TY - JOUR
T1 - Cognitive function and risks of cardiovascular disease and hypoglycaemia in patients with type 2 diabetes
T2 - The action in diabetes and vascular disease: Preterax and diamicron modified release controlled evaluation (ADVANCE) trial
AU - De Galan, B. E.
AU - Zoungas, S.
AU - Chalmers, J.
AU - Anderson, C.
AU - Dufouil, C.
AU - Pillai, A.
AU - Cooper, M.
AU - Grobbee, D. E.
AU - Hackett, M.
AU - Hamet, P.
AU - Heller, S. R.
AU - Lisheng, L.
AU - MacMahon, S.
AU - Mancia, G.
AU - Neal, B.
AU - Pan, C. Y.
AU - Patel, A.
AU - Poulter, N.
AU - Travert, F.
AU - Woodward, M.
N1 - Funding Information:
Acknowledgements ADVANCE was funded by grants from Servier and the National Health and Medical Research Council of Australia. The sponsors had no role in the design of the study, data collection, data analysis, data interpretation and the writing of the manuscript. Study data were not made available to the sponsors. The Management Committee, whose membership did not include any sponsor representatives, had final responsibility for the decision to submit for publication. The first four authors had full access to the data of the study and take responsibility for the accuracy of the analysis.
Funding Information:
Trial registration: ClinicalTrials.gov NCT00145925 Funding: Supported by grants from Servier and from the National Health and Medical Research Council of Australia.
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2009/11
Y1 - 2009/11
N2 - 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≤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 Funding:: Supported by grants from Servier and from the National Health and Medical Research Council of Australia.
AB - 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≤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 Funding:: Supported by grants from Servier and from the National Health and Medical Research Council of Australia.
KW - Blood pressure control
KW - Cardiovascular disease risk
KW - Cognitive function
KW - Glucose control
KW - Hypoglycaemia
KW - MMSE
KW - Mortality
KW - Type 2 diabetes
UR - http://www.scopus.com/inward/record.url?scp=70349850941&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=70349850941&partnerID=8YFLogxK
U2 - 10.1007/s00125-009-1484-7
DO - 10.1007/s00125-009-1484-7
M3 - Article
C2 - 19688336
AN - SCOPUS:70349850941
VL - 52
SP - 2328
EP - 2336
JO - Diabetologia
JF - Diabetologia
SN - 0012-186X
IS - 11
ER -