Multi-Tracer PET Quantitation of Skeletal Muscle Insulin Resistance in Type 2 Diabetes Mellitus
The purpose of this research is to use a recently developed triple-tracer positron emission tomography (PET) method to study skeletal muscle insulin resistance. Insulin is the hormone made by your body to control the blood sugar level. "Resistance' to insulin could cause poor blood glucose control (blood sugar levels that are higher than normal). We want to use this new method to image (look at) the following three things: 1) how insulin affects blood flow in skeletal muscle 2) how insulin affects glucose (sugar) transport (movement) into muscle, and 3) how insulin affects glucose metabolism (breakdown) in skeletal muscle of healthy individuals.
PET imaging is a relatively non-invasive way to obtain a "metabolic picture" of body organs and has been used successfully to study brain, heart and more recently skeletal muscle. In this research study, we will use PET, with three radioactive tracers (markers), to study skeletal muscle glucose transport in individuals with type 2 diabetes mellitus (type 2 DM) and in non-diabetic individuals who are either normal weight or overweight/obese
|Study Design:||Time Perspective: Prospective|
|Official Title:||Three-Tracer PET Quantitation of Insulin Action in Muscle|
- Compare triple tracer PET imaging of skeletal muscle in lean, obese and T2DM
- Mathematical modeling of PET data.
|Study Start Date:||January 2004|
|Estimated Study Completion Date:||December 2006|
The goal of this proposal is to use a recently developed triple-tracer positron emission tomography (PET) method to study skeletal muscle insulin resistance (IR) in research volunteers with type 2 diabetes mellitus (type 2 DM) and in comparison to age and gender-matched, normal weight non-diabetic volunteers, and in comparison to age, gender, and weight-matched overweight or obese non-diabetic volunteers. We will use the three tracers to obtain data on the respective insulin actions upon tissue perfusion, glucose transport and glucose phosphorylation in order to test the hypothesis that insulin resistance (IR) in type 2 DM is caused by an aggregation of impairments at these steps, thus challenging the prevalent concept that IR derives from a solitary impairment in trans-membrane transport.
Proximal steps of glucose transport and phosphorylation are considered to contribute strongly to the pathogenesis of IR in obesity and type 2 DM (1-5). These scientific considerations might have potential therapeutic implications. The overall goal of this project is to provide clarity in separating the respective roles of these proximal steps of glucose metabolism. Glucose transport will be assessed using 11C-3-O-methyl glucose (half-life ~ 20 min; also referred to as 3-0-MG), an analog that is transported but not phosphorylated. 18F-2-deoxy-2-fluoro-glucose (half-life ~ 109 min; also referred to as FDG), will be used to assess glucose transport and glucose phosphorylation. The third tracer that will be used, 15O-H2O, will provide information on tissue perfusion. The challenge with the use of FDG to study insulin action in muscle has been to derive data on two biochemical steps from the tissue activity pattern of a single tracer; this has placed a higher reliance upon the modeling of the data. However, in this project, because of the use of three tracers and the differences in the metabolism of the two glucose analogs, we will be able to address with clear resolution the respective roles of transport and phosphorylation in the pathogenesis of IR in obesity and type 2 DM.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00222781
|United States, Pennsylvania|
|University of Pittsburgh|
|Pittsburgh, Pennsylvania, United States, 15213|
|Principal Investigator:||David E Kelley, MD||University of Pittsburgh|