Protocol Number: 07-DK-0115

Title:

Effect of Short-Term Beta-Cell Rest in Adolescents and Young Adults with Type 2 Diabetes Mellitus

Number:

07-DK-0115

Summary:

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 and diazoxide (a medicine that blocks cells from releasing insulin). 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 20 years of age with T2DM who are overweight and who were diagnosed within 1 year 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 and diazoxide by mouth for 2 weeks. All patients are hospitalized for this 2-week period. During this time, they 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.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): None

Eligibility Criteria:

DIABETIC SUBJECTS:

INCLUSION CRITERIA:

1. Type 2 diabetes mellitus as defined by:

a. Fasting blood glucose greater than or equal to 126 mg/dL OR postprandial blood sugar greater than or equal to 200 mg/dL (either during OGTT at NIH or as previously documented on outside medical record)

Since subjects may already have been started on treatment with hypoglycemic agents at the time of enrollment, they may have blood glucose levels in the impaired glucose tolerance range (fasting glucose 100-125 mg/dL and postprandial 140-199 mg/dL). This is a sign of adequately controlled diabetes, rather than an incorrect diagnosis of diabetes. Therefore, prior documentation (on outside medical records) of blood glucose values documenting diabetes will be acceptable if the subject has impaired glucose tolerance rather than overt diabetes according to screening results at NIH.

b. Absence of insulin autoantibodies (in insulin naive patients only)

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

Special Instructions:

Currently Not Provided

Keywords:

Children

Adolescents

Teens

Young Adults

Recruitment Keyword(s):

Type 2 Diabetes

Overweight

Obesity

Condition(s):

Obesity

Insulin Resistance

Overweight

Diabetes Mellitus, Type 2

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Metformin

Drug: Insulin

Drug: Diazoxide

Behavioral: Nutrition counseling

Behavioral: Exercise counseling

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Dabelea D, Hanson RL, Bennett PH, Roumain J, Knowler WC, Pettitt DJ. Increasing prevalence of Type II diabetes in American Indian children Diabetologia. 1998 Aug;41(8):904-10.

Fridlyand LE, Philipson LH. Does the glucose-dependent insulin secretion mechanism itself cause oxidative stress in pancreatic beta-cells? Diabetes. 2004 Aug;53(8):1942-8.

Gungor N, Bacha F, Saad R, Janosky J, Arslanian S. Youth type 2 diabetes: insulin resistance, beta-cell failure, or both? Diabetes Care. 2005 Mar;28(3):638-44.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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