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History of lower-limb complications and risk of cancer death in people with type 2 diabetes

  • Mohammedi, Kamel1, 2, 3
  • Harrap, Stephen4
  • Mancia, Giuseppe5
  • Marre, Michel6, 7, 8
  • Poulter, Neil9
  • Chalmers, John10, 11
  • Woodward, Mark10, 11, 12, 13
  • 1 Bordeaux University Hospital, Bordeaux, France , Bordeaux (France)
  • 2 The University of Bordeaux, Bordeaux, France , Bordeaux (France)
  • 3 INSERM Unit 1034, Bordeaux, France , Bordeaux (France)
  • 4 The University of Melbourne and Royal Melbourne Hospital, Melbourne, VIC, Australia , Melbourne (Australia)
  • 5 The University of Milan-Bicocca and Istituto Auxologico Italiano, Milan, Italy , Milan (Italy)
  • 6 Université de Paris, UFR de Médecine, Paris, France , Paris (France)
  • 7 INSERM, Sorbonne Université, Université de Paris, Paris, France , Paris (France)
  • 8 CMC Ambroise Paré, Neuilly-sur-Seine, France , Neuilly-sur-Seine (France)
  • 9 National Heart and Lung Institute, Imperial College, London, UK , London (United Kingdom)
  • 10 The George Institute for Global Health, Sydney, NSW, Australia , Sydney (Australia)
  • 11 The University of New South Wales, Sydney, NSW, Australia , Sydney (Australia)
  • 12 Imperial College London, London, UK , London (United Kingdom)
  • 13 Johns Hopkins University, Baltimore, MD, USA , Baltimore (United States)
Published Article
Cardiovascular Diabetology
Springer (Biomed Central Ltd.)
Publication Date
Jan 04, 2021
DOI: 10.1186/s12933-020-01198-y
Springer Nature


BackgroundIndividuals with diabetes and lower-limb complications are at high risk for cardiovascular and all-cause mortality, but uncertainties remain in terms of cancer-related death in this population. We investigated this relationship in a large cohort of people with type 2 diabetes.MethodsWe used data from the Action in Diabetes and Vascular Disease: PreterAx and DiamicroN Modified-Release Controlled Evaluation (ADVANCE) study. The primary outcome was adjudicated cancer death; secondary outcomes were overall and site-specific incident cancers, determined according to the International Classification of Diseases Code (ICD-10). We compared outcomes in individuals with (versus without) a baseline history of lower-limb complications (peripheral artery disease (PAD) or sensory peripheral neuropathy) using Cox regression models.ResultsAmong 11,140 participants (women 42%, mean age 66 years), lower-limb complications were reported at baseline in 4293 (38%) individuals: 2439 (22%) with PAD and 2973 (27%) with peripheral neuropathy. Cancer death occurred in 316 (2.8%) participants during a median of 5.0 (25th–75th percentile, 4.7–5.1) years of follow-up corresponding to 53,550 person-years and an incidence rate of 5.9 (95% CI 5.3–6.6) per 1000 person-years. The risk of cancer death was higher in individuals with (versus without) lower-limb complication [hazard ratio 1.53 (95% CI, 1.21–1.94), p = 0.0004], PAD [1.32 (1.02–1.70), p = 0.03] or neuropathy (1.41 (1.11–1.79), p = 0.004], adjusting for potential confounders and study allocations. PAD, but not neuropathy, was associated with excess risk of incident cancers.ConclusionsPAD and peripheral neuropathy were independently associated with increased 5-year risk of cancer death in individuals with type 2 diabetes. PAD was also associated with increased risk of incident cancers. Our findings provide new evidence on the non-cardiovascular prognostic burden of lower-limb complications in people with type 2 diabetes.

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