PET Scan Imaging of Beta Cell Mass

An important determinant of progression to diabetes is beta cell mass (BCM). Measurement of plasma insulin has been used as a surrogate marker but insulin levels often do not correlate well with beta cell mass and development of means to assess BCM would provide an important endpoint. For example, high-risk individuals could be monitored prior to onset of diabetes or patients could be monitored prospectively to determine the progression of their disease and response to therapy.

Both Type 1 diabetes mellitus (T1DM) and Type 2 diabetes mellitus (T2DM) develop when there is impaired insulin production. The amount of insulin that can be produced, the amount of insulin producing beta cells in the pancreas and level of insulin and glucose in the blood are, however, imperfectly correlated. The development of a reliable method to noninvasively quantitate the beta cell mass (BCM) would be of great benefit by providing an important endpoint for the development of new treatments of T1DM and T2DM. The investigators have previously identified a specific marker on islet cells called vesicular monoamine transporter 2 (VMAT2) that they now propose to use in positron emission tomography (PET) scanning to determine islet cell mass. This radioligand, [11C] Dihydrotetrabenazine (DTBZ), has been used previously in human subjects in clinical trials evaluating PET scanning of the brain in patients with bipolar illness and schizophrenia compared to healthy control subjects.

Inclusion criteria

Potential participants must meet all of the following inclusion criteria:

• Informed consent obtained from participants
• Age 18-45 years
• Healthy non-diabetic subjects will have normal fasting blood sugar (<100 mg/dl), body mass index (BMI) 18.5-24.9, no history of type 2 diabetes in first degree relative
• Type 1 diabetes defined by: American Diabetes Association (ADA) criteria or judgment of physician; diabetes onset younger than age 18, duration >5 - years, BMI 18.5-24.9. Insulin dose <0.8 units/kg/day. Fasting c-peptide < 0.1 ng/ml
• Obese hyper-insulinemic subjects will have BMI > 30 and fasting insulin>20 and c-peptide> 4.6 ng/ml and normal fasting blood sugar <100 mg/dl.
• Able to tolerate PET imaging: not claustrophobic, able to lie supine for 1.5 hours
• Normal liver and renal function tests including normal spot urine microalbumin /creatinine; normal CBC including hematocrit >31.8% in women, >36.7% in men, white blood cell (WBC) count >3.4 K/mm3 and platelet count >162 K/mm3
• Adequate collateral circulation in the wrist as assessed by Allen Test.

Exclusion criteria

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

• Previous or current treatment with drugs influencing beta cell function or insulin sensitivity (e.g. oral hypoglycemic agents, glucocorticoids); or with antipsychotic, antianxiety, or antidepressant medications (eg monoamine oxidase (MAO) inhibitors, 5-hydroxytryptamine (5-HT) inhibitors, tricyclic antidepressants); or treatment with reserpine; or treatment with beta2receptor agonists (eg, terbutaline); or treatment with anticoagulant medication.
• History of movement disorder such as Parkinson's Disease or Huntington's Disease
• History of or psychiatric illness such as depression, bipolar disease, anxiety or schizophrenia.
• If a female of childbearing age, currently pregnant, breastfeeding or not using a form of birth control
• Previous or current use of cocaine, methamphetamine, ecstasy
• Current daily intake of caffeine >500 mg/day (>45 cups of coffee; >10 12oz cans of soda)
• Current history of cigarette smoking
• Consumption of more than 1 alcoholic drink per day
• Evidence of chronic infection
• History of malignancy
• Any prior participation in other research protocols within the past year that involve radiation, with the exception of plain radiography studies (i.e., chest xrays).
• Medical implant