Clinical features of malnutrition in hospitalized patients with type 2 diabetes mellitus-related diabetic foot ulcers: A retrospective study

Abstract

BACKGROUND

Type 2 diabetes mellitus is a global health challenge that often leads to complications such as diabetic foot ulcers (DFUs). Although malnutrition is a common feature of hospitalized patients with type 2 diabetes mellitus, data on malnourished patients also diagnosed with DFUs are limited.

AIM

To determine the clinical features of malnutrition in this high-risk population.

METHODS

This retrospective study included patients diagnosed with DFUs who were hospitalized between January 2020 and December 2025. We analyzed clinical data derived from electronic medical records, with patients being categorized into malnutrition and non-malnutrition groups based on nutritional status at admission and compared with respect to demographic, clinical, and outcome variables. Univariate and multivariate logistic regression analyses were performed to identify factors of interest, and receiver operating characteristic curves were used to evaluate the predictive value of significant risk factors.

RESULTS

In total, 268 eligible patients were enrolled in this study, of whom 96 and 172 were assigned to the malnutrition and non-malnutrition groups, respectively. Univariate analysis identified significant between-group differences for six factors, namely, age, duration of diabetes, serum albumin, triglycerides, hemoglobin, glycated hemoglobin, and multidrug-resistant organisms (MDROs; P < 0.05). Multivariate analysis revealed that age (> 65 years; P = 0.004), serum albumin (< 36.6 g/L; P = 0.014), hemoglobin (< 111.2 g/L; P < 0.001), glycated hemoglobin (> 7.1%; P < 0.001), and MDROs (P < 0.006) were independent risk factors for malnutrition. Furthermore, compared with the non-malnutrition group, patients in the malnutrition group had a longer mean hospital stay and lower rates of wound healing within 60 days (P < 0.05).

CONCLUSION

To improve the clinical outcomes of malnourished hospitalized patients with DFUs, early intervention should be provided to those with risk factors such as older age, depleted hemoglobin, and MDRO infections.

Key Words: Malnutrition; Diabetic foot ulcer; Type 2 diabetes mellitus; Nutritional risk screening; Clinical outcomes

Core Tip: Malnutrition is a critical yet underrecognized issue in hospitalized patients with type 2 diabetes mellitus-related diabetic foot ulcers, directly impacting clinical outcomes. In this retrospective study of 268 patients with type 2 diabetes mellitus-related diabetic foot ulcers, malnutrition was identified in 35.8% and was independently associated with age > 65 years, serum albumin < 36.6 g/L, hemoglobin < 111.2 g/L, glycated hemoglobin > 7.1%, and multidrug-resistant organisms. Malnourished patients experienced longer hospital stays and lower 60-day wound healing rates. Early nutritional assessment and targeted intervention for these modifiable risk factors are essential to improve prognosis in this high-risk population.

INTRODUCTION

Type 2 diabetes mellitus (T2DM) is the most common type of diabetes, accounting for more than 90% of cases globally[1]. It is a metabolic disorder caused by a combination of genetic and lifestyle factors. The underlying mechanism of T2DM involves defects in insulin secretion or insulin function[2]. Over the past several decades, the world has witnessed a significant increase in the prevalence of T2DM and the enormous economic burden it has caused[3-5]. This trend leads to an increase in diabetes-related complications. Diabetic foot ulcers (DFUs) are a common complication, affecting up to one-third of patients with long-term or poorly managed diabetes[6]. The global prevalence of DFUs is 6.3%, corresponding to an annual incidence of approximately 18.6 million new cases[7]. DFUs are often characterized by prolonged wound healing and can result in poor prognosis, such as high recurrence rate after ulcer healing, doubled subsequent risk of amputation, and even increased mortality rate. Consequently, DFUs impose substantial clinical and financial burden on healthcare systems[8].

Patients with T2DM are at increased risk of malnutrition, a condition characterized by calorie and protein deficits that is not deemed a medical priority and is often under-recognized[9-11]. However, it is prevalent and remains a serious health concern among hospitalized patients, as it is linked to numerous unfavorable clinical outcomes, such as muscle loss, impaired wound healing, decreased bone mass, immune dysfunction, increased treatment cost, prolonged hospitalization, and increased morbidity and mortality[12,13]. Previous studies have shown that malnutrition negatively influences the prognosis of DFUs, mainly focusing on prolonged wound healing and increased risk of infection[14,15]. However, there remains a lack of sufficient data regarding risk factors and outcomes of malnutrition among patients with DFUs.

Therefore, the aim of our study was to identify the clinical features of malnutrition in patients with T2DM hospitalized for DFUs, with the goal of improving clinical assessment and management to enhance patient outcomes.

MATERIALS AND METHODS

Study design and eligibility

This retrospective study included patients with T2DM hospitalized with DFUs at the Affiliated People’s Hospital of Ningbo University (Zhejiang Province, China) between January 2020 and December 2025. Data were extracted from electronic medical records. The inclusion criteria were as follows: Age > 18 years, T2DM diagnosis, and DFU diagnosis. Patients were excluded if they had a terminal malignancy, mental illness, or pregnancy, or if they were lost to follow-up. This study was conducted in accordance with the principles of the Declaration of Helsinki, and ethical approval was obtained from the Ethics Committee of the Affiliated People’s Hospital of Ningbo University (Approval No. 2026-024).

Nutritional assessment

Malnutrition was diagnosed in two steps. First, all patients were assessed for nutritional risk using the Nutritional Risk Screening 2002 (NRS-2002) upon admission. The NRS-2002 is an evidence-based tool developed by the European Society for Clinical Nutrition and Metabolism to identify hospitalized patients at risk of malnutrition[16,17]. It evaluates nutritional risk based on three parameters: Nutritional status (including weight loss, body mass index S[BMI], and recent food intake), disease severity, and patient age. The NRS-2002 is widely recognized as a more reliable nutritional screening tool than traditional methods, because it integrates disease severity and current nutritional status. According to the NRS-2002, patients with scores ≥ 3 are at risk of malnutrition, whereas those with scores < 3 are not at risk[18]. Second, patients at risk of malnutrition were further evaluated using the Global Leadership Initiative on Malnutrition approach[17]. The widely accepted Global Leadership Initiative on Malnutrition criteria define malnutrition in adults based on a combination of phenotypic and etiologic factors. The phenotypic criteria include unintentional weight loss, low BMI, and reduced muscle mass. The etiologic criteria encompass reduced food intake or assimilation alongside the presence of inflammation or an underlying disease. To diagnose malnutrition, at least one phenotypic and one etiologic criterion must be met. Phenotypic criteria were as follows: Non-volitional weight loss; low BMI; and reduced muscle mass. Etiologic criteria were as follows: Reduced food intake or assimilation and disease burden or inflammation.

Definition of DFUs

DFUs were defined as ulceration, infection, and/or destruction of deep tissues in patients with diabetes, typically occurring alongside underlying neuropathy or peripheral arterial disease[19].

Treatment of DFUs

Imaging studies, such as lower-limb radiography or magnetic resonance imaging, were performed. Lower limb blood supply was evaluated using the ankle-brachial index and vascular ultrasound. Neuropathic and mild-to-moderate ischemic ulcers were managed conservatively with immobilization and offloading. Patients with severe ischemic wounds first underwent vascular interventional or bypass surgery to improve foot perfusion. Conservative management included blood glucose, blood pressure, and lipid level control, alongside antiplatelet therapy. Bacterial cultures were obtained, and antibiotics were administered accordingly. Local wound debridement was performed to promote granulation tissue formation and wound healing. Patients with extensive necrosis or uncontrollable infection underwent minor or major amputation.

Discharge criteria

Patients met the discharge criteria upon achieving infection control and maintaining fasting capillary blood glucose levels between 4.4 mmol/L and 7.0 mmol/L, and non-fasting levels below 10 mmol/L.

Follow-up regimen

Patients were followed up every 2 weeks to 4 weeks after discharge, provided wound healing progressed. The 60-day post-discharge follow-up involved either outpatient clinic visits or telephone consultations. Based on clinical signs and symptoms, follow-up frequency was increased to weekly or biweekly intervals if necessary. At each visit, physicians examined wound healing progress, adjusted debridement and dressing protocols, and ensured patient adherence to offloading. Follow-up laboratory tests included glycated hemoglobin (HbA1c), routine biochemical panels, complete blood counts, and C-reactive protein (CRP).

Criteria for wound healing

Wound healing criteria included confirmed complete epithelialization, a ≥ 50% reduction in wound area at 4 weeks post-discharge, consistent reduction in wound depth, granulation tissue formation, reduced exudate, and absence of infection.

Data collection

Following nutritional assessment, patients were stratified into malnourished and non-malnourished groups. The following demographic and clinical data were collected: Age, sex, marital status, residence status, smoking status, alcohol consumption, diabetes duration, and history of hypertension. Baseline laboratory parameters were extracted from the medical records, including serum albumin, CRP, triglycerides, high-density lipoprotein, hemoglobin, HbA1c, estimated glomerular filtration rate, creatinine, fasting blood glucose, and multidrug-resistant organism (MDRO) infection. The following treatment outcomes were also documented: Lower-limb or toe amputation during hospitalization, length of hospital stay, in-hospital death, and wound healing within 60 days.

Statistical analysis

Continuous variables are expressed as the mean ± SD, and categorical variables as frequencies. Categorical data were compared using the χ² test or Fisher’s exact test, whereas continuous variables were compared using the Student’s t-test or Mann-Whitney U test. Univariate exact logistic regression analysis was conducted to identify risk factors for malnutrition in patients with DFUs. Variables demonstrating a univariable association with the outcome (P < 0.10) were included in a multivariable logistic regression model. Receiver operating characteristic (ROC) curve analysis was performed to assess the discriminative ability of the binary logistic regression model and determine the optimal cutoff points for the identified risk factors. All analyses were conducted using SPSS (version 22.0; IBM Corp., Armonk, NY, United States), with statistical significance set at P < 0.05.

RESULTS

Baseline characteristics

This study included 268 patients aged 65.6 ± 10.3 years. Of these, 96 patients were classified into the malnutrition group and 172 into the non-malnutrition group, corresponding to a malnutrition prevalence of 35.8%. The study design and analytical workflow are presented in Figure 1.

Figure 1 Patients enrollment workflow.

A comparison of demographic and clinical characteristics between the groups revealed no significant differences in sex, marital status, residence, alcohol use, smoking status, hypertension, CRP, high-density lipoprotein, estimated glomerular filtration rate, creatinine, or fasting blood glucose (P > 0.05). Statistically significant differences were observed, however, in age, diabetes duration, serum albumin, triglyceride, hemoglobin, HbA1c, and MDROs colonization (P < 0.05; Table 1).

Table 1 Demographics and clinical characteristics of patients between the two groups, mean ± SD/n (%).

	Malnutrition group (n = 96)	Non-malnutrition group (n = 172)	P value
Age (years)	68.5 ± 10.7	64.0 ± 9.8	0.001
Sex			0.591
Male	66 (68.8)	112 (65.1)
Female	30 (31.3)	60 (34.9)
Marital status			0.726
Married	92 (95.8)	167 (97.1)
Single/divorced	4 (4.2)	5 (2.9)
Residence			0.859
City	81 (84.4)	147 (85.5)
Rural	15 (15.6)	25 (14.5)
Alcohol	11 (11.5)	18 (10.5)	0.839
Smoking	20 (20.8)	42 (24.4)	0.548
Diabetes duration (years)	11.0 ± 2.9	10.3 ± 3.0	0.046
Hypertension	50 (52.1)	94 (54.7)	0.703
Serum albumin (g/L)	35.3 ± 8.8	39.0 ± 9.2	0.002
CRP (mg/L)	20.1 ± 8.6	21.6 ± 9.8	0.216
Triglyceride (mmol/L)	3.2 ± 1.0	2.9 ± 1.1	0.025
HDL (mmol/L)	1.1 ± 0.4	1.0 ± 0.3	0.735
Hemoglobin (g/L)	104.5 ± 21.1	116.1 ± 24.8	< 0.001
HbA1c (%)	8.1 ± 1.2	6.7 ± 1.1	< 0.001
eGFR (mL/minute/1.73 m2)	76.3 ± 35.6	72.5 ± 35.1	0.388
Creatinine (μmol/L)	68.8 ± 28.3	71.2 ± 26.4	0.500
Fasting blood glucose (mmol/L)	6.3 ± 2.2	6.1 ± 2.1	0.444
MDROs	46 (47.9)	50 (29.1)	0.002

CRP: C-reactive protein; eGFR: Estimated glomerular filtration rate; HbA1c: Glycated hemoglobin; HDL: High-density lipoprotein; MDRO: Multidrug-resistant organism.

Risk factors for malnutrition

Optimal cutoff values for the identified risk factors were determined based on ROC curve analysis by maximizing the Youden index. The values thus obtained were as follows: Age (65 years), diabetes duration (8.9 years), and serum albumin (36.6 g/L), triglyceride (2.0 mmol/L), hemoglobin (111.2 g/L), and HbA1c (7.1%) levels. Having determined the values for these continuous variables, they were subsequently converted to categorical variables for further analysis. The results obtained for the univariate analysis of statistically significant variables including age, diabetes duration, serum albumin, triglycerides, hemoglobin, HbA1c, and MDROs are presented in Table 2. Among these variables, those assigned a P-value < 0.10 were included in a subsequent multivariate logistic regression analysis. Multicollinearity among independent variables was assessed using the variance inflation factor (VIF), with a VIF value > 5 being considered indicative of significant collinearity. However, we detected no occurrences of significant multicollinearity (all VIFs < 5).

Table 2 Univariate logistic regression for risk factors for malnutrition in patients hospitalized with diabetic foot ulcers.

	B	SE	Walds	OR	95%CI	P value
Age (> 65 years)	0.043	0.013	11.048	1.044	1.018-1.071	0.001
Diabetes duration (> 8.9 years)	0.087	0.044	3.924	1.090	1.001-1.188	0.048
Serum albumin (< 36.6 g/L)	1.043	1.427	0.534	2.838	0.713-46.528	0.002
Triglyceride (> 2.0 mmol/L)	0.272	0.122	4.946	1.312	1.033-1.668	0.026
Hemoglobin (< 111.2 g/L)	1.241	0.268	21.426	3.460	2.046-5.853	< 0.001
HbA1c (> 7.1%)	1.056	0.147	51.635	2.874	2.155-3.834	< 0.001
MDROs	0.809	0.264	9.349	2.245	1.337-3.796	0.002

CI: Confidence interval; DFU: Diabetic foot ulcer; HbA1c: Glycated hemoglobin; MDRO: Multidrug-resistant organism; OR: Odds ratio.

Multivariate analysis identified the following independent risk factors for malnutrition in hospitalized patients with DFUs: Age > 65 years [odds ratio (OR) = 1.047, 95% confidence interval (CI): 1.015-1.081, P = 0.004], serum albumin < 36.6 g/L (OR = 3.229, 95%CI: 1.605-6.494, P = 0.014), hemoglobin < 111.2 g/L (OR = 3.722, 95%CI: 1.861-7.445, P < 0.001), HbA1c > 7.1% (OR = 3.016, 95%CI: 2.175-4.183, P < 0.001), and presence of MDROs (OR = 2.575, 95%CI: 1.311-5.058, P = 0.006; Table 3).

Table 3 Multivariate logistic regression for risk factors for malnutrition in patients hospitalized with diabetic foot ulcers.

	B	SE	Walds	OR	95%CI	P value
Age (> 65 years)	0.046	0.016	8.111	1.047	1.015-1.081	0.004
Diabetes duration (> 8.9 years)	0.174	0.057	9.311	1.191	1.064-1.332	0.062
Serum albumin (< 36.6 g/L)	1.172	0.357	10.807	3.229	1.605-6.494	0.014
Triglyceride (> 2.0 mmol/L)	0.257	0.163	2.482	1.293	0.939-1.781	0.115
Hemoglobin (< 111.2 g/L)	1.314	0.354	13.801	3.722	1.861-7.445	< 0.001
HbA1c (> 7.1%)	1.104	0.167	43.777	3.016	2.175-4.183	< 0.001
MDROs	0.946	0.344	7.547	2.575	1.311-5.058	0.006

CI: Confidence interval; DFU: Diabetic foot ulcer; HbA1c: Glycated hemoglobin; MDRO: Multidrug-resistant organism; OR: Odds ratio.

ROC curves were constructed for age, serum albumin, hemoglobin, and HbA1c, yielding areas under the curve values of 0.6302, 0.6247, 0.6490, and 0.7947, respectively (Figure 2).

Figure 2 Receiver operating characteristic curves of the logistic model. A: Age; B: Serum albumin; C: Hemoglobin; D: Glycated hemoglobin. AUC: Area under the curve.

Comparison of outcomes

No significant differences were observed between the groups in terms of lower-limb or toe amputation or in-hospital mortality (P > 0.05). However, compared with the non-malnutrition group, patients in the malnutrition group had a longer mean hospital stay (20.6 ± 7.0 days vs 19.0 ± 4.7 days, P = 0.029) and a lower rate of wound healing within 60 days (24.0% vs 40.1%, P = 0.008; Table 4).

Table 4 Comparison of outcomes between the two groups, mean ± SD/n (%).

	Malnutrition group (n = 96)	Non-malnutrition group (n = 172)	P value
Amputation	5 (5.2)	4 (2.3)	0.209
Hospital stays (days)	20.6 ± 7.0	19.0 ± 4.7	0.029
In-hospital death	4 (4.2)	5 (2.9)	0.583
Wound healing within 60 days	23 (24.0)	69 (40.1)	0.008

DISCUSSION

T2DM is a metabolic disorder resulting from the combined effects of genetic, environmental, and lifestyle factors, with its core mechanism being insufficient insulin secretion or impaired insulin function. The global prevalence of T2DM has risen sharply in recent years, a trend exemplified in China, where it represents 90%-95% of the total population of patients with diabetes[2]. The lifetime incidence of DFUs among patients with diabetes is estimated to be between 15% to 25%[19]. DFUs are one of the most serious chronic complications of T2DM and the most common cause of hospitalization. DFUs lead to adverse outcomes such as non-healing ulcers, amputation, and death, severely affecting patients’ quality of life. Approximately 85% of all amputations are attributable to this complication, making it the leading cause of non-traumatic lower-limb amputation[20].

Malnutrition is a major problem among patients with T2DM. Previous studies conducted among inpatients with T2DM have shown a prevalence of protein-energy malnutrition ranging from 20.0% to 52.9%[21-23]. Thus, the prevalence of malnutrition observed in this study is consistent with prior reports. This increased risk may be partially attributed to T2DM related autonomic neuropathy, which can lead to anorexia and gastroparesis. Additionally, use of antihyperglycemic medications, along with strict dietary restrictions or consistently low energy intake to manage blood glucose levels, can further contribute to malnutrition[24].

With respect to wound healing, there are several primary aspects regarding the detrimental effects of malnutrition in patients with T2DM. First, by contributing to reductions in lymphocyte counts and impairing phagocytic function, malnutrition impairs immune defense mechanisms as both lymphocyte counts and phagocytic activities play essential roles in combating infections during the early stages of healing. Deficiencies in essential nutrients further compromise both the integrity of physical barriers and cellular immunity, thereby heightening the susceptibility of wounds to infection[25,26]. Second, T2DM also causes immune dysfunction, leading to low-grade metabolic inflammation, particularly among the elderly. In hyperglycemia, activation of the polyol and hexosamine pathways and protein kinase C, along with the production of advanced glycation end products and glycolytic intermediates, can lead to an excessive generation of reactive oxygen species and the induction of oxidative stress[27,28]. Third, malnutrition inhibits the proliferation of fibroblasts and synthesis of collagen, thereby adversely influencing the proliferative and remodeling phases[29].

The association between advanced age and impaired nutritional status is controversial. Thaenpramun et al[24], reported no association between age and poor nutritional status. However, in the present study, patients with T2DM aged over 65 years were prone to malnutrition, consistent with most reports[30,31]. This may be explained by several factors. Elderly patients with diabetes likely experience reduced appetite and difficulty maintaining a balanced diet owing to changes in taste and smell, as well as challenges with chewing and swallowing. In addition, diabetes management requires dietary control, including restrictions on sugar and highcarbohydrate foods. Overly restrictive management can lead to inadequate nutrient intake. Furthermore, the long-term effects of hyperglycemia and disease progression often result in various chronic complications in elderly patients, further increasing the risk of malnutrition.

In contrast, the risk of malnutrition was found to be inversely associated with hemoglobin, serum albumin, and HbA1c levels. In this study, low hemoglobin level (< 111.2 g/L) was identified as a risk factor for malnutrition in patients with DFUs. Anemia is defined as a deficit in red blood cells or a reduced hemoglobin concentration[32]. Malnutrition is a common etiological factor for anemia. Iron, folate, or vitamin B12 deficiencies can lead to malnutrition-related anemia, a condition frequently observed in the elderly[33]. The association between diabetes and anemia has been proven; however, the potential mechanism remains unclear[34].

A significant correlation between malnutrition and serum albumin has also been confirmed[35-37]. Hypoalbuminemia (serum albumin < 35 g/L) has traditionally been considered a standard biomarker of malnutrition[38]. However, some studies indicated that serum albumin levels did not accurately reflect nutritional status[39,40]. The study showed an association between lower serum albumin (< 36.6 g/L) and malnutrition in patients with DFUs. Low serum albumin is a strong indicator of disease-related malnutrition and is more accurately a sign of the metabolic consequences of illness.

In the present study, the association between elevated HbA1c levels (> 7.1%) and malnutrition in patients with DFUs suggests that poorly controlled diabetes increases the risk of poor nutritional status, aligning with previous findings[41,42]. Uncontrolled high blood glucose levels can impair protein metabolism and disrupt fat synthesis, thereby affecting the body’s utilization of nutrients[43]. High HbA1c levels reflect long-term poor blood glucose control and indicate persistent glucose metabolism disorders. These intensified metabolic disturbances significantly reduce the syntheses of proteins and other energy-supplying substances, which may suppress immune function and increase the risk of infection. Furthermore, chronic hyperglycemia can alter gut microbiota composition, compromising the efficiency of nutrient absorption[38]. Notably, the observed association between malnutrition and HbA1c levels contradicts some previous findings, highlighting the need for further investigation[39].

DFUs are caused by multiple factors, with ischemia and neuropathy being the two key pathological components. Infections typically occur as a secondary complication following the onset of ischemia and neuropathy. In patients with DFUs, infections usually become refractory and difficult to control. In recent years, the extensive use of broad-spectrum antibiotics has made it highly prone to induce bacterial resistance gene mutations, leading to MDROs. This increases the difficulty of infection control, especially in older patients with T2DM who are at a higher risk of MDROs owing to multiple underlying diseases and declining physiological functions. Malnutrition and infection are causally related. Malnutrition increases susceptibility to infection, and the infection itself causes malnutrition to become more severe[44].

Major protein-calorie malnutrition and specific nutrient deficiencies impair wound healing by delaying the reparative response. In this study, we also found that malnutrition increased the risk of delayed healing of DFUs, aligning with the findings of Yuan et al[15], who reported that 66.5% of DFUs patients with malnutrition failed to achieve healing within 6 months. Moreover, it showed that the presence of malnutrition increased the risk of prolonged hospitalization in this cohort. Therefore, early intervention for those high malnutritional risk patients with T2DM and DFUs is essential.

This study has some limitations. First, the retrospective, single-center design and our dependence on electronic medical records may have introduced selection bias. Although the multivariate model we used was adjusted for the available variables, owing to a lack of data, we were unable to account for important underlying confounding variables, such as other inflammatory markers. Second, the validation cohort was relatively small; therefore, the statistical power of the results obtained may have been limited.

CONCLUSION

Malnutrition is a significant and prevalent concern in hospitalized patients with DFUs and is associated with adverse clinical outcomes, such as prolonged hospitalization and impaired wound healing. To improve prognosis, early nutritional intervention is recommended for patients presenting with key risk factors, including advanced age, low serum albumin, decreased hemoglobin, elevated HbA1c, and MDROs infection.