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Association between Diabetic Foot Ulceration and Premature Death

Evidence is emerging that diabetic foot ulceration is associated with greater risk of premature death…. 

Diabetes is an established risk factor for several causes of death, including ischemic heart disease, stroke, renal disease, infectious diseases and several cancers. Estimates based on analysis of 123,205 deaths among 820,200 individuals suggest an adjusted hazard ratio of 1.80 (Confidence interval 95%) for death from any cause compared to persons without diabetes.

A meta-analysis of 3,619 deaths among individuals with diabetes and those who also had a history of foot ulcers reported a high risk of mortality from any cause in those patients who had diabetic foot ulcers; relative risk was 1.89. This correlation led to further studies to evaluate differences in overall mortality and method of death among adults with diabetes; specifically comparing those with a history of diabetic foot ulcers (DFU) to those without.

 A single-center, retrospective study was done of all patients attending a diabetic foot clinic between January 2009 and December 2010 in the United Kingdom. As part of established care in the UK, all patients with DFU are referred from the community into secondary foot care clinics where they are managed by a multidisciplinary team, including diabetes physicians, microbiologists, vascular surgeons, and podiatrists. These patients are typically seen on a weekly basis until the ulcer heals. The control group consisted of diabetic patients attending a general diabetes clinic during the same time period. Patients attending these clinics are generally seen twice a year to optimize blood glucose and manage any disease related complications.

Cause of death was obtained by reviewing death certificates and verified against case notes and hospital records. Diabetic foot related deaths were defined as those directly related to the foot ulcer (i.e. sepsis) and deaths resulting from complications after admission to the hospital or within 30 days of admission to the hospital for DFU. The causes of death were classified into CVD specific and non-CVD mortality according to the International Classification of Diseases, Ninth Edition.

A total of 869 patients were included in the study; 436 in the diabetes group and 433 in the DFU group. Median follow-up duration in the DFU group was 3.7 years compared with 3.6 years in the diabetes only group. Baseline characteristics were similar between the two groups with the exception that there were more males in the group that had foot ulcers. Patients with DFU were more often dyslipidemic with a history of smoking, although presence of hypertension was not significantly different.

The crude mortality rates in the groups with or without diabetic foot were 27.0% and 6.4% respectively. Patients with DFU were shown to have an approximate 3 fold increased risk of CVD-specific mortality. The two year risk of cardiovascular death in the DFU group was 3% compared with 1% in the patients with diabetes alone. The corresponding risks for nonvascular deaths were higher, at 15% and 3% for the DFU and diabetes alone groups, respectively.

These findings indicate that foot ulceration is associated with premature death from all causes. On average, a person with diabetes who developed foot ulceration was around 3 years younger at the time of death than a counterpart with diabetes. In addition, the association between DFU and premature mortality observed in the study is additive to that associated with diabetes itself, for which the reduction in life expectancy is about 6 years.

Several mechanisms may explain the link between DFU and increased overall mortality. Active ulceration has been shown to cause numerous biologic responses most notably chronic inflammation, which has been shown to play a role in the development and progression of atherosclerosis. DFU is also associated with microangiopathy and macroangiopathy. PAD is a consistent independent predictor of CVD and all-cause mortality and is present in around 50% of patients with DFU.

If active ulceration and its inflammatory sequelae contributes to overall mortality, then it is important to aim strategies at preventing ulceration.

Practice Pearls:
  • The crude mortality rates in the groups with or without diabetic foot were 27.0% and 6.4% respectively.
  • A person with diabetes who developed foot ulceration was around 3 years younger at the time of death than a counterpart with diabetes.

Brownrigg, Jack R.W., Griffin, Michelle, Hughes, Cian O., et al. Influence of foot ulceration on cause-specific mortality in patients with diabetes mellitus. Journal of Vascular Surgery. May 24, 2014.