How Prevalent is Anemia in Patients with Diabetic Foot Ulcers?
Anemia is characterized by decreased hemoglobin levels or red blood cells (RBCs), leading to inadequate oxygen delivery. The World Health Organization (WHO) defines anemia as hemoglobin levels less than 12 g/dL in females and less than 13 g/dL in males.1 Adequate blood supply is crucial to prevent weakness, tachycardia, fatigue, lightheadedness, or cold extremities in individuals, all of which are within the common symptomatology of anemia.2 Individuals with diabetes mellitus (DM) are twice as likely to have anemia than individuals without diabetes.3 However, the symptoms of anemia in individuals extend beyond weakness, fatigue, or lightheadedness; anemia in patients with diabetic foot ulcers (DFU) is associated with an increased risk of mortality.3 Decreased hemoglobin levels in patients with both anemia and diabetes can result in inadequate nutrient and oxygen delivery to the ulceration site, limiting the ability to heal. Several studies, including the MEDFUN study—an observational study from March 2016 to April 2017—found that patients with both of these conditions have decreased wound healing (OR=0.52), increased risk of mortality (OR=1.82), and an increased risk of amputation (OR=1.67) in comparison to participants without anemia.3 Patients with DFU compose a significant portion of the patient population typical to podiatric medicine. Determining the prevalence of anemia in patients with DFU may allow for more timely and more adequate treatment, therefore potentially preventing an increased risk of amputation. This review analyzes the prevalence of anemia among patients with DFU and investigates gender disparities and possible correlations between the severity of these conditions.
Methods of Review
On February 8, 2024, the author conducted a PubMed literature search to identify studies evaluating outcomes of patients with DFU. Utilizing different combinations of the search terms, “anemia,” “diabetic,” “foot,” “ulcer,” and “DFU” yielded a result of 76 studies. Meta-analyses and systematic reviews were excluded due to their use of methodologies that may have already summarized findings on this research topic.
Assessment of each study’s relevance looked at the title, year of publication, and abstract, resulting in exclusion of 21 studies. Additionally, 51 studies fell outside the scope and did not meet the exclusion criteria
(Figure 1). Four English language human studies published within the past 10 years were selected for evaluation. Each of the included studies underwent evaluation for standardization, considering factors such as study design, methodology, and statistical analysis and reviewed using Cochrane methodological processes to assess risk of selection bias, detection bias, attrition bias, and performance bias (Figure 2).
Chuan and colleagues conducted a retrospective study from May 2007 to September 2014 in the Chongqing Medical University to assess the relationship between DFU outcome and anemia. The study included 353 participants, a majority of whom were men (n=219), with a mean age of 66.44 years.4 Exclusion criteria included patients with acute complications of diabetes, history of blood transfusion within 3 months, hematological diseases, and autoimmune diseases.4
Operational definitions of DFU and anemia in this study included DFU as being a full-thickness wound, skin necrosis, or gangrene below the ankle, classified by the PEDIS classification.4 Anemia operational definition stemmed from WHO guidelines. The authors followed up with patients for at least 6 months and determined that 53.8% of the patients with DFU and anemia had an adverse outcome in comparison to the control (P < .001). It was not noted if each participant completed their follow-up, indicating some concerns of attrition bias (Figure 3).
Furthermore, logistic regression assessed the independent effects of anemia, revealing a correlation with male sex (P = .001).4 Additionally, coexistence of anemia in patients in that study with DFU was 236 patients, with a prevalence of 66.9%.4 However, the findings cannot be generalized, as this study occurred in a single hospital. A prospective study would be more effective at establishing causality and minimizing confounding variables.
Kumar and team conducted a retrospective study from January 2014 to January 2023 in India to find the prevalence of anemia in hospitalized patients with DFUs. They reviewed cases of 299 patients, predominantly male (n=192) with a mean age of 55.2 years. Hospitalization occurred for patients with DFU if they had cellulitis, leukocytosis, or acidosis.5 These authors used the University of Texas (UT) classification to assess the severity of the DFU. They excluded participants with type 1 diabetes, pancreatic diabetes, and DFU without infection, indicating low attrition bias. The severity of DFU (1B, 2B, 3B) was determined to be statistically significant from the mean hemoglobin levels (10.17g/dL, 9.27g/dL, 8.03g/dL) with P < .0001.5 As the severity of DFU increases, (more pronounced to the bone or joint along with infection), hemoglobin levels decreased.5 The type of infection of a DFU plays a critical role in determining the severity, but this study did not clearly define infection types (cellulitis, sepsis, abscess, or gas gangrene). Follow-up data is essential to evaluate the long-term effects, these authors did not include. Moreover, the workup for anemia was incomplete, as not every patient underwent blood iron level testing.
Yammine and colleagues conducted a retrospective pilot study among patients undergoing surgical treatment for diabetic foot disease (DFD) from January 2019 to December 2019, evaluating the association between hemoglobin level and DFU.6 They studied 37 participants, predominantly male (62%), with a mean age of 72 years. Classified within 2 groups, the cohorts included the experimental (n=16) with an infected DFU, and the control group (n=21) with a non-infected DFU. The exclusion criteria were not sufficient, as patients with blood disorders or autoimmune disorders were included, potentially affecting the results.6 Patients with toenail infections, calluses, vascular or endovascular procedures, or previous history of DFU were excluded, however, these criteria may not be sufficient to establish causality given that this was a retrospective study. Nevertheless, attrition bias is low since all patients within the criteria were included.
The prevalence of anemia was 70.3% (n=26) with a mean hemoglobin level of 11.55 g/dL. No difference in gender was determined among hemoglobin levels (P = .46).6 The authors identified statistical significance among the experimental (10.3 g/dL) and control groups (11.7g/dL) with P = .033, indicating that anemia is associated with an infected DFU.6 The retrospective study by Kumar’s team concluded similar findings that lower hemoglobin levels are associated with an infected DFU.5 While Yammine’s team solely studied infection versus noninfection, Kumar and coworkers concluded that an increased grade of DFU has an association with decreased hemoglobin levels.5,6
Shareef and colleagues conducted a prospective case control study from October 2014 to October 2015 at Baqai Medical University to determine the association of anemia in patients with DFU versus non-DFU. The study included 208 participants, a majority of whom were males (73.9%) over the age of 50 years. Subjects with other apparent causes of anemia, no diabetes, and type I diabetes were excluded, indicating low attrition bias (Figure 5 online). Prevalence of anemia was 85.67% in DFU cases.7 Chuan’s team determined a prevalence of 66.9% but had 353 participants and had a follow up period of at least 6 months4 while Shareef and colleagues didn’t.7 Moreover, those with non-DFUs had higher hemoglobin levels (13.39 g/dL) than those with DFUs (10.49 g/dL) with P < .0001.7 The statistically decreased hemoglobin levels in patients with DFU in comparison to non-DFU has been concluded by 3 out of the 4 studies discussed here.
Concluding Thoughts
After performing this review, the studies in consideration showed a clear connection between worsening DFU severity and lower hemoglobin levels, underlining the importance of monitoring hemoglobin in DFU care. Patients with DFU generally had lower hemoglobin levels than those without DFU, with no gender-based
differences observed. Based on these observations, I feel that podiatrists should integrate regular monitoring of hemoglobin levels, akin to monitoring glucose levels, perfusion status, and neuropathic findings, to reduce the risk of amputations and mortality associated with DFU. Future endeavors should conduct prospective studies with larger sample sizes and adequate follow-up periods to overcome limitations found in previous research.
Robin is a fourth-year podiatric medical student at Samuel Merritt University College of Podiatric Medicine.
References
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2. Freeman AM, Rai M, Morando DW. Anemia screening. 2023. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan–. PMID: 29763080.
3. Gezawa ID, Ugwu ET, Ezeani I, Adeleye O, Okpe I, Enamino M. Anemia in patients with diabetic foot ulcer and its impact on disease outcome among Nigerians: results from the MEDFUN study. PLoS One. 2019;14(12):e0226226. doi: 10.1371/journal.pone.0226226. PMID: 31846473; PMCID: PMC6917259.
4. Chuan F, Zhang M, Yao Y, Tian W, He X, Zhou B. Anemia in patients with diabetic foot ulcer: prevalence, clinical characteristics, and outcome. Int J Low Extrem Wounds. 2016;15(3):220-226. doi: 10.1177/1534734616660224. Epub 2016 Jul 20. PMID: 27440798.
5. Kumar R, Singh SK, Agrawal NK, Kumar U, Kumar S, Supreeth S, Bishnoi A. The prevalence of anemia in hospitalized patients with diabetic foot ulcer (DFU) and the relationship between the severity of anemia and the severity of DFU. Cureus. 2023;15(7):e41922. doi: 10.7759/cureus.41922. PMID: 37583722; PMCID: PMC10424608.
6. Yammine K, Akiki S, Assi C, Hayek F. Anemia prevalence among patients with diabetic foot ulcers necessitating surgery on admission: a preliminary, retrospective comparative study. Wounds. 2022;34(8):216-219. doi: 10.25270/wnds/21073. PMID: 36108203.
7. Shareef AM, Ahmedani MY, Waris N. Strong association of anemia in people with diabetic foot ulcers (DFUs): Study from a specialist foot care center. Pak J Med Sci. 2019;35(5):1216-1220. doi: 10.12669/pjms.35.5.1421. PMID: 31488981; PMCID: PMC6717462.
