Determination of lnsulin-Stimulated whole body Glucose Uptake by PET-CT measurements

During the development of chronic metabolic disorders, such as obesity, fatty liver disease and type 2 diabetes, whole body insulin resistance develops. The gold standard to quantify this insensitivity to the hormone insulin is the hyperinsulinemic euglycemic clamp technique. However, during this procedure, the information on glucose uptake in the various tissues is very limited. Using dynamic Positron Emission Tomography (PET) with fluorinated glucose tracer (FDG), the uptake of glucose can actually be visualized and quantified in all the different tissues of the body. Therefore, when performed in the insulin-stimulated state, this method yields information of insulin-stimulated glucose uptake in any given tissue. During the development of a fatty liver, it is assumed that especially the liver becomes insulin resistant.

Indeed, the glucose output (determined during hyperinsulinemic euglycemic clamp) is less suppressed by insulin in a population with NAFL. However, it is yet unclear whether also the insulin-stimulated glucose uptake is affected in NAFL. This can be investigated by dynamic FDG-PET imaging. Therefore, the present proposal has applied this method for the investigation of NAFL. We first set up a dynamic measurement protocol with a minimal FDG dose in order to be able to investigate tissue-specific insulin-stimulated glucose uptake in a group of volunteers with a wide range of liver fat content (n=15, with equally distributed numbers of participants in the group <5%, 5-15% and >15% of liver fat content). This yielded detailed insight in the organ-specific insulin stimulated glucose uptake and showed that insulin stimulated glucose uptake in the liver is disturbed with increasing liver fat content. This illustrates that hepatic insulin resistance also extends to glucose uptake and not only suppression of glucose output in NAFL.