Dysregulation of Hypothalamic-Pituitary-Adrenal Axis Explain the Dynamic Association Between Glucose Fluctuation and Cognitive

Abstract

Objective—Type 2 diabetes mellitus is a risk factor for cognitive dysfunction. However, the underlying mechanism of cognitive decline in patients with type 2 diabetes mellitus is still elusive. Dysregulation of HPA axis is related to cognitive impairment. The present study aims to calculate explanation of the association between glucose fluctuation and cognitive function by HPA axis in type 2 diabetes mellitus patients. Methods—The mean amplitude of glycemic excursion (MAGE) was analyzed by a continuous glucose monitoring system (CGMS) for 3 days in 330 elderly type 2 diabetes mellitus patients. All the subjects received a set of neuropsychological test battery for cognitive assessment. The diurnal rhythm of cortisol was also analyzed. Linear multivariate regression analysis was performed to explore the relationship between glucose fluctuation, cortisol parameters and cognitive parameters. Results—MAGE was observed to be associated with diurnal cortisol fall but with neither cortisol awakening response (CAR) nor overall mean cortisol levels (t = –2.195, P = 0.030). Linear multivariate regression analysis displayed that MAGE and average diurnal cortisol fall were uniquely associated with some cognitive parameters, such as AVLT trial, FAS, and TMT (P < 0.05). Conclusion—Glucose fluctuation was strongly associated with cognitive impairment in elderly type 2 diabetes mellitus patients. Especially in executive function, attention and processing speed. Dysregulation of HPA axis was probably the cause of cognitive dysfunction in these patients.