A pproximately 60,000 nontraumatic diabetic amputation procedures are performed annually in the United States.^1,2 The risk of a patient with diabetes succumbing to a nontraumatic lower-extremity amputation is 5% to 15%. This risk represents a 15-fold increase in contrast to the nondiabetic population. Medical professionals are rigorously searching for reasons to explain this phenomenon in order to reduce this risk of amputation.³
The literature reports risk factors predisposing patients with diabetes to limb loss. Reiber et al.⁴ identified specific risk factors asserted to increase the chances for nontraumatic amputation. These risks include increased age, male gender, African-American race, presence of neuropathy and/or peripheral vascular disease (PVD), type of diabetes (greater risk in noninsulin-dependent diabetes mellitus), poor glycemic control including elevated hemoglobin (Hgb) A1C level, clinical duration of diabetes, and prior history of ulcers, retinopathy, and previous amputations.⁴ In an earlier article, Reiber et al.⁵ presented pathophysiologic risk factors for lower-extremity amputation including presence of neuropathy, PVD, hypertension, smoking, hyperlipidemia, propensity for infection secondary to trauma, ulcers, and ingrown nails. Data provided evidence that 80% to 85% of lower-extremity amputations are the result of chronic ulcerations and faulty wound healing.^6,7 Therefore, physiologic parameters of poor wound healing, such as poor plasma albumin and low plasma zinc levels, have also been identified as risk factors for nontraumatic amputation in patients with diabetes.⁵
In a continuing effort to better understand factors precipitating amputation in patients with diabetes, various paradigms have been developed. As a result, “causal pathways” relating various common risk factors have been described. These pathways incorporate the major risk factors of ischemia and neuropathy with specific component causes and sufficient causes of amputation.⁸ Component causes of amputation include trauma, ulceration, and/or failure to heal, whereas sufficient causes include gangrene and infection.
A multispecialty, interdisciplinary clinic was created in 1996 at the Louisiana State University Health Sciences Center—Shreveport to address the rising number of patients with diabetes presenting with lower-extremity wounds and at risk for amputation. Despite adherence to treatment pathways addressing known risk factors increasing the risk of amputation, the rate of limb loss secondary to diabetes remained relatively unchanged over a 5-year period. The major risk factors observed in the authors’ population were similar to those previously reported in the literature.^4–7 However, the authors observed many patients with diabetes who possessed the major risk factors of neuropathy and PVD yet did not develop any component causes, such as trauma, ulceration, and/or failure to heal.
Furthermore, many patients with confirmed component causes did not advance to major lower-limb amputations. The underlying factors that protected these patients with diabetes and risk factors of neuropathy and/or PVD from limb loss were unknown. Therefore, it was the intent of this investigation to identify additional factors differentiating those patients with diabetes who advanced to amputation from those with similar risk factors who did not succumb to amputation.

Research Design and Methods

The design of this study was a retrospective, exploratory data analysis using existing patient information from the institutional patient records. The records of 50 patients with diabetes and documented presence of the major risk factors neuropathy and/or PVD that had undergone major lower-extremity amputations between 1997 and 2002 and 30 patients with diabetes who likewise had neuropathy and/or PVD but had not undergone major limb loss were examined.