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.
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
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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 -