Association between anemia and the risk of diabetic foot ulcer: A meta-analysis

Abstract

Background: Diabetic foot ulcers (DFUs) are a major complication of diabetes mellitus, and anemia is commonly observed in diabetic patients. However, the relationship between anemia and the risk of developing DFUs remains unclear.

Aim: To investigate the relationship between anemia and the risk of DFUs in diabetic patients through a meta-analysis.

Methods: A systematic search was conducted across PubMed, Embase, and Web of Science databases to identify studies that reported the co-occurrence of anemia and DFUs in diabetic patients. The primary outcome was an association between anemia and DFU risk, expressed as odds ratios (ORs). Secondary outcomes included the risk of DFU per 1-g/dL decrease in hemoglobin and the difference in hemoglobin levels between patients with and without DFU. Statistical analyses were performed using random-effects models to account for heterogeneity.

Results: Sixteen studies involving 170,949 diabetic patients were included in the analysis. The results indicated a significant association between anemia and an increased risk of DFUs (eight studies, n = 166173, OR: 2.72, 95%CI: 1.73-4.25, P < 0.001; I ² = 93%). Subgroup analyses supported consistent findings across various patient characteristics, analytic models, and study quality scores (P for subgroup differences, all > 0.05). Additionally, each 1-g/dL decrease in hemoglobin was associated with an excess risk of DFUs (four studies, n = 2543, OR: 1.65, 95%CI: 1.21-2.27, P = 0.002; I ² = 68%). Furthermore, diabetic patients with DFUs exhibited significantly lower hemoglobin levels compared to those without DFUs (nine studies, n = 3986, mean difference: -2.13 g/dL, 95%CI: -2.58 to -1.68, P < 0.001; I² = 90%).

Conclusion: Anemia can be associated with an increased risk of DFUs in diabetic patients. Monitoring and managing anemia in diabetic population may help mitigate the risk of DFUs, emphasizing the need for early interventions. Further research is required to investigate the underlying mechanisms and potential therapeutic strategies.

Keywords: Anemia; Diabetic foot ulcer; Hemoglobin; Meta-analysis; Risk factor.

Figure 1

Flowchart of database search and study inclusion. DFU: Diabetic foot ulcer; HGB: Hemoglobin.

Figure 2

Forest plots for the meta-analysis of the association between anemia and the risk of diabetic foot ulcers in patients with diabetes. A: Overall meta-analysis; B: Subgroup analysis according to study design; C: Subgroup analysis according to the mean ages of the patients; D: Subgroup analysis according to the proportion of men of the included patients; E: Subgroup analysis according to the analytic models; F: Subgroup analysis according to the Newcastle–Ottawa Scale scores of the included studies. NOS: Newcastle–Ottawa Scale.

Figure 3

Forest plots for the meta-analysis of the secondary outcomes. A: Meta-analysis for the risk of diabetic foot ulcers per 1-g/dL decrease of hemoglobin; B: Meta-analysis comparing serum hemoglobin between diabetic patients with and without diabetic foot ulcer. DFU: Diabetic foot ulcer; DM: Diabetes mellitus.

Figure 4

Funnel plots for estimating the potential publication biases underlying the meta-analyses. A: Funnel plots for the meta-analysis of the association between anemia and the risk of diabetic foot ulcers in patients with diabetes; B: Funnel plots for the meta-analysis comparing serum hemoglobin between diabetic patients with and without diabetic foot ulcers. MD: Mean difference; OR: Odds ratio; SE: Standard error.