| City: |
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Bethesda |
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State:
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MD |
| Zip Code: |
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20892 |
| Conditions: |
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Obesity - Insulin Resistance - Overweight - Diabetes Mellitus, Type 2 |
| Purpose: |
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This study will determine whether resting beta cells (cells in the pancreas that produce
insulin) for 2 weeks will improve the ability of patients with Type 2 diabetes mellitus
(T2DM) to make insulin. Beta cells can rest by giving patients insulin shots. The study
will also examine how teenagers with T2DM feel about having diabetes and explore differences
between young people with and without T2DM.
This study includes patients 12 to 25 years of age with T2DM who are overweight and who were
diagnosed within 2 years of enrolling in the study. Healthy individuals of normal weight or
who are overweight are also eligible. Candidates are screened with a medical history,
physical examination and laboratory tests.
Participants with T2DM are assigned to one of two groups. Group 1 takes an anti-diabetes
medicine called metformin and follows a diet prescribed by a study staff dietitian for 2
weeks. Group 2 takes metformin, follows the prescribed diet, and receives insulin through a
pump under the skin for 2 weeks. During these two weeks, all participants have the following
tests:
- Frequent blood sugar checks.
- Oral glucose tolerance test (routine diabetes test in which blood samples are drawn
before and several times after the subject drinks a sugary solution).
- Arginine stimulation to test the response of the body to arginine, a normal ingredient
of food that stimulates the release of insulin. Two catheters are placed into veins in
the arms, one to administer a liquid containing arginine, the other to draw the blood
samples.
- Ultrasound of the blood vessels in the neck to check for hardening of the arteries.
- Metabolism test to measure the amount of oxygen used during rest. The subject breathes
normally during rest while wearing a canopy over his or her head for about 20 minutes.
- MRI scans of the abdomen to examine the amount of fat in the belly (at the beginning
and end of the study)
- DEXA scan to determine percent body fat.
- Tests to explore quality of life and feelings about health, work or school, friends and
family.
- Exercise testing on a treadmill or stationary bicycle.
- Genetic studies for information on diabetes and obesity.
Normal volunteers have blood draws, oral glucose tolerance testing, MRI scan, DEXA scan,
psychological testing, exercise testing, and genetic testing.
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| Study summary: |
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Background:
Type 2 diabetes mellitus (T2DM) is a condition characterized by insulin resistance and
progressive failure of the insulin-secreting beta-cells. Previously considered a disease of
adults, it is now becoming increasingly prevalent in children and adolescents. Patients with
childhood onset T2DM are at very high risk for diabetes-related morbidity and mortality, due
to a longer life-time duration of diabetes, as well as possible increased rapidity of
beta-cell failure.
In part, the impairment in insulin secretion is caused by beta-cell exhaustion due to a
constant, unsuccessful attempt to compensate for the existing insulin resistance. In
addition, beta-cell function is affected by glucotoxicity, generating a downward cycle of
hyperglycemia leading to decreased insulin secretion, which further worsens hyperglycemia.
Results from two recent studies in adults with newly diagnosed T2DM suggest that intensive
insulin treatment for 2 weeks may break this cycle, resulting in significant, long-term
improvement of beta-cell function. Both reports documented that approximately 50 percent of
patients maintained euglycemia on diet alone at 12-month follow-up.
Aims:
In this study, we will address the following questions:
1. Does short-term beta-cell rest induced by intensive insulin therapy result in prolonged
improvement in beta-cell function in adolescents and young adults with T2DM compared to
patients who receive conventional treatment?
2. What mechanisms underlie the improvement of beta-cell function through beta-cell rest?
Methods:
In this randomized, controlled trial we will divide adolescents and young adults with T2DM
of less than or equal to 2 years duration into 2 treatment groups:
Group 1 (control arm) will receive conventional therapy for T2DM (metformin plus diet and
behavior modification).
Group 2 will undergo beta-cell rest using continuous subcutaneous insulin infusion (CSII)
for a period of 2 weeks, in addition to conventional therapy (metformin plus diet and
behavior modification).
The primary outcome will be comparison of insulin secretion (assessed at one year) in the
beta-cell rest group versus the conventional group. |
| Criteria: |
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- DIABETIC SUBJECTS:
INCLUSION CRITERIA:
1. Clinical diagnosis of type 2 diabetes.
2. Duration of diabetes less than or equal to 2 years (since diagnosis)
3. BMI greater than or equal to 85th percentile for age
4. Age 12-25 years at enrollment
EXCLUSION CRITERIA:
1. Normal OGTT at NIH (fasting blood glucose less than 100 mg/dL AND 2-hour blood
glucose less than 140 mg/dL)
2. Monogenic causes of diabetes (e.g. maturity-onset diabetes of the young [MODY] or
mitochondrial diabetes). Subjects will be excluded if there is a known personal or
family (first degree relative) history of monogenic diabetes. Genetic testing for
monogenic causes of diabetes will be performed on potential subjects if the family
history is suggestive of monogenic diabetes.
3. Significant comorbidity that, in the opinion of the investigators, will increase risk
to the subject, such as coronary artery disease or any heart disease that increases
risk associated with exercise (e.g. hypertrophic obstructive cardiomyopathy), renal
impairment with serum creatinine greater than 1.4 mg/dL, or current treatment for
cancer. Specific obesity-related comorbidities are explicitly permitted, including
hypertension, hyperlipidemia, obstructive sleep apnea and non-alcoholic
steatohepatitis.
4. Current use of insulin
5. Current use of prescription or non-prescription weight-loss drugs
6. Positive urine pregnancy test or plans to become pregnant during the clinical trial
7. Known allergy, sensitivity or other contraindication to any study drug or its vehicle
8. Psychiatric or cognitive disorder that will, in the opinion of the investigators,
limit the subject's ability to comply with study medications and monitoring
MATCHED VOLUNTEERS:
INCLUSION CRITERIA:
Two types of volunteers will be recruited:
1. Age, sex, race and BMI matched with study enrollees who have T2DM
2. Normal weight (BMI between 5th and 85th percentiles for age) volunteers who are age,
sex and race matched to subjects with T2DM
EXCLUSION CRITERIA:
1. Diabetes and impaired glucose tolerance
2. Significant comorbidity that, in the opinion of the investigators, will increase risk
to the subject (specific obesity-related comorbidities are explicitly permitted,
including hypertension, hyperlipidemia, obstructive sleep apnea and non-alcoholic
steatohepatitis)
3. Current or recent (past 2 months) use of drugs that alter glucose metabolism (e.g.
metformin)
4. Current use of prescription or non-prescription weight-loss drugs
5. Positive urine pregnancy test |
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| Study is available at: |
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National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, MD 20892
United States
Primary Contact:
Patient Recruitment and Public Liaison Office
Email: prpl@mail.cc.nih.gov
Phone: (800) 411-1222 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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March 22, 2011 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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