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Diabetologia. 2009 Nov;52(11):2328-2336. doi: 10.1007/s00125-009-1484-7. Epub 2009 Aug 18.

Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes: the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial.

Author information

1
The George Institute for International Health, The University of Sydney, PO Box M201, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia.
2
Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
3
The George Institute for International Health, The University of Sydney, PO Box M201, Missenden Road, Camperdown, Sydney, NSW, 2050, Australia. szoungas@george.org.au.
4
Monash University, Melbourne, VIC, Australia. szoungas@george.org.au.
5
INSERM U708, Paris, France.
6
UPMC University of Paris, Paris, France.
7
Baker IDI Heart Research Institute, Melbourne, VIC, Australia.
8
Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, the Netherlands.
9
Centre Hospitalier de l'Université de Montreal and Université de Montreal, Montreal, QC, Canada.
10
University of Sheffield and Sheffield Teaching Hospitals National Health Service Foundation Trust, Sheffield, UK.
11
Chinese Hypertension League Institute, Beijing, China.
12
University of Milan-Bicocca and San Gerardo Hospital, Milan, Italy.
13
Chinese People's Liberation Army General Hospital, Beijing, China.
14
Imperial College and St Mary's Hospital, London, UK.
15
Mount Sinai School of Medicine, New York, NY, USA.

Abstract

AIMS/HYPOTHESIS:

The relationship between cognitive function, cardiovascular disease and premature death is not well established in patients with type 2 diabetes. We assessed the effects of cognitive function in 11,140 patients with type 2 diabetes who participated in the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial. Furthermore, we tested whether level of cognitive function altered the beneficial effects of the BP-lowering and glycaemic-control regimens in the trial.

METHODS:

Cognitive function was assessed using the Mini Mental State Examination at baseline, and defined by scores 28-30 ('normal', n = 8,689), 24-27 ('mild dysfunction', n = 2,231) and <24 ('severe dysfunction', n = 212). Risks of major cardiovascular events, death and hypoglycaemia and interactions with treatment were assessed using Cox proportional hazards analysis.

RESULTS:

Relative to normal function, both mild and severe cognitive dysfunction significantly increased the multiple-adjusted risks of major cardiovascular events (HR 1.27, 95% CI 1.11-1.46 and 1.42, 95% CI 1.01-1.99; both p < 0.05), cardiovascular death (1.41, 95% CI 1.16-1.71 and 1.56, 95% CI 0.99-2.46; both p <or= 0.05) and all-cause death (1.33, 95% CI 1.16-1.54 and 1.50, 95% CI 1.06-2.12; both p < 0.03). Severe, but not mild, cognitive dysfunction increased the risk of severe hypoglycaemia (HR 2.10, 95% CI 1.14-3.87; p = 0.018). There was no evidence of heterogeneity of treatment effects on cardiovascular outcomes in subgroups defined by cognitive function at baseline.

CONCLUSIONS/INTERPRETATION:

Cognitive dysfunction is an independent predictor of clinical outcomes in patients with type 2 diabetes, but does not modify the effects of BP lowering or glucose control on the risks of major cardiovascular events.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT00145925.

PMID:
19688336
DOI:
10.1007/s00125-009-1484-7
[Indexed for MEDLINE]

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