Foot Ulceration for Diabetes Patients Doubles Mortality Risk

The risks for both cardiovascular disease (CVD) and all-cause mortality among people with diabetes are double those of people without diabetes, the researchers explain. This new systematic review and meta-analysis, examines the influence of diabetic foot ulceration (DFU) on that already-elevated risk.

Jack R.W. Brownrigg, BSc, from St. George's Vascular Institute, London, United Kingdom, writes, "We provide the largest scale evidence to date that patients with DFU have a higher risk of all-cause mortality compared with patients with diabetes but without a history of foot ulceration." In addition, the researchers say, the findings suggest that increased all-cause mortality risk among patients with DFU is not just the result of excess CVD.

The authors analyzed 8 studies published between 1996 and 2011 that reported on a total 17,830 patients with 81,116 patient-years of follow-up. Half of the studies were done in the United States, 2 were done in Europe, 1 in Australasia, and 1 in South-East Asia. Patients with both type 1 and type 2 diabetes were included in all but 1 study, in which all patients had type 2 diabetes.

The 3095 patients with DFU had a significantly longer duration of diabetes, at 12.72 years, compared with the 14,735 patients without DFU (7.19 years; P < .005). The prevalence of coronary artery disease was significantly higher among those with DFU (31.4% vs 14.7%), as was that of both hypertension (57.6% vs 35.7%) and hypercholesterolemia (47.6% vs 11.1%), with all P values < .001.

During follow-up, there were a total 3619 deaths from any cause. The DFU population had a 1.89 pooled relative risk (95% confidence interval [CI], 1.60 - 2.23) for all-cause mortality compared with the patients with diabetes without DFU. Unadjusted rates of all-cause mortality were 99.9 per 1000 person-years for the DFU population vs 41.6/1000 in the diabetes-only group.

Further analysis of a total 3138 patients in 4 studies for whom information on cardiovascular mortality was available showed that rates of fatal myocardial infarction and fatal stroke were also higher among those with DFU, with relative risks of 2.22 (95% CI, 1.09 - 4.53) and 1.41 (95% CI, 0.61 - 3.24), respectively.

However, the overall proportion of deaths resulting from cardiovascular causes was almost the same in the DFU and non-DFU groups: 43.6% of the 117 DFU patients and 44.2% of the 952 diabetes-only patients. "These findings imply that the excess CVD risk observed in DFU patients only partly accounts for the increased mortality rate," the investigators write.

The excess mortality in patients with DFU may also relate to their more advanced stage of diabetes, with greater overall disease burden and noncardiovascular complications of foot ulceration such as sepsis, the authors suggest.

"Our data support the hypothesis that, in order to attenuate the excess mortality associated with DFU, strategies focusing on both more aggressive modification of CVD risk factors and ulcer prevention might be required."

Diabetologia. 2012;55:2906-2912. Abstract