Type 2 Diabetes Mellitus
Conditions
Keywords
TYpe 2 diabetes mellitus, Newly diagnosed, Beta-cell function
Brief summary
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
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.
Interventions
DRUGMetformin
Metformin 1000mg/BID
DRUGInsulin
Insulin Novolg 70/30 per protocol titration
DRUGMetfomin
Metformin 1000mg/BID
DRUGPioglitazone
Pioglitazone 45mg
DRUGglyburide
Glyburide per protocol titration
Sponsors
University of Texas Southwestern Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Beta-cell Function - C-peptide AUC (Area Under the Curve) | 72 months | C-peptide AUC during a 3-hours mixed meal challenge testing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Bet-cell Function Measured by Disposition Index | 72 months | 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 |
| Weight | 72 months | Body Weight |
| Inflammatory Markers - hsCRP | 72 months | Inflammatory markers - hsCRP (C reactive protein) |
| Inflammatory Markers -Fibrinogen | 72 months | Inflammatory markers - Fibrinogen |
| Inflammatory Markers - PAI-1 | 72 months | Inflammatory markers - PAI-1 (Plasminogen activator inhibitor type 1) |
| Quality of Life Survey (QoL) - Current Health Perception | 72 months | 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. |
| Quality of Life Survey (QoL) - Treatment Satisfaction | 72 months | 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. |
| Insulin Sensitivity as Measure be Matsuda Index | 72 months | 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. |
| Quality of Life Survey (QoL) - Social or Vocational Worry | 72 months | 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. |
| Quality of Life Survey (QoL) - Hypoglycemia Fear | 72 months | 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 |
| Quality of Life Survey (QoL) - Glycemia Control Perception | 72 months | 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. |
| Quality of Life Survey (QoL) - Lifestyle Flexibility | 72 months | 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. |
| Quality of Life Survey (QoL) - Social Stigma | 72 months | 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. |
| Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment | 72 months | 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. |
| Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment | 72 months | 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. |
| Quality of Life Survey (QoL) - Treatment Impact | 72 months | 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. |
Countries
United States
Participant flow
Recruitment details
Patients recruited at UT Southwestern Clinical Diabetes Research Office
Pre-assignment details
A 3-months run-in period preceeded randomization. During this period all patients were treated with insulin and metformin.
Participants by arm
| Arm | Count |
|---|---|
| Metfomin & Insulin Insulin NovoLog 70/30 BID adjusted to target fasting blood glucose level of 70 to 110 mg/dL and postprandial blood sugar \< 140 mg/dL and Metformin 2,000 mg/day (or maximum tolerated dose). | 29 |
| Metfomin, Pioglitazone & Glyburide Metformin 2,000 mg (or maximum tolerated dose); glyburide 1.25 mg BID and 15 mg daily pioglitazone (pioglitazone was titrated monthly to a final dose of 45 mg daily). | 29 |
| Total | 58 |
Baseline characteristics
| Characteristic | Metfomin, Pioglitazone & Glyburide | Metfomin & Insulin | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 29 Participants | 29 Participants | 58 Participants |
| Age, Continuous | 45.0 years STANDARD_DEVIATION 10.7 | 44.8 years STANDARD_DEVIATION 9.7 | 44.9 years STANDARD_DEVIATION 10.1 |
| Region of Enrollment United States | 29 participants | 29 participants | 58 participants |
| Sex: Female, Male Female | 12 Participants | 9 Participants | 21 Participants |
| Sex: Female, Male Male | 17 Participants | 20 Participants | 37 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 5 / 29 | 6 / 29 |
| serious Total, serious adverse events | 1 / 29 | 1 / 29 |
Outcome results
Primary
Beta-cell Function - C-peptide AUC (Area Under the Curve)
C-peptide AUC during a 3-hours mixed meal challenge testing
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Beta-cell Function - C-peptide AUC (Area Under the Curve) | 2096 ng*min/mL | Standard Deviation 795 |
| Metformin, GLyburide & Pioglitazone | Beta-cell Function - C-peptide AUC (Area Under the Curve) | 1725 ng*min/mL | Standard Deviation 618 |
Secondary
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
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Bet-cell Function Measured by Disposition Index | 0.12 index | Standard Deviation 0.07 |
| Metformin, GLyburide & Pioglitazone | Bet-cell Function Measured by Disposition Index | 0.16 index | Standard Deviation 0.09 |
Secondary
Inflammatory Markers -Fibrinogen
Inflammatory markers - Fibrinogen
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Inflammatory Markers -Fibrinogen | 399.0 mg/dL | Standard Deviation 82.6 |
| Metformin, GLyburide & Pioglitazone | Inflammatory Markers -Fibrinogen | 395.4 mg/dL | Standard Deviation 98.5 |
Secondary
Inflammatory Markers - hsCRP
Inflammatory markers - hsCRP (C reactive protein)
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Inflammatory Markers - hsCRP | 6.9 mg/L | Standard Deviation 7.7 |
| Metformin, GLyburide & Pioglitazone | Inflammatory Markers - hsCRP | 6.1 mg/L | Standard Deviation 8.9 |
Secondary
Inflammatory Markers - PAI-1
Inflammatory markers - PAI-1 (Plasminogen activator inhibitor type 1)
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Inflammatory Markers - PAI-1 | 13.9 IU/L | Standard Deviation 11.7 |
| Metformin, GLyburide & Pioglitazone | Inflammatory Markers - PAI-1 | 16.7 IU/L | Standard Deviation 18 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Insulin Sensitivity as Measure be Matsuda Index | 3.12 index | Standard Deviation 2.62 |
| Metformin, GLyburide & Pioglitazone | Insulin Sensitivity as Measure be Matsuda Index | 2.45 index | Standard Deviation 1.09 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Current Health Perception | 2.7 score on a scale | Standard Deviation 0.9 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Current Health Perception | 2.9 score on a scale | Standard Deviation 0.9 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Glycemia Control Perception | 2.8 score on a scale | Standard Deviation 2.8 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Glycemia Control Perception | 2.0 score on a scale | Standard Deviation 2 |
Secondary
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
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Hypoglycemia Fear | 1.8 score on a scale | Standard Deviation 0.3 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Hypoglycemia Fear | 1.8 score on a scale | Standard Deviation 0.4 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Lifestyle Flexibility | 2.1 score on a scale | Standard Deviation 0.6 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Lifestyle Flexibility | 2.0 score on a scale | Standard Deviation 0.6 |
Secondary
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.
Time frame: 72 months
Population: Data were not collected from participants in the Metfomin, Pioglitazone \& Glyburide Arm/Group since patients did not receive insulin.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Satisfaction With Insulin Treatment | 1.2 score on a scale | Standard Deviation 0.9 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Social or Vocational Worry | 1.8 score on a scale | Standard Deviation 0.3 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Social or Vocational Worry | 1.7 score on a scale | Standard Deviation 0.3 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Social Stigma | 2.2 score on a scale | Standard Deviation 1.2 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Social Stigma | 2.2 score on a scale | Standard Deviation 1.7 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Treatment Impact | 1.7 score on a sale | Standard Deviation 0.2 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Treatment Impact | 1.8 score on a sale | Standard Deviation 0.3 |
Secondary
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.
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Treatment Satisfaction | 1.7 score on a scale | Standard Deviation 0.5 |
| Metformin, GLyburide & Pioglitazone | Quality of Life Survey (QoL) - Treatment Satisfaction | 2.1 score on a scale | Standard Deviation 0.8 |
Secondary
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.
Time frame: 72 months
Population: Data were not collected from participants in the Metfomin, Pioglitazone \& Glyburide Arm/Group since patients did not receive insulin.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Quality of Life Survey (QoL) - Willingness to Continue Insulin Treatment | 1.4 score on a scale | Standard Deviation 0.7 |
Secondary
Weight
Body Weight
Time frame: 72 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Metformin & Insulin | Weight | 107.7 kg | Standard Deviation 31.1 |
| Metformin, GLyburide & Pioglitazone | Weight | 107.9 kg | Standard Deviation 31.4 |