Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance
Metabolic Effect of Metformin in Obese Insulin Resistant Adolescents With Normal Glucose Tolerance
The primary objective of this randomized, parallel group, double-blind, placebo-controlled study is to determine whether treatment with metformin enhances insulin sensitivity in a group of ethnically diverse obese insulin-resistant adolescents with normal glucose tolerance.
First Visit
Patients who agree to participate in this research study, will have an initial screening where the subject will be asked about his/her health, a sample of blood will be drawn, the subject will be examined, and an oral glucose tolerance (OGTT) test will be done.
If the subject meets all the requirements to be in the study and has a normal glucose tolerance test, he/she will be randomized to either the intensely (Euglycemic hyperinsulinemic clamp) or standard studied group and have the following six or seven tests performed: DEXA scan and Tanita, exercise step test, PAT test, MRI (Abdominal scan), MRS (leg scan), and Euglycemic hyperinsulinemic clamp (intensely studied group only). All of the tests are described below. Females will have a urine pregnancy test before each of these tests. If positive, the subject will not be allowed to participate/continue with the study.
This infusion will not affect the subject's blood sugar in a harmful manner. It will allow us to follow the release of glucose from the liver and glycerol from fat tissue.
The subject's blood sugar will be checked closely during the study by taking blood samples from the second I.V. Readings of the blood sugar on each sample will be made at the bedside. If the blood sugar starts to fall, it can be fixed right away. At the end of another three hours, the infusion will be stopped and the subject will eat a meal that will be provided for him/her. The infusion of glucose will be reduced while the subject is eating until the subject's blood sugar is stable. This test takes about 6 hours. The total amount of blood drawn during this test will be less than 8 tablespoons or about half a cup.
Indirect calorimetry is a way to measure how much sugar and fat a person is burning when we give insulin. Testing how much fat and sugar a subject burns is an important part of the insulin, glucose, and glycerol infusion study. Therefore we will ask the subject to wear a plastic hood (like an astronaut space helmet) before starting the infusion of insulin and at two other times during the study.
Taking Metformin or Placebo
Once the subject has completed the six (standard studied group) or seven (intensely studied group only) tests described above, as well as two urine tests for protein, he/she will be randomized to either:
The subject will begin by taking one pill (either Metformin or placebo) every day, just before supper. The dose will be slowly increased as follows:
Week 1: Before breakfast = 0 and Before supper = 1 (500mg); Week 2: Before breakfast = 1 (500mg) and Before supper = 1 (500mg); Week 3-14: Before breakfast = 1 (500mg) and Before supper = 2 (500mg)
The subject will be taking the pills for 3 1/2 months, during which time we will ask that he/she keep a diary of any complaints, problems, or symptoms. Neither the subject, the subject's doctor, nor any of the members of the research team will find out which pill the subject was taking until the end of the study.
Monthly Follow-up
Subjects will be asked to come back every month for a physical exam. We will measure their height, weight, and blood pressure each time. A urine pregnancy test will be done on all female participants at every visit. At the subject's first follow up visit we will draw a small amount of blood and run tests to make sure the subject is healthy. We will ask the subject and his/her parent about any symptoms that the subject has had, any pills that he/she might have missed taking, and the use of other medications. We will measure the subject's vitamin B12 level on his/her third follow up visit.
End of Study
About three months after the subject begins taking the Metformin or placebo pills, he/she will repeat the tests described above (oral glucose tolerance test, DEXA and Tanita, exercise step test, PAT test, MRI, and MRS). In the sub-group of participants who had the glucose, insulin, and glycerol infusion test, this will also be repeated at the end of the study.
Open Label Phase (Taking Metformin)
After the tests described above are completed, all participants (even if they had been assigned a placebo pill) will be given the choice of taking Metformin for the next six months. If the subject does choose to continue, we will continue to monitor him/her monthly, as described in the section above on monthly follow-up. At the end of the additional six months, we will repeat all the tests that the subject had at the beginning of the study. For the intensely studied group, this includes the insulin, glucose and glycerol infusion.
Inclusion Criteria:
Exclusion Criteria: