PET Imaging of Regional Variation in Insulin Sensitivity of Adipose Tissue in Humans
Condition: Diabetes; Obesity
Study type: Observational

Summary: 
      The purpose of this research study is to use a relatively new technology, called Positron
      Emission Tomography (PET), to study how insulin works on sugar in your body's fatty tissue.
      PET imaging is a way of obtaining a "metabolic image" of your internal organs. It does not
      involve surgery and is not a high risk process. It has been used successfully to study brain,
      heart and more recently, skeletal muscle. In this research study, we will use PET in
      combination with Magnetic Resonance Imaging (MRI), to study fatty tissues in healthy people
      who do not have diabetes. In the future, we plan to do similar PET/MRI studies in individuals
      with type 2 diabetes mellitus (T2DM) and in individuals who are likely to develop T2DM.

      Fat tissue might have a lot to do with developing type 2 diabetes. First, it is well
      recognized that excess fatty tissues, especially the kind in your belly, increases risk for
      the development of T2DM, as well as affecting other ways the body uses insulin. Second, fatty
      tissue is a classic target tissue for the action of insulin, which regulates the use of sugar
      by fat cells and also regulates the release of fatty acids from fatty tissues. Third, studies
      in mice that lack fatty tissue, indicate that severe insulin resistance (lack of a normal
      response to insulin) can result. Other types of studies have shown that fatty tissues make
      proteins that affect your body's insulin and your appetite in good and bad ways. Yet despite
      this importance, we still lack techniques for the study of fatty tissue metabolism in humans.
    

Detailed description: 
      The association of adiposity with insulin resistance (IR) is modulated by regional fat
      deposition. For example, visceral (intra-abdominal) adipose tissue (VAT) is generally
      regarded as more strongly correlated with IR, than subcutaneous adiposity of the thigh
      (ThiSAT) or abdomen (AbdSAT), even though these latter depots are larger than VAT. Perhaps
      these differences are due to regional variation in AT metabolism. A limitation of body
      composition methods is that these assess amount rather than metabolism of adipose tissue
      (AT). Our aim is to use positron emission tomography (PET) imaging with [F-18]
      fluorodeoxyglucose (FDG) for the in vivo investigation of AT metabolism and use this in
      conjunction with regional body composition imaging so that both the amount of AT and
      metabolism of AT can be determined. Hopefully, such an approach will give new insight as to
      how AT influences skeletal muscle and hepatic IR. The current project seeks to develop this
      approach, generating preliminary data to lay a foundation for subsequent projects.

      The first specific aim is conduct dose-responsive measurement of insulin-stimulated glucose
      uptake (i.e. insulin sensitivity) of AT in humans using PET imaging in healthy volunteers. We
      will examine the effects of insulin infusion rates at 0, 20, and 80 mU/min-m2 body surface
      area.

      The second specific aim is to assess regional variation in insulin-stimulated glucose uptake
      in AT, comparing VAT, AbdSAT and ThiSAT in volunteers without IR. We will test the hypothesis
      that insulin sensitivity (IS) follows the rank order of ThiSAT IS > AbdSAT IS > VAT IS.

      At any given body mass index, fat mass constitutes a higher percentage of body weight in
      women than men. The third specific aim is to assess potential gender-differences in AT
      metabolism, testing the hypothesis that AT IS is greater in women than men.
    

Time perspective: Prospective
Keywords: Adipose tissue; PET imaging