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Prediabetes and type 2 diabetes (i.e., hyperglycemia) are characterized by insulin resistance. These problems with energy metabolism may exacerbate emotional reactivity to negatively valenced stimuli and related phenomena such as predisposition toward negative affect, as well as cognitive deficits. Higher emotional reactivity is seen with hyperglycemia and insulin resistance. However, it is largely unknown how metabolic dysfunction correlates with related neural, hormonal, and cognitive outcomes.Among 331 adults from the Midlife in the United States study, eye-blink response (EBR) we cross sectionally examined to gauge reactivity to negative, positive, or neutrally valenced pictures from international affect picture system stimuli proximal to an acoustic startle probe. Increased EBR to negative stimuli was considered an index of stress reactivity. Frontal alpha asymmetry, a biomarker of negative affect predisposition, was determined using resting electroencephalography. Baseline urinary cortisol output was collected. Cognitive performance was gauged using the Brief Test of Adult Cognition by telephone. Fasting glucose and insulin characterized hyperglycemia or the homeostatic model assessment of insulin resistance.Higher homeostatic model assessment of insulin resistance corresponded to an increased startle response, measured by EBR magnitude, for negative versus positive stimuli (R2 = 0.218, F(1,457) = 5.48, p = .020, euglycemia: M(SD) = .092(.776), hyperglycemia: M(SD) = .120(.881)). Participants with hyperglycemia versus euglycemia showed greater right frontal alpha asymmetry (F(1,307) = 6.62, p = .011, euglycemia: M(SD) = .018(.167), hyperglycemia: M(SD) = −.029(.160)), and worse Brief Test of Adult Cognition by telephone arithmetic performance (F(1,284) = 4.25, p = .040, euglycemia: M(SD) = 2.390(1.526), hyperglycemia: M(SD) = 1.920(1.462)). Baseline urinary cortisol (log10 μg/12 hours) was also dysregulated in individuals with hyperglycemia (F(1,324) = 5.09, p = .025, euglycemia: M(SD) = 1.052 ± .332, hyperglycemia: M(SD) = .961 (.362)).These results suggest that dysmetabolism is associated with increased emotional reactivity, predisposition toward negative affect, and specific cognitive deficits.