Hypothalamic-pituitary-adrenal axis dysregulation and memory impairments in type 2 diabetes.

CONTEXT

There is evidence of both hypothalamic-pituitary-adrenocortical (HPA) axis and cognitive dysfunction in type 2 diabetes mellitus (T2DM). However, the exact nature and the associations between these abnormalities remain unclear.

OBJECTIVES

The aim of the study was to characterize the nature of the HPA dysregulation in T2DM and ascertain whether impaired cognition in T2DM could be attributed to these abnormalities.

DESIGN

A cross-sectional study was performed, contrasting matched groups on HPA axis function and cognition by using the combined dexamethasone (DEX)/CRH test and a neuropsychological battery assessing declarative and working memory, attention, and executive function.

SETTING

The study was conducted in a research clinic in an academic medical center.

PARTICIPANTS

Participants were volunteers functioning in the cognitively normal range. We studied 30 middle-aged individuals with T2DM, on average 7.5 yr since diabetes diagnosis, and 30 age-, gender-, and education-matched controls.

MAIN OUTCOME MEASURES

Basal cortisol levels, cortisol levels during the DEX/CRH test, and performance on neuropsychological tests were measured.

RESULTS

Individuals with T2DM had elevated basal plasma cortisol levels, higher levels after DEX suppression, and a larger response to CRH (all P <or= 0.005). Among individuals with T2DM, cortisol levels during the DEX/CRH test were positively associated with glycosylated hemoglobin (P = 0.05), independent of age, body mass index, hypertension, and dyslipidemia. Diabetic subjects showed cognitive impairments restricted to declarative memory. Across all subjects, declarative memory was inversely associated with cortisol levels; however, these associations were subsumed by glycemic control (glycosylated hemoglobin).

CONCLUSIONS

HPA hyperactivity and declarative memory deficits are present in T2DM. Both alterations may reflect the negative impact of poor glycemic control on the hippocampal formation.