Insulin Resistance Is Associated With Enhanced Brain Glucose Uptake During Euglycemic Hyperinsulinemia: A Large-Scale PET Cohort

Abstract

<b>Objective</b> Whereas insulin resistance is expressed as reduced glucose uptake in peripheral tissues, the relationship between insulin resistance and brain glucose metabolism remains controversial. Our aim was to examine the association of insulin resistance and brain glucose uptake (BGU) during a euglycemic hyperinsulinemic clamp in a large sample of subjects across a wide range of age and insulin sensitivity. <p><b>Research Design and Methods</b> [<sup>18</sup>F]-fluorodeoxyglucose positron emission tomography (PET) data from 194 subjects scanned under clamp conditions were compiled from a single-center cohort. BGU was quantified by the fractional uptake rate. We examined the association of age, sex, M value from the clamp, steady-state insulin and free fatty acids levels, C-reactive protein, HbA<sub>1c,</sub> and presence of type 2 diabetes with BGU using Bayesian hierarchical modeling. </p> <p><b>Results</b> Insulin sensitivity, indexed by the M value, was associated negatively with BGU in all brain regions, confirming that in insulin resistant subjects BGU is enhanced during euglycemic hyperinsulinemia. In addition, the presence of type 2 diabetes was associated with a further increase in BGU. On the contrary, age was negatively related to BGU. Steady-state insulin levels, C-reactive protein, free fatty acids, sex, and HbA<sub>1c</sub> were not associated with BGU.</p> <p><b>Conclusions </b>In this large cohort of subjects of either sex across a wide range of age and insulin sensitivity,<b> </b>insulin sensitivity is the best predictor of brain glucose uptake. <b></b></p>