Preservation of Beta-cell Function in Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Preservation of Beta-cell Function in Type 2 Diabetes Mellitus

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: Metformin
* Drug: Insulin
* Drug: Metfomin
* Drug: Pioglitazone
* Drug: glyburide


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 65 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: Metfomin and Insulin<br>Metformin 1000mg/BID and Insulin Novolog 70/30 per protocol titration | Drug: Metformin<br>* Metformin 1000mg/BID<br>Drug: Insulin<br>* Insulin Novolg 70/30 per protocol titration<br>|
| Active Comparator: Metformin, Pioglitazone and Glyburide<br>Metformin 1000mg/BID, Pioglitazone 45 mg and glyburide per protocol titration | Drug: Metfomin<br>* Metformin 1000mg/BID<br>Drug: Pioglitazone<br>* Pioglitazone 45mg<br>Drug: glyburide<br>* Glyburide per protocol titration<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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TYpe 2 diabetes mellitus, Newly diagnosed, Beta-cell function