Diabetes Mellitus, Type II
Conditions
Keywords
Type II Diabetes Mellitus, Diabetes, PET, Heart Metabolism, Lovaza
Brief summary
Type 2 Diabetes Mellitus (T2DM) is a disease that interferes with the body's proper production and use of insulin, a hormone needed to convert sugar into usable energy. People with Type 2 Diabetes Mellitus (T2DM) are at a higher risk for certain cardiovascular diseases, including heart disease and stroke. Normal treatments for Type 2 Diabetes Mellitus (T2DM) target blood sugar levels only, but there is reason to believe that also targeting blood fat levels will improve both sugar metabolism and heart function in people with Type 2 Diabetes Mellitus, (T2DM.) This study will determine the effectiveness of blood-fat lowering treatments along with blood-sugar control treatments in improving heart function and symptoms of people with Type 2 Diabetes Mellitus(T2DM), and if this varies between men and women.
Detailed description
Type 2 Diabetes Mellitus, (T2DM) is the most common type of diabetes. In Type 2 Diabetes Mellitus (T2DM), the body does not properly process sugars and, as a result, there is an excess amount of sugar in the blood. Eventually, the high blood sugar levels can lead to heart disease, nerve damage, kidney problems, or blindness. Typical Type 2 Diabetes Mellitus (T2DM) treatments target maintenance of blood sugar levels. Previous studies on Type 2 Diabetes Mellitus (T2DM) have indicated that in people who have high amounts of fats in the blood, the body relies more heavily on fats than sugars as an energy source. This dependence on fats for energy has been shown to have a negative effect on heart function. There is reason to believe that lowering the levels of fats in the blood will enhance the ability of the heart and the whole body to efficiently use both fats and sugars as energy sources. This study will evaluate the effectiveness of treatment strategies that are designed to reach target levels of sugar and fat in the blood for treating people with Type 2 Diabetes Mellitus (T2DM). Participation in this double-blind study will last between 4 and 6 months. First, participants will undergo a medical screening and medication adjustment period, expected to last 6 months. The medical screening, lasting about 1 hour, will involve completing a medical history, physical exam, pregnancy test if applicable, and blood test to measure various factors that contribute to diabetes control. Participants will also be asked permission to store 1 tablespoon of their blood for up to 10 years to be used in future studies concerning genetics and heart energy metabolism. During the medication adjustment period, study physicians will adjust the participants' medications, offer advice on diabetes education and nutrition, and record any side effects from the medications. For newly diagnosed Type 2 Diabetes Mellitus (T2DM) participants, the study physician may recommend medication changes to assure a hemoglobin A1c (HgA1c) level of less than 7.5%. If participants have already achieved this level, they will be asked to continue present medications and to also begin taking the medication metformin for the 30 days before they undergo several imaging studies. Next, participants will complete routine tests that evaluate the pumping function of the heart, including an electrocardiogram (ECG) performed before and during exercise, a body composition study using a dual energy x-ray absorptiometry (DEXA) scan, and a magnetic resonance imaging (MRI) test. Each of these tests will last between 30 and 90 minutes. After the qualifying tests, participants will return for the first of two separate imaging days that will include the same tests. The second imaging day will occur at the end of the medication period, approximately 2 months after the first imaging day. The first tests will be a whole body metabolism study and a heart metabolism imaging study, performed simultaneously. The whole body metabolism study will involve the injection of two tracers of metabolism, one for glucose and one for fatty acids. The heart metabolism imaging study will involve a positron-emission tomographic (PET) scan to take pictures of the heart and will include blood draws. The final imaging test will be a resting echocardiogram (ECHO) to measure heart function. Following completion of the first day of imaging tests, participants will be randomly assigned to one of three possible treatment groups: Group A ,B, or C. Group A will take Metformin alone.Group B will take Metformin and Rosiglitazone. Group C will take Metformin and Lovaza. Participants will be seen monthly for the next 4 months, during which study medication will be distributed and blood pressure, heart rate, weight, and any side effects, such as lower extremity swelling, will be measured. If there is a noticeable increase in swelling, study physicians may adjust medication dosages. During visits at Months 2 and 4, blood samples will be taken to measure liver and organ function and HgA1c. At the completion of the 4-month medication treatment, participants will undergo repeat imaging tests. If needed, participants will be offered the opportunity to attend one or more follow-up visits to re-establish a medication routine.
Interventions
DRUGMetformin
Metformin is taken alone
DRUGRosiglitazone
Rosiglitizone is taken with Metformin
DRUGLovaza
Lovaza is taken with Metformin
Sponsors
Washington University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Meets Americans with Disabilities Act (ADA) criteria for T2DM; if newly diagnosed, must have fasting blood glucose greater than 126 mg/dl on two occasions, a random blood glucose greater than 200 mg/dl with symptoms, or a diagnostic oral glucose tolerance test * Weight of less than 350 pounds * Hemoglobin A1c of equal to or less than 7.5% at study entry or willing to go on one of the following therapies to achieve necessary percentage: metformin monotherapy greater than 1000 mg daily for at least 30 days or metformin greater than 1000 mg daily plus any combination of sulfonylurea, glipizide, or alpha-glucosidase inhibitor * Blood pressure less than 140/90 mm Hg at study entry * LDL level less than 130 mg/dL if on stable lipid lowering regimen * Willing to undergo normal rest/stress (treadmill or dobutamine) echocardiogram * If currently taking thyroid replacement therapy, must be on a stable dose of thyroid replacement and must have a thyroid function blood test that is in the normal range * Willing to use an effective form of birth control throughout the study
Exclusion criteria
* Received therapy with an insulin sensitizer of the thiazolidinedione class within 6 months prior to study entry * Required insulin therapy for more than 2 weeks in the year prior to study entry * History of angina, heart attack, coronary artery bypass grafting (CABG), stroke, congestive heart failure (CHF), or peripheral vascular disease (PVD) * Known coronary artery disease (CAD) with residual lesions of greater than 50% * Current smoker * Use or expected use of corticosteroids in any form * Serum triglycerides greater than 400 mg/dl on a fasting sample at study entry * Any contraindication to a thiazolidinedione (TZD) insulin sensitizer, metformin, or other drugs likely to be used during the study * Liver disease with liver function test (LFT) greater than 2 times the upper limit of normal (ULN) * Serum creatinine greater than 1.5 mg/dl for women and 1.6 mg/dl for men OR greater than 2+ proteinuria on urine dipstick
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Percent Change in Plasma Triglycerides | Baseline and 3 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Metformin and Lovaza Participants assigned to take metformin and Lovaza
Lovaza: Dosage of 4 g to be taken daily for 2 months
Metformin: Dosage of at least 1000 mg to be taken daily for 4 months | 28 |
| Metformin Participants assigned to take metformin and placebo
Metformin: Dosage of at least 1000 mg to be taken daily for 4 months | 27 |
| Metformin and Rosiglitizone Participants assigned to take Metformin and Rosiglitizone | 23 |
| Total | 78 |
Baseline characteristics
| Characteristic | Total | Metformin | Metformin and Rosiglitizone | Metformin and Lovaza |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 78 Participants | 27 Participants | 23 Participants | 28 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — | — |
| Region of Enrollment United States | 78 Participants | 27 Participants | 23 Participants | 28 Participants |
| Sex: Female, Male Female | 43 Participants | 15 Participants | 15 Participants | 13 Participants |
| Sex: Female, Male Male | 35 Participants | 12 Participants | 8 Participants | 15 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 28 | 0 / 27 | 0 / 23 |
| other Total, other adverse events | 0 / 28 | 0 / 27 | 0 / 23 |
| serious Total, serious adverse events | 0 / 28 | 0 / 27 | 0 / 23 |
Outcome results
Primary
Percent Change in Plasma Triglycerides
Time frame: Baseline and 3 months
Population: Data presented are stratified by sex
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Metformin and Lovaza | Percent Change in Plasma Triglycerides | Plasma triglycerides women | -2.0 percent change | Standard Deviation 12 |
| Metformin and Lovaza | Percent Change in Plasma Triglycerides | Plasma triglycerides men | -5.0 percent change | Standard Deviation 12 |
| Metformin | Percent Change in Plasma Triglycerides | Plasma triglycerides women | 16.0 percent change | Standard Deviation 30 |
| Metformin | Percent Change in Plasma Triglycerides | Plasma triglycerides men | -10.0 percent change | Standard Deviation 5 |
| Metformin and Rosiglitazone | Percent Change in Plasma Triglycerides | Plasma triglycerides women | -5.0 percent change | Standard Deviation 15 |
| Metformin and Rosiglitazone | Percent Change in Plasma Triglycerides | Plasma triglycerides men | 1.0 percent change | Standard Deviation 12 |