Project summary/abstract The prevalence of type 2 diabetes mellitus continues to rise worldwide and despite different treatment options, many patients fail to achieve glycemic target, which leads to increased morbidity and mortality. Chronic exposure to hyperglycemia has been shown in both animal and human studies to decrease glucose transport into the brain, presumably through down-regulation of GLUT1 at the blood brain barrier, which has been postulated to be a protective adaptation of the central nervous system against the harmful consequences of hyperglycemia. However, GLUT1 down regulation may lead to reduced brain glucose metabolism leading to neuronal damage, neurodegeneration and cognitive decline. Whether these changes in cerebral glucose transport seen in patients with poorly controlled diabetes can be reversed is unknown. The main goal of this study is to determine whether improvement of glucose control in poorly controlled T2DM patient will restore brain glucose transport kinetics and rigorously assess which factors (i.e. duration DM and glycemic control) contribute to the observed improvements by using classic metabolic studies as well as state-of-the-art brain nuclear magnetic resonance spectroscopy (MRS) techniques. The findings obtained from this study will help elucidate if intensive diabetes therapy may be associated with reduced brain dysfunction from hyperglycemia.