Amygdalar activity predicts future incident diabetes independently of adiposity

Abstract While it is established that psychosocial stress increases the risk of developing diabetes mellitus (DM), two key knowledge gaps remain: 1) the neurobiological mechanisms that are involved in mediating that risk, and 2) the role, if any, that adiposity plays in that mechanism. We tested the hypotheses that: 1) metabolic activity in the amygdala (AmygA), a key center involved in the neurobiological response to stress, associates with subsequent DM risk, and 2) this association is independent of adiposity. AmygA and adipose tissue volumes were measured, and serial blood assessments for DM were obtained in 232 subjects who underwent combined 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG-PET/CT) imaging. Higher baseline AmygA predicted subsequent, new-onset DM, independently of adiposity and other DM risk factors. Furthermore, higher adiposity only increased DM risk in the presence of higher AmygA. In a separate cross-sectional cohort, higher AmygA associated with higher insulin resistance. Accordingly, the current study shows, for the first time, that activity in a stress-responsive neural region predicts the onset of DM. Further, we observed that this neurobiological activity acts independently of, but also synergistically with adiposity to increase DM risk. These findings suggest novel therapeutic targets to help manage and possibly prevent DM.