Background: Type-2 diabetes mellitus (T2DM) can affect the brain leading to cognitive deficits and impaired neuroplastic mechanisms. The objective of this study was to assess glutamate metabolism and its relationship with cortical plasticity in older adults with impaired glucose intolerance and insulin resistance. Methods: Forty adults (50-87 years) participated, including 17 with T2DM, 14 with pre-diabetes (PreDM), and 9 controls. All subjects underwent magnetic resonance spectroscopy to quantify glutamate and other key metabolites within a 2cm3 region around the hand knob of the left primary motor cortex. Thirty-six participants underwent a separate transcranial magnetic stimulation (TMS) assessment of cortical plasticity, defined as the change in the average amplitude of motor evoked potentials (MEPs) following intermittent theta-burst TMS (iTBS). Group differences in cortical plasticity and metabolism were assessed with one-way analyses of variance (ANOVAs) and related to each other by linear regression. Findings: The ANOVAs yielded significant group variance in relative concentrations of glutamine (p=.028), glucose (p=.008), total cholines (p=.048), and the glutamine/glutamate ratio (p=.024). Cortical plasticity was reduced in both T2DM and PreDM (p's<.05). As a possible mechanism of action, there was a significant association in T2DM between glutamate concentration and facilitation of MEPs (r=.56, p=.030). Interpretation: The current findings indicate impaired mechanisms of plasticity may be present at the earliest stages of glucose intolerance and that in T2DM, cortical plasticity may depend in part on the availability of free glutamate at the synapse. Funding Statement: This study was primarily funded by the National Institutes of Health (NIH R21 NS082870). A.P.-L. was also supported in part by the Sidney R. Baer Jr. Foundation, the NIH (R01HD069776, R01NS073601, R21 MH099196, R21 NS085491, R21 HD07616), and Harvard Catalyst | The Harvard Clinical and Translational Science Center (NCRR and the NCATS NIH, UL1 RR025758). The content is solely the responsibility of the authors and does not necessarily represent the official views of Harvard Catalyst, Harvard University and its affiliated academic health care centers, the National Institutes of Health, or the Sidney R. Baer Jr. Foundation. Declaration of Interests: A.P.-L. serves on the scientific advisory boards for Nexstim, Neuronix, Starlab Neuroscience, Neuroelectrics, Cognito, Constant Therapy, and Neosync; and is listed as an inventor on several issued and pending patents on the real-time integration of transcranial magnetic stimulation with electroencephalography and magnetic resonance imaging. The authors declare no competing interests. Ethics Approval Statement: The manuscript details research conducted on human participants. All provided written informed consent consistent with the Declaration of Helsinki. All forms and procedures were approved by the Institutional Review Board at Beth Israel Deaconess Medical Center, where the research took place.