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Foot ulcer severity predicts mortality in type 2 diabetes

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December 15, 2016

In veterans with type 2 diabetes, developing a severe foot ulcer is associated with mortality, even after adjusting for known vascular disease and other comorbidities, according to a retrospective study.

“The association between gangrene and death is important for at least two reasons,” Meghan B. Brennan, MD, a clinical instructor in infectious disease at the University of Wisconsin School of Medicine and Public Health and an advanced research fellow at the Department of Veterans Affairs, and colleagues wrote. “First, it offers a potential causal link between foot ulcers and death. Second, it allows clinicians and researchers to readily identify a subset of patients with diabetic foot ulcers who are at a high risk of early death. On an individual patient–provider level, this allows clinicians to better prognosticate and proactively address impending mortality.”

Brennan and colleagues analyzed data from 66,323 veterans with type 2 diabetes who developed diabetic foot ulcers between 2006 and September 2010, followed until death or January 2012 (mean follow-up time, 27.7 months). Researchers characterized ulcers as early stage, osteomyelitis or gangrene at presentation, and they assessed demographics, comorbidities and health care utilization at baseline. HbA1c, total cholesterol, LDL cholesterol and outpatient systolic blood pressure was averaged during the 12 months preceding the initial ulcer; statin use also was assessed. Researchers used Cox proportional hazard regression analysis to identify independent predictors of death.

At time of ulcer diagnosis, 4.42% of wounds were characterized as osteomyelitis; 3.03% were characterized as gangrene; 1-year, 2-year and 5-year survival rates were 80.8%, 69.01% and 28.94%, respectively. Nearly half the cohort had known coronary artery disease; 15.33% had peripheral artery disease.

Compared with patients with early-stage ulcers, the HR for death for patients with gangrene was 1.7 (95% CI, 1.57-1.83). The effect was higher than that for known CAD, stroke or peripheral artery disease, according to researchers. The HR for death for patients with wounds with osteomyelitis was 1.09 (95% CI, 1.02-1.17) vs. those with early-stage ulcers.

The researchers noted that 70% of patients used statins in the year before ulceration, which was protective (HR = 0.89; 95% CI, 0.86-0.92).

“Only 24% of patients presenting with gangrene carried a prior diagnosis of peripheral arterial disease,” Brennan said. “It is likely that peripheral arterial disease is underdiagnosed or underestimated in this group, despite their frequent interactions with the healthcare system. We need to help clinicians make this diagnosis sooner, which could lead to improved medical management. “

Brennan said that further studies are needed to explore ways to reduce the risk of death among patients with diabetic foot ulcers.

“One promising area is the potential protective role of statins in this high-risk population,” she said. – by Regina Schaffer

For more information:

Meghan B. Brennan, MD, can be reached at the University of Wisconsin School of Medicine and Public Health, 1685 Highland Avenue, Madison, WI 53705; email:

Disclosure: The researchers report no relevant financial disclosures.

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W. Stuart Tucker, Jr.

The power of this report lies in the large population studied (over 66,000 veterans with diabetic foot ulcers) with mean follow-up of 27.7 months and the correlations of mortality with baseline health measures. Mortality rates at 1, 2 and 5 years were high and were highest for ulcers with gangrene vs. ulcers with osteomyelitis vs. early stage ulcers. Statin treatment in the year prior to ulceration was protective of mortality.

While treatment of any diabetic foot ulcer with antibiotics, debridement, revascularization and amputation can in the short term prove lifesaving, longer-term survival is a longer-term proposition that must begin years before the ulcer occurs. Risk-factor modification to control hyperglycemia, lipids, blood pressure, smoking status and, perhaps, systemic inflammation from obesity and other causes will likely have greater impact on mortality than ulcer treatments.  Improving health care access to facilities, providers, medications, diabetes supplies and technology, and foot care should be central to every diabetes care plan for individuals and populations.

From this study, a reader might infer that a diabetic foot ulcer is a flashing indicator of risk for a very rough road ahead. Deeper than the wound, the ulcer is an inflammatory insult with a guarded prognosis for recovery.

W. Stuart Tucker, Jr., MD

Endocrinologist, Randolph Internal Medicine

Carolinas Healthcare System

Charlotte, NC

Disclosure: Tucker reports no relevant financial disclosures.