Effect of Short-Term Beta-Cell Rest in Adolescents and Young Adults With Type 2 Diabetes Mellitus
Condition: Obesity; Overweight; Diabetes Mellitus, Type 2
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2; Overweight
Study type: Observational

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. 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.
    

Detailed description: 
      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.

      Aims:

      In this study, we will address the following aims:

        1. To characterize hormonal, metabolic, and behavioral traits in patients with youth-onset
           type 2 diabetes. These will include:

             1. Assessment of Beta-cell function and insulin resistance

             2. Psychological, demographic, and socioeconomic assessments

             3. Assessment of the physiology and pathophysiology of incretins and other gut
                hormones

             4. Identification of early biomarkers of diabetes complications, especially
                cardiovascular disease

             5. Validation of new methods for studying glucose metabolism

        2. To serve as a recruitment and development tool for hypothesis-driven pilot studies,
           discussed in the appendices of this protocol.

      Methods:

      Children and young adults ages 8 to 25 years with type 2 diabetes will be studied in a
      cross-sectional and longitudinal manner. Two control groups without diabetes will be studied
      for comparison purposes: healthy lean controls, and overweight/obese controls. Methods used
      to study participants include routine blood sampling, oral glucose tolerance testing, mixed
      meal testing, arginine stimulation testing, DEXA, MRI, carotid ultrasound, questionnaires,
      exercise physiology, and measurements of energy expenditure. Patients with type 1 diabetes
      will be studied using oral glucose tolerance and mixed meal tests in a pilot study of
      artificial sweeteners.
    

Intervention name(s): Metformin; Insulin; Nutrition counseling; Exercise counseling
Intervention type(s): Drug; Drug; Behavioral; Behavioral
Intervention MeSH terms: Metformin
Observational model: Cohort
Time perspective: Prospective
Sampling method: Probability Sample
Study population: 
        Children and young adults ages 8 to 25 years with type 2 diabetes will be studied in a
        cross-sectional and longitudinal manner.
      
Keywords: Type 2 Diabetes; Obesity; Insulin; Metformin; Natural History; Overweight