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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A. Healthy Controls | subjects w/ predicted normal BCM (healthy, normalweight, nondiabetic individuals who have stimulated insulin and cpeptide levels within the normal range); | ||
| B. Longstanding T1D | subjects with predicted reduced beta cell mass (subjects with established T1DM who have low or not measurable stimulated insulin and c peptide levels); | ||
| C. Obese Subjects | subjects with predicted increased beta cell mass (euglycemic obese subjects with fasting hyperinsulinemia). |
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| Measure | Description | Time Frame |
|---|---|---|
| Pancreas [11C] DTBZ binding | Once |
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Inclusion Criteria:
Potential participants must meet all of the following inclusion criteria:
Exclusion Criteria:
Potential participants must not have any of the following exclusion criteria:
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Potential subjects with diabetes will be recruited from among the patients cared for at the Naomi Berrie Diabetes Center. Nondiabetic subjects will either be referred by their physicians or by word of mouth. Primary care physicians will be made aware of the study by fliers.
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| Name | Affiliation | Role |
|---|---|---|
| PAUL E HARRIS, Ph.D. | Columbia University | Study Director |
| Robin S Goland, M.D. | Columbia University | Principal Investigator |
| Ronald Van Heertum, M.D. | Columbia University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Naomi Berrie Diabetes Cener | New York | New York | 10032 | United States | ||
| Kreitchman PET Center Columbia University Medical Center |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 16710474 | Background | Souza F, Simpson N, Raffo A, Saxena C, Maffei A, Hardy M, Kilbourn M, Goland R, Leibel R, Mann JJ, Van Heertum R, Harris PE. Longitudinal noninvasive PET-based beta cell mass estimates in a spontaneous diabetes rat model. J Clin Invest. 2006 Jun;116(6):1506-13. doi: 10.1172/JCI27645. Epub 2006 May 18. | |
| 17045165 | Background |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| D009765 | Obesity |
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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Blood
| New York |
| New York |
| 19932 |
| United States |
| Simpson NR, Souza F, Witkowski P, Maffei A, Raffo A, Herron A, Kilbourn M, Jurewicz A, Herold K, Liu E, Hardy MA, Van Heertum R, Harris PE. Visualizing pancreatic beta-cell mass with [11C]DTBZ. Nucl Med Biol. 2006 Oct;33(7):855-64. doi: 10.1016/j.nucmedbio.2006.07.002. |
| 18060547 | Background | Murthy R, Harris P, Simpson N, Van Heertum R, Leibel R, Mann JJ, Parsey R. Whole body [11C]-dihydrotetrabenazine imaging of baboons: biodistribution and human radiation dosimetry estimates. Eur J Nucl Med Mol Imaging. 2008 Apr;35(4):790-7. doi: 10.1007/s00259-007-0648-2. Epub 2007 Dec 4. |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D001835 | Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |