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Multicenter Study
. 2021 Jan 4;20(1):3.
doi: 10.1186/s12933-020-01198-y.

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

Kamel Mohammedi  1   2   3 , Stephen Harrap  4 , Giuseppe Mancia  5 , Michel Marre  6   7   8 , Neil Poulter  9 , John Chalmers  10   11 , Mark Woodward  10   11   12   13
Affiliations
Multicenter Study

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

Kamel Mohammedi et al. Cardiovasc Diabetol. .

Abstract

Background: Individuals 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.

Methods: We 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.

Results: Among 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.

Conclusions: PAD 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.

Keywords: Cancer death; Cancers; Lower-limb complication; Peripheral arterial disease; Peripheral neuropathy; Type 2 diabetes.

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Conflict of interest statement

MW is a consultant to Amgen and Kyowa Kirin. Authors declare no other potential conflict of interest relevant to this article.

Figures

Fig. 1
Fig. 1
Cumulative incidence of cancer death during follow-up according to history of lower-limb complications at baseline. Solid line: absence of complication; dashed line: presence of complication. P values (log-rank test) for comparing absence and presence < 0.0001 for all three complications. LLC lower-limb complications, PAD peripheral artery disease
See this image and copyright information in PMC

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