Correlation of anxiety and depression with pain in patients with diabetic foot ulcers and analysis of risk factors

Abstract

BACKGROUND

Pain often predisposes patients with diabetic foot ulcers (DFUs) to negative emotional states, such as anxiety and depression, which can significantly impair treatment outcomes and recovery. However, very few studies have explored the relationship between anxiety, depression, and pain in DFUs, as well as the associated risk factors.

AIM

To analyze the correlation between anxiety, depression, and pain in patients with DFUs and to identify the associated risk factors.

METHODS

This study included 106 patients diagnosed with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024. The patients’ anxiety levels were evaluated using Zung’s self-rating anxiety scale (SAS), depression status was assessed using Zung’s self-rating depression scale (SDS), and pain intensity was assessed using the visual analog scale (VAS). Subsequently, correlations between SAS, SDS, and VAS scores were analyzed. Univariate and multivariate analyses were conducted to explore the risk factors that contributed to anxiety and depression in patients with DFUs.

RESULTS

Among the 106 patients, 39.62% exhibited anxiety and 43.40% presented with depression. Most patients experiencing anxiety or depression exhibited mild symptoms, with no severe cases observed. Compared with asymptomatic patients, those with anxiety or depression had significantly higher VAS scores. Correlation analysis indicated a significant positive relationship between both SAS and SDS scores and the VAS score. Univariate analysis identified sex, age, Wagner’s grade, presence of other complications, and smoking history as factors significantly associated with anxiety and depression. Multivariate analysis further confirmed that younger age, higher Wagner’s grade, and higher VAS scores were independent predictors of anxiety and depression.

CONCLUSION

This study reveals a significant positive correlation between anxiety, depression, and pain in patients with DFUs. This finding suggests that timely and effective pain intervention may be beneficial in alleviating negative emotions such as anxiety and depression. In addition, younger age (< 50 years), higher Wagner’s grade, and higher VAS scores increase the risk of developing anxiety and depression in this patient population.

Key Words: Diabetic foot ulcers; Anxiety; Depression; Pain; Risk factors

Core Tip: Studies on the correlation between anxiety, depression, and pain in diabetic foot ulcers (DFUs) and analysis of contributing risk factors are limited. This study addresses this gap by providing valuable clinical insights. The findings demonstrate a significant positive correlation between anxiety, depression, and pain in patients with DFUs, highlighting the importance of timely and effective pain management in mitigating these negative emotional states. Furthermore, younger age (< 50 years), higher Wagner’s grade, and high visual analog scale scores were identified as key risk factors for anxiety and depression. Targeted psychological support and proactive interventions for patients exhibiting these characteristics, such as age < 50 years, advanced Wagner’s grades, or high pain levels, can effectively minimize their susceptibility to anxiety and depression.

INTRODUCTION

Diabetic foot ulcers (DFUs), a common complication associated with diabetes mellitus (DM), pose a devastating threat to patients’ health and survival, with potential consequences ranging from infections and amputations to life-threatening situations[1,2]. Epidemiological data indicate that patients with DFUs bear a remarkably high overall mortality risk. Their 5-year survival rate plummets to approximately 50.0%, and those who undergo amputation have an even higher mortality risk[3]. Moreover, the lifetime probability of lower-limb amputation in these patients reaches 20.0%, with a substantial recurrence risk of 65.0% within 3-5 years after diagnosis[4]. In the early phase, DFUs typically manifest as acute foot sensitivity, characterized by pain and tingling sensations. As the disease advances, it gradually progresses to negative symptoms such as toe numbness and weakness. This not only compromises the sensory and motor functions of the patients’ limbs but also undermines their physical balance and stability[5,6]. The etiology of DFUs is intricate, potentially involving neural, vascular, and biomechanical factors[7]. Furthermore, DFUs are often associated with negative psychological states such as anxiety and depression, which are related to factors such as physical pain, restrictions on daily activities, soaring medical expenses, fear of the unknown, feelings of frustration and helplessness, and the looming threat of amputation[8,9]. This psychological burden, in turn, increases the risk of comorbidity with other complications and, to a certain extent, retards the wound-healing process[10]. Previous studies have also elucidated that patients with DFUs have a comparatively high risk of depression. Moreover, depressive manifestations can precipitate suboptimal self-management and a diminished quality of life among these patients[11]. Unseld et al[12] identified a significant association between increased pain levels and psychiatric symptoms in patients with cancer, with pain scores demonstrating a strong correlation with depression. Similarly, Mullins et al[13] highlighted that chronic pain in adults is significantly linked to the severity of both anxiety and depression. These findings indicate a potential relationship between anxiety, depression, and pain in patients with DFUs.

At present, limited studies have evaluated the correlation between anxiety, depression, and pain in DFUs and analyzed the associated risk factors. Therefore, this study attempts to bridge the lacunae in clinical research and aspires to provide novel and efficacious cues for the management of patients with DFUs.

MATERIALS AND METHODS

General data

A total of 106 patients with DFUs who were admitted to Tiantai County People’s Hospital between March 2022 and March 2024 were recruited.

Inclusion criteria: All patients were required to meet both the diagnostic criteria for diabetic foot established by the World Health Organization[14] and Wagner’s grading criteria[15]. In addition, they had to present with unilateral lesions; be at least 18 years old; and have experienced lower-limb infections, ulcers, and deep-seated tissue damage due to neuropathy combined with varying severity of peripheral vascular pathologies to be included in the study.

Exclusion criteria: Patients who had been administered chemotherapy drugs, hormones, or other immunosuppressive agents in the recent period; those with ulcer malignancy and carcinomatous ulcers; those with suboptimal hyperglycemia control; individuals who had encountered significant familial or occupational upheavals in the past 3 months; patients with severe cardiovascular, pulmonary, cerebral, or renal insufficiency; and those with incomplete clinical datasets were excluded.

Detection metrics

Anxiety assessment: Zung’s self-rating anxiety scale (SAS) was utilized to assess the anxiety levels of patients over the week preceding their enrolment in the study[16]. Comprising a total of 20 items, the scale adopts a scoring system ranging from 1 to 4. Specifically, 15 items are scored positively, whereas the remaining 5 are scored in reverse. The raw score is calculated by summing the scores of all 20 items, after which it is multiplied by 1.25, and the integer portion of the product is derived as the standard score. The SAS standard score is interpreted as follows: a score of < 50 indicates no anxiety, 50-59 indicates mild anxiety, 60-69 indicates moderate anxiety, and ≥ 70 suggests severe anxiety. Higher scores indicate more severe anxiety.

Depression evaluation: Zung’s self-rating depression scale (SDS) served as a direct indicator of patients’ depressive experiences over the week preceding their enrolment in the study[17]. The scale comprises 20 items, each rated on a 4-point scale. In this framework, 10 items are scored positively, whereas the other 10 are scored in reverse. The raw score is calculated by summing the scores of all 20 items, and this total is then multiplied by 1.25. The integer part of the resulting product is taken as the standard score. Based on the Chinese norm, a standard score of ≥ 53 indicates depression, with the severity increasing along with the score. More precisely, a score of 53-62 points indicates mild depression, 63-72 denotes moderate depression, and ≥ 73 indicates severe depression.

Pain measurement: The intensity of pain experienced by patients was assessed using the visual analog scale (VAS)[18]. This scale employs a scoring range from 0 to 10 points, with higher scores indicating greater pain.

Statistical analysis

All statistical analyses were performed using IBM SPSS Statistics version 24.0 (IBM Corp., Armonk, NY, United States) or GraphPad Prism 7. Measurement data were expressed as the mean ± SE of the mean. Numerical data were presented as the number of cases along with their corresponding percentages (%). When comparing between groups, the χ² test or the corrected χ² test was utilized. The Pearson correlation coefficient was applied to explore the relationships between the SAS, SDS, and VAS scores in patients with DFUs. Multivariate binary logistic regression analysis was employed to analyze the risk factors associated with anxiety and depression in these patients. A P value < 0.05 was considered statistically significant.

RESULTS

Anxiety and depression conditions in patients with DFUs

For the 106 patients with DFUs, the mean SAS score was 47.12 ± 7.77. Among them, 39.62% exhibited anxiety, with 33.02% presenting with mild anxiety and 6.60% with moderate anxiety. Regarding depression, the mean SDS score was 51.17 ± 5.71. Patients with depression accounted for 43.40% of the cohort, with 40.57% showing mild depression and 2.83% showing moderate depression. Detailed information is presented in Table 1.

Table 1 Anxiety and depression conditions in patients with diabetic foot ulcers, mean ± SD, n (%).

Psychologic status	None	Mild	Moderate	Severe
SAS	64 (60.38)	35 (33.02)	7 (6.60)	0 (0.00)
Average score	47.12 ± 7.77
SDS	60 (56.60)	43 (40.57)	3 (2.83)	0 (0.00)
Average score	51.17 ± 5.71

SAS: Self-rating anxiety scale; SDS: Self-rating depression scale.

Pain levels in patients with DFUs

An assessment of pain levels in patients with DFUs indicated that the VAS scores of the anxiety group were significantly higher than those of the non-anxiety group (P < 0.05). Similarly, patients in the depression group exhibited markedly higher VAS scores compared to those without depression (P < 0.05). Detailed results are presented in Figure 1.

Figure 1 Pain levels in patients with diabetic foot ulcers. A: Visual analogue scale scores of patients without and with anxiety; B: Visual analog scale scores of patients without and with depression. ^aP < 0.05 denotes a significant difference compared to patients without anxiety or depression. VAS: Visual analog scale.

Correlations of SAS and SDS with VAS scores in patients with DFUs

Using Pearson correlation coefficient analysis to investigate the interrelationships among SAS, SDS, and VAS scores in patients with DFUs, a significant positive correlation was found between SAS and VAS scores (r = 0.540, P < 0.001). Similarly, a significant positive correlation was found between SDS and VAS scores (r = 0.457, P < 0.001). Detailed data are presented in Table 2.

Table 2 Correlations of self-rating anxiety scale and self-rating depression scale with visual analog scale scores in diabetic foot ulcer patients.

Correlation	r value	P value
SAS and VAS	0.540	< 0.001
SDS and VAS	0.457	< 0.001

VAS: Visual analog scale; SAS: Self-rating anxiety scale; SDS: Self-rating depression scale.

Univariate analysis of anxiety and depression in patients with DFUs

Among the 106 patients with DFUs, 62 exhibited symptoms of anxiety or depression, whereas 44 did not show such manifestations. Univariate analysis revealed that variables such as sex, age, Wagner grade, presence of concomitant complications, and smoking history were all intricately associated with anxiety and depression in such patients (P < 0.05). Detailed findings are presented in Table 3.

Table 3 Univariate analysis of anxiety and depression in patients with diabetic foot ulcers, n (%).

Variable	No anxiety or depression (n = 44)	Anxiety or depression (n = 62)	χ2	P value
Sex			5.925	0.015
Male	29 (65.91)	26 (41.94)
Female	15 (34.09)	36 (58.06)
Age (years)			9.947	0.002
< 50	14 (31.82)	39 (62.90)
≥ 50	30 (68.18)	23 (37.10)
Course of diabetes mellitus (years)			0.452	0.798
< 5	11 (25.00)	19 (30.65)
5-10	20 (45.45)	25 (40.32)
> 10	13 (29.55)	18 (29.03)
Wagner’s grade			4.127	0.042
I-III	32 (72.73)	33 (53.23)
IV-V	12 (27.27)	29 (46.77)
Other complications			5.632	0.018
Without	34 (77.27)	34 (54.84)
With	10 (22.73)	28 (45.16)
Married			0.431	0.512
No	22 (50.00)	27 (43.55)
Yes	22 (50.00)	35 (56.45)
Smoking history			5.130	0.024
Yes	31 (70.45)	30 (48.39)
No	13 (29.55)	32 (51.61)
Alcoholism history			0.800	0.371
No	30 (68.18)	37 (59.68)
Yes	14 (31.82)	25 (40.32)

Multivariate analysis of anxiety and depression in patients with DFUs

In a comprehensive investigation into the determinants of anxiety and depression in patients with DFUs, factors that had demonstrated significant differences in the univariate analysis, along with the VAS scores, were designated as independent variables, whereas the presence or absence of anxiety and depression was established as the dependent variable. The above variables were assigned appropriate numerical values for the subsequent binary logistic regression analysis. The results, based on a robust statistical foundation, clearly indicated that age, Wagner’s grade, and VAS score emerged as independent factors significantly associated with the presence of anxiety and depression in patients with DFUs (P < 0.05). Detailed data are presented in Tables 4 and 5.

Table 4 Assignments.

Variable	Variable	Assignment
Sex	X1	Male = 0, female = 1
Age (years)	X2	< 50 = 0, ≥ 50 = 1
Wagner’s grade	X3	I-III = 0, IV-V = 1
Other complications	X4	Without = 0, with = 1
Smoking history	X5	Without = 0, with = 1
VAS	X6	Continuous variable

VAS: Visual analog scale.

Table 5 Multivariate analysis of anxiety and depression in patients with diabetic foot ulcers.

Variable	β	SE	Wald	P value	OR	95%CI
Sex	0.092	0.498	0.034	0.854	1.096	0.413-2.909
Age (years)	−1.048	0.463	5.119	0.024	0.351	0.141-0.869
Wagner’s grade	1.097	0.517	4.512	0.034	2.996	1.089-8.264
Other complications	0.921	0.499	3.409	0.065	2.512	0.945-6.677
Smoking history	0.868	0.501	3.006	0.083	2.382	0.893-6.356
VAS	0.473	0.201	5.556	0.018	1.605	1.083-2.378

VAS: Visual analog scale; OR: Odds ratio; CI: Confidence interval.

DISCUSSION

DFU is a multifaceted and intricate disease that typically presents with ulceration and infection. The epidermis and dermis of the foot endure significant damage, resulting in a breach of the cutaneous envelope, exposing the aseptic structures and progressively evolving into a full-thickness pathological state[19]. Numerous investigations have indicated that negative emotional states, such as anxiety and depression, can adversely affect clinical outcomes in these patients. Consequently, DFU management should not be confined merely to curbing the progression of the disease but also extended to safeguarding the psychological well-being of patients[20,21]. This study aimed to analyze the anxiety and depression status of patients with DFUs and further investigate the associated risk factors. Such efforts hold significant clinical importance for enhancing the clinical outcomes of these patients.

In this study, 39.62% of the 106 patients diagnosed with DFUs exhibited anxiety symptoms, whereas 43.40% presented with signs of depression. Although the overall patient cohort was anxiety-free, they exhibited signs of mild depression. When compared with patients without anxiety and depression, those with anxiety or depression showed comparatively higher pain levels. Furthermore, in patients with DFUs, a significant positive correlation was observed between SAS, SDS, and VAS scores. Ma et al[22] posited that the pain levels experienced by patients with DFUs influence their disease perception, which, in turn, is significantly associated with anxiety and depression, indirectly reflecting the potential relationship among pain, anxiety, and depression. Univariate analysis further revealed that sex, age, Wagner’s grade, presence of other comorbidities, and a history of smoking were all significantly associated with the presence of anxiety and depression in patients with DFUs. Al-Ayed et al[23] reported that female patients, individuals with lower educational attainment, those taking oral hypoglycemic agents and undergoing insulin therapy, those with a low income, and those who had experienced several diabetes-related complications were more likely to exhibit high levels of anxiety or depression. This finding corroborates the results of this study. Binary logistic multivariate regression analysis further demonstrated that age, Wagner’s grade, and VAS scores were independently associated with the presence of anxiety and depression in patients with DFUs. Among these factors, advanced age (≥ 50 years) emerged as a protective factor against the development of anxiety and depression in this patient cohort. Conversely, Wagner’s grade and VAS scores were identified as significant risk factors. Patients aged < 50 years, who are typically part of the actively employed workforce, are frequently burdened with substantial economic stressors contributing to increased psychological stress. In contrast, relatively older patients tend to receive both financial and emotional support from their families, which, to a certain extent, helps alleviate their psychological stress[24]. Patients with high Wagner’s grades typically present with more severe clinical manifestations and face greater disease-related suffering and pain, leading to increased physical and emotional distress, which is not conducive to the dissipation of negative emotions[25]. Similarly, patients exhibiting high VAS scores usually experience more severe pain, contributing further to emotional deterioration through the same mechanism[26]. Ahmad et al[27] reported that anxiety and depression affected 37.7% and 39.6%, respectively, of a cohort of 260 patients diagnosed with DFUs. Significantly, age < 50 years, female sex, current smoking, and presence of three or more comorbidities were identified as risk factors for the development of anxiety and depression among these patients. This finding bears a striking resemblance to the outcomes of the present study. Furthermore, previous research has demonstrated that providing social support to patients with DFUs can effectively mitigate the severity of their depressive symptoms, indicating that effective social support interventions can be considered in addition to psychological interventions for patients[28].

This study has several limitations that warrant further investigation. First, potential confounding factors were not fully controlled in the multivariate analysis. Addressing these factors in future analyses could improve the accuracy of the results and minimize bias. Second, the sample size was relatively small. Expanding the research to include larger, multicenter cohorts would enable more sophisticated statistical analyses and improve the generalizability of the findings. Lastly, incorporating a control group (e.g., patients with DM but without DFUs) to compare anxiety and depression levels could further strengthen the conclusions. Thus, future research should address these limitations to provide more comprehensive and reliable insights.

CONCLUSION

In summary, patients with DFUs face a discernible risk of experiencing anxiety and depression, with a positive correlation firmly established between anxiety and depression and pain levels. Employing pain-management strategies for these patients can effectively relieve their psychological distress. Moreover, age, Wagner’s grade, and VAS scores emerge as independent factors influencing anxiety and depression in this patient cohort. Notably, targeted psychological monitoring, combined with proactive intervention strategies, tailored to patients aged < 50 years, those presenting with a high Wagner’s grade, and individuals with high VAS scores, can substantially reduce their risk of developing anxiety and depression. The results of this study emphasize the critical need to integrate pain management and psychological support into the care of patients with DFUs. By identifying key risk factors such as younger age, higher Wagner grade, and high VAS scores, healthcare providers can tailor personalized pain intervention strategies for high-risk individuals, thereby improving their physical and mental health outcomes. Furthermore, adopting a multidisciplinary, integrated care model could offer holistic physiological and psychological support, ultimately enhancing the quality of life, treatment adherence, and overall clinical outcomes among patients with DFU, ultimately leading to better overall health outcomes.