Exenatide (Byetta) Vs Pramlintide (Symlin): Role in Post-prandial Hyperglycemia

After signing an informed consent, prior to study enrollment, a screening evaluation will be performed in the Clinical Research Center (CRC).

The evaluation will consist of: a medical history, a physical examination with vital signs, Tanner staging, and a waist circumference. The following laboratory tests will be done: CBC, HbA1c, creatinine,Liver function tests, amylase, lipid profile, lipase, urine for pregnancy test (when appropriate) and microalbumin. A urine pregnancy test will be done at each study visit in menstruating females. Also an anti-GAD,IA12, and anti-insulin antibody test will be done, if they were not previously done or if records are not available. Each subject will have a continuous glucose monitoring sensor (CGMS) inserted and will need to wear it for 3 days (72 hours). A person,trained to insert the subcutaneous sensor, will insert the sensor. The sensor is inserted subcutaneously with an injector device. This site insertion is very similar to an insulin pump site insertion. A recorder is attached to the sensor and records blood glucose data for 72 hours. The subject will need to test their blood glucose at least 4 times a day while wearing the sensor. The subject will be asked to keep a log on diet, insulin and exercise while wearing the CGMS. At the end of the 3 day sensing period, the subject will remove the sensor and place the recorder on a charger. The sensor will be brought back by the subject to Visit #1. A Mixed Meal Tolerance Test will be performed at this visit (as described below): Preparation for Mixed Meal Tolerance Test (MMTT)

1. The test will be performed in the morning (between 7 and 10 AM)

2. Test will be conducted only if fasting value by capillary blood glucose meter is between 70-200 mg/dl (3.9-11.1mMol). If the blood glucose prior to start of MMTT is greater than 350 mg/dl, then urine ketones will be measured. If a subject's blood glucose is less than 70 mg/dl before the Mixed Meal Tolerance Test, they will receive 5-10 grams of dextrose 50% by IV. If a subject develops hyperglycemia after the MMTT (which is expected), they will receive a supplemental bolus of fast acting insulin based on their usual insulin sensitivity factor. The subject will be instructed by the study staff on the amount needed. The subject will administer the bolus by themselves

3. Participants on injections will not withhold taking long acting insulin on the morning of the test. Participants can take very short acting insulin (e.g. Humalog or Novolog) up to 2 hours before the test if necessary and then that will be withheld during the test.

4. Participants on insulin pumps will continue with the normal basal rate. Participants can take very short acting insulin (e.g. Humalog or NovoLog) up to two hours before the test if necessary.

5. The participant will be fasting for at least 8 hours and will have had no food or drink (with the exception of water).

6. Local anesthetics may be used as needed to start the I.V. line. Conducting the Mixed Meal Tolerance Test (MMTT)

7. Baseline blood samples will be drawn at -30 minutes; -10 minutes and 0 minutes (immediately before the participant starts drinking the liquid meal) Baseline samples will include glucose, insulin, C-peptide, amylin, GLP-1, glucagon and active ghrelin.

8. The participant will have a standardized liquid meal: Boost HP 6 ml/kg, with a maximum of 360 ml, to be ingested within 5 minutes.