Obesity, Type 1 Diabetes
Conditions
Keywords
Diabetes Mellitus, T1DM
Brief summary
The investigators hypothesize that PET scans will be able to differentiate between normal, reduced or increased BCM in human subjects. Subjects with normal BCM will be recruited from among normal weight nondiabetic people with plasma insulin levels within the normal range. Subjects with predicted reduced BCM will be recruited from among patients with T1DM who have with low or not measurable insulin levels. If results from the nondiabetic subjects and the subjects with T1DM are found to differ significantly, subjects with increased BCM will be recruited from among patients with hyperinsulinemia including those with obesity and the metabolic syndrome. PET scan measurements of the pancreas will be obtained and compared in people predicted, on the basis of biochemical testing, to have normal or reduced, or increased BCM.
Detailed description
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.
Interventions
None listed
Sponsors
Columbia University
Study design
Observational model
OTHER
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
Potential participants must meet all of the following inclusion criteria: 1. Informed consent obtained from participants 2. Age 18-45 years 3. 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 4. 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 5. 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. 6. Able to tolerate PET imaging: not claustrophobic, able to lie supine for 1.5 hours 7. 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 8. Adequate collateral circulation in the wrist as assessed by Allen Test.
Exclusion criteria
Potential participants must not have any of the following
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pancreas [11C] DTBZ binding | Once |
Countries
United States
Outcome results
None listed