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

B. E. De Galan, S. Zoungas, J. Chalmers, C. Anderson, C. Dufouil, A. Pillai, M. Cooper, D. E. Grobbee, M. Hackett, P. Hamet, S. R. Heller, L. Lisheng, S. MacMahon, G. Mancia, B. Neal, C. Y. Pan, A. Patel, N. Poulter, F. Travert, M. Woodward

Research output: Contribution to journalArticle

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≤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.

Original languageEnglish (US)
Pages (from-to)2328-2336
Number of pages9
JournalDiabetologia
Volume52
Issue number11
DOIs
StatePublished - Nov 2009

Keywords

  • Blood pressure control
  • Cardiovascular disease risk
  • Cognitive function
  • Glucose control
  • Hypoglycaemia
  • MMSE
  • Mortality
  • Type 2 diabetes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    De Galan, B. E., Zoungas, S., Chalmers, J., Anderson, C., Dufouil, C., Pillai, A., Cooper, M., Grobbee, D. E., Hackett, M., Hamet, P., Heller, S. R., Lisheng, L., MacMahon, S., Mancia, G., Neal, B., Pan, C. Y., Patel, A., Poulter, N., Travert, F., & Woodward, M. (2009). 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. Diabetologia, 52(11), 2328-2336. https://doi.org/10.1007/s00125-009-1484-7