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J Clin Endocrinol Metab. 2007 Jul;92(7):2439-45. Epub 2007 Apr 10.

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

Author information

1
Department of Psychiatry, New York University School of Medicine, 550 First Avenue, New York, New York 10016, USA.

Abstract

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.

PMID:
17426095
DOI:
10.1210/jc.2006-2540
[Indexed for MEDLINE]

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