Type 1 diabetes mellitus (T1DM) develops when there is impaired insulin production due to loss of insulin producing cells (beta cells). The amount of insulin that can be produced is imperfectly correlated with beta cell mass (BCM). The development of a reliable method to noninvasively quantify the total amount of insulin producing beta cells would be of great benefit by providing an important endpoint for the development of new treatments of diabetes. The investigators have previously identified a specific marker on islet cells called vesicular monoamine transporter 2 (VMAT2) that the investigators now propose to use in positron emission tomography (PET) scanning to determine islet beta cell mass. The PET radiopharmaceutical 18 F-fluoropropyl(FP)-dihydrotetrabenazine(DTBZ) has been used previously in human subjects without adverse effects. It has shown promise in differentiating type 1 diabetes and non-diabetes. The investigators now hypothesize that repeat PET scans will be reproducible in the same subject. Subjects with normal BCM will be recruited from among normal weight non-diabetic people with plasma insulin levels within the normal range. Subjects with predicted reduced BCM will be recruited from among patients with T1DM who have low or non-measurable insulin levels. Two PET scan measurements will be taken in each subject and the amount of VMAT2 in the pancreas will be and compared for reproducible findings. Biochemical testing will also be performed and compared to PET scans as a potential indirect marker of beta cell mass.

Diabetes results when the insulin secretory capacity of the beta cell population is lost or severely compromised.Plasma insulin levels have been used as a surrogate marker of beta cell mass (BCM) but insulin levels often do not correlate well. A "gold standard of measurement" to obtain BCM would be of great value. The aim of the proposed study is to evaluate an islet imaging technique using PET scanning to directly measure BCM and thus provide valuable information for monitoring disease progress and response to therapy in people with diabetes and in people at high risk for diabetes. Type 1 diabetes (T1DM) occurs when the beta cells are selectively destroyed by a T cell mediated autoimmune process. People at high risk for developing T1DM, such as first degree relatives of patients with T1DM, can sometimes be identified before the disease develops by measuring autoantibodies to beta cells, however this test is neither sensitive nor specific. Little is known about the natural history of BCM, turnover and cell lifetime, or the course of inflammation in diabetes. This is principally because the pancreas is a highly heterogeneous organ that is difficult to biopsy without significant complications, and BCM only comprises 1 to 2% of the total volume. Accurate assessment of BCM in human diabetes is limited to autopsy studies, which usually suffer from inadequate clinical information; thus, the development of non-invasive means of BCM measurement could be important for interventional therapies of T1DM, islet regeneration/stem cell therapy and islet transplantation.

Inclusion Criteria:

• Patients with type 1 diabetes may be enrolled if they meet all of the following criteria:

  1. Are males or females between 18 and 70 years of age, inclusive
  2. Have a diagnosis of type 1 diabetes mellitus as defined by the American Diabetes Association (ADA) criteria or by diagnosed as per their endocrinologist; duration >5 years; Insulin dose requirements <0.8 units/kg/day
  3. HbA1c level between 5% and 8.5%
  4. Have fasting C-Peptide < 0.1 ng/ml
  5. Have a body mass index (BMI) between 18 and 32 kg/m2
  6. Able to tolerate PET imaging
  7. In the judgment of the physician, are capable of fasting 4 to 6 hours prior to screening and Day 1 imaging procedures
  8. Give informed consent

Healthy volunteers may be enrolled if they meeting all of the following criteria:

1. Are males or females between 18 and 70 years of age, inclusive
2. Have no history of type 1 or type 2 diabetes in a first degree relative
3. Fasting blood glucose less than 100 mg/dL
4. HbA1c level less than 6%
5. Normal Mixed Meal Tolerance test at screening visit
6. BMI between 18 and 32 kg/m2
7. Able to tolerate PET imaging
8. In the judgment of the physician, are capable of fasting 4 to 6 hours prior to screening and Day 1 imaging procedures, and
9. Give informed consent

Exclusion Criteria:

• Potential participants must not have any of the following exclusion criteria:

  1. Clinically significant renal dysfunction

  2. Clinically significant liver dysfunction as determined by history, physical examination, and standard liver function testing at screening (aspartate aminotransferase (AST), alanine aminotransferase (ALT), Total/Direct Bilirubin, Alkaline Phosphatase)

  3. Coagulopathy

  4. Use medications known to affect dopaminergic function, including monoamine oxidase (MAO) inhibitors, tetrabenazine, or levodopa

  5. Recent (within 3 months) or current treatment with drugs influencing beta cell function or insulin sensitivity (e.g. glucocorticoids, reserpine) medications known to affect dopaminergic function, including MAO inhibitors, tetrabenazine, or levodopa

  6. Have polycystic ovarian syndrome

  7. History of movement disorder such as Parkinson's Disease, Huntington's Disease

  8. Clinically significant psychiatric disease or history of psychiatric illness such as depression, bipolar disease, anxiety or schizophrenia

  9. Current use (within past year) of cocaine, methamphetamine, and/or ecstasy (3,4methylenedioxymethamphetamine (MDMA))

  10. Have a recent history of alcohol or substance abuse or dependence

  11. Clinically significant cardiovascular disease or clinically significant abnormalities on screening electrocardiogram (ECG) (including but not limited to QT-interval time corrected > 450 msec)

  12. Clinically significant pulmonary, renal or hepatic impairment, or cancer

  13. Have clinically significant infectious disease, including acquired immune deficiency syndrome (AIDS) or human immunodeficiency virus (HIV) infection or previous positive test for hepatitis B, hepatitis C, or HIV.

  14. Are women of childbearing potential not refraining from sexual activity or not using adequate contraception.

      Women must not be pregnant (negative serum human chorionic gonadotropin (hCG) at the time of screen) or breastfeeding at screening, and must agree to take appropriate steps not to become pregnant during for 30 days following the clinical trial

  15. Require medications with a narrow therapeutic window (e.g., warfarin), are receiving any investigational medications, or have participated in a trial with investigational medications within the last 30 days

  16. Weigh more than the manufacturer recommended limit for the PET/computed tomography (CT) camera being used

  17. Any prior participation in other research protocols within the past month that involved radiation, with the exception of plain radiography studies (i.e., chest x-rays); And

  18. Have received a diagnostic or therapeutic radiopharmaceutical within the past week

Throughout study period, up to 2 months