Evaluation of Neuropathy, Glycemic Control, and Revascularization as Risk Factors for Future Lower Extremity Amputation among Diabetic Patients.

BACKGROUND

Diabetes mellitus is a major risk factor for progression to lower extremity amputation (LEA) due to progressive neuropathy and glycemia-induced vasculopathy. In this study, we evaluated risk factors for incident LEA type 2 diabetics during a randomized controlled trial and extended post-trial follow-up.

METHODS

The Action to Control Cardiovascular Risk in Diabetes trial randomized 10,251 type 2 diabetics to intensive glycemic control (Hemoglobin A1c (HbA1c) target <6.0%) versus standard glycemic control (HbA1c target 7.0-7.9%). Using backward elimination logistic regression models, we examined relationships between neuropathy using the Michigan Neuropathy Screening Instrument (MNSI) and glycemic control and incident LEA during the clinical trial and subsequent follow-up.

RESULTS

9,746 patients were followed for a mean of 7.9 +/-3.1 (median 8.9) years after randomization. Ninety-eight (1%) participants underwent an incident LEA during the trial or post-trial follow-up period. Baseline demographics and traditional risk factors were examined by incident amputation status. Multivariable models revealed that abnormal 10 gm filament test (HR 4.50, 95% CI 2.92-6.95, P < 0.0001), presence of ulceration (HR 4.22, 95% CI 1.65-10.8, P = 0.0004), abnormal appearance on foot examination (HR 4.75, 95% CI 2.30-9.83, P < 0.0001), and mean postrandomization HbA1c (HR 1.65, 95% CI 1.35-2.00, P < 0.0001) were strongly predictive of LEA when accounting for other common risk factors for amputation.

CONCLUSIONS

In this post hoc analysis of a large randomized controlled population of diabetic patients, we found that components of the MNSI score including presence of ulceration, abnormal appearance of the foot, and 10 gm filament monofilament scoring were strongly predictive of LEA. This adds a valuable clinical tool in the risk stratification of diabetic patients for LEA.