HbA1c and Lower Extremity Amputation Risk in Patients With Diabetes: A Meta-Analysis.

In this meta-analysis, we aimed to assess glycosylated hemoglobin (HbA1c) level and lower extremity amputation (LEA) risk in patients with diabetes. Systematic computerized searches of the PubMed and Web of Knowledge were performed. We compared HbA1c level between groups with LEA and without LEA by meta-analysis; we also examined the dose-response relationship between HbA1c level and LEA risk. Sixteen studies were included in the meta-analysis. Eleven studies with 43,566 patients compared HbA1c between groups with and without LEA. The mean HbA1c (%) ranged from 8.3 to 12.5 in the group with LEA and from 7.4 to 11.3 in the group without LEA. The pooled weighted mean difference was 1.110 (95% confidence interval = 0.510-1.709; Z = 3.63, P = .008). The funnel plot was symmetrical, and Begg's test (z = 0.00, P = 1.000) and Egger's test (t = -0.02, P = .984) suggested no significant publication bias. Six studies with 109,933 patients included in the dose-response meta-analysis. The LEA incidence ranged from 0.3% to 14.6% between different HbA1c levels. Dose-response meta-analysis showed statistically significant association between HbA1c and LEA risk (χ(2) = 65.51, P = .000). In linear model, the odds ratio for LEA incidence was 1.229 (95% confidence interval = 1.169-1.292) for every 1% HbA1c increase. In the spline model, the odds ratio of LEA risk increased with HbA1c levels, especially when HbA1c ranged from 5% to 9%. Our meta-analysis indicates that high level of HbA1c is an important risk factor for LEA in patients with diabetes. This evidence supports the strategy for lowering glucose levels to reduce amputation in patients with diabetes.