Assessment of Beta Cell Mass by PET Scans With [11C] Dihydrotetrabenazine (DTBZ) in Longstanding Type 1 Diabetes.
Condition: Type 1 Diabetes
MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1
Study type: Observational

Summary: 
      We hypothesize that quantitative measurements of the beta cell mass within the endocrine
      pancreas can be obtained by PET via targeting of vesicular monoamine type 2 transporters with
      the radioligand [11C]DTBZ. and that there will be significant differences in [11C]DTBZ uptake
      in the anatomical space of the pancreas between normal individuals and those with BCM
      predicted to be greater or less than normal based on the measurement of insulin secretion.
    

Detailed description: 
      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 with BCM and a "gold standard of
      measurement" to obtain this type of information would be of great value. The aim of the
      proposed study is to evaluate an islet imaging technique using PET scanning that will be able
      to be used for directly measuring 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 be sometimes be identified before the disease
      develops by measuring autoantibodies to beta cells, however this test is neither very
      sensitive or specific. In contrast, type 2 diabetes (T2DM) occurs in a setting of insulin
      resistance leading to hyperinsulinemia. In people at high risk for T2DM, beta cell mass
      increases to meet the demand for more insulin. The individual becomes diabetic when the BCM
      and insulin production can no longer compensate for the increased need for insulin, and blood
      glucose begins to rise. Loss of BCM may then occur as T2DM advances. People at high risk for
      T2DM include first degree relatives of patients with T2DM and those with obesity, insulin
      resistance and the metabolic syndrome. 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 is only 1-2% of the organ. Accurate assessment of BCM in
      human diabetes is limited to autopsy studies, which usually suffer from inadequate clinical
      information; thus, the development of noninvasive means of BCM measurement could be
      important, not only in intervention therapy of T1DM and T2DM, islet regeneration/stem cell
      therapy and islet transplantation.

      Until recently, islet cell mass visualization has not been clinically feasible. We have
      previously identified a specific marker on pancreatic beta cells called vesicular monoamine
      transporter type 2 (VMAT2). In preclinical studies, we have shown that imaging beta cell mass
      with PET scanning using this radioligand is feasible in rats and in dosimetry studies
      conducted in baboons. This radioligand, [11C]DTBZ, has been used previously in human subjects
      in clinical trials evaluating P.E.T scanning of the brain in patients with bipolar illness
      and schizophrenia compared to healthy control subjects. In the current protocol, we propose
      to use a radioligand, [11C]DTBZ, that binds to VMAT2 in positron emission tomography (PET)
      scanning to assess whether PET can measure beta cell mass in human subjects.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Type 1 diabetes
      
Keywords: Type 1 diabetes