10.2310/6650.2007.06036.
• Harrison LB, Adams-Huet B, Raskin P, Lingvay I. beta-cell function preservation after 3.5 years of intensive diabetes therapy. Diabetes Care. 2012 Jul;35(7):1406-12. doi: 10.2337/dc11-2170.
• Lingvay I, Legendre JL, Kaloyanova PF, Zhang S, Adams-Huet B, Raskin P. Insulin-based versus triple oral therapy for newly diagnosed type 2 diabetes: which is better? Diabetes Care. 2009 Oct;32(10):1789-95. doi: 10.2337/dc09-0653. Epub 2009 Jul 10.

Study record dates

Study Major Dates

• Study Start: November 1, 2003
• Primary Completion (Actual): December 1, 2011
• Study Completion (Actual): December 1, 2011

Study Registration Dates

• First Submitted: September 30, 2005
• First Submitted That Met QC Criteria: September 30, 2005
• First Posted (Estimate): October 4, 2005

Study Record Updates

• Last Update Posted (Actual): December 14, 2017
• Last Update Submitted That Met QC Criteria: November 17, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: Newly diagnosed; Beta-cell function; TYpe 2 diabetes mellitus
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin; Pioglitazone; Glyburide
• Other Study ID Numbers: 1003-623