Neural, Hormonal, and Cognitive Correlates of Metabolic Dysfunction and Emotional Reactivity.

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