1. Introduction

Postoperative wound healing remains one of the most important determinants of successful recovery after abdominal surgery. Delayed wound healing contributes to prolonged hospitalization, increased healthcare costs, patient discomfort, and higher readmission rates. Hyperglycemia impairs leukocyte function, collagen synthesis, angiogenesis, and fibroblast proliferation.

While perioperative glucose targets have been incorporated into enhanced recovery protocols, recent evidence suggests that fluctuations in blood glucose may be more harmful than isolated episodes of hyperglycemia. Glycemic variability generates oxidative stress and inflammatory responses that damage endothelial cells and impair tissue regeneration.

Experimental studies have demonstrated that oscillating glucose concentrations induce greater cellular injury than persistent hyperglycemia. Few clinical studies have evaluated the impact of perioperative glucose fluctuations on wound healing after major abdominal procedures. This study therefore investigated whether increased glycemic variability independently predicts delayed wound healing and postoperative complications.

2. Materials and Methods

2.1 Study Design

A retrospective cohort study was performed at a tertiary referral center after institutional approval.

2.2 Patient Population

Adult patients (≥18 years) undergoing elective procedures were included:

• Colorectal resection
• Gastrectomy
• Hepatectomy
• Pancreatectomy
• Small bowel resection

2.3 Exclusion Criteria

• Emergency surgery
• Minor procedures
• Pregnancy
• Chronic steroid therapy
• Missing glucose data
• Death within 30 postoperative days

2.4 Data Collection

Clinical variables included:

• Age and Sex
• BMI
• Diabetes mellitus
• Smoking history
• ASA classification
• Operative duration
• Estimated blood loss
• Surgical approach
• Albumin level

2.5 Glycemic Assessment

Blood glucose was recorded preoperatively and every 6 hours during the first 72 postoperative hours. Glycemic variability was assessed using:

• Standard deviation (SD)
• Coefficient of variation (CV)
• Mean amplitude of glycemic excursions (MAGE)

Patients were divided according to the median CV.

2.6 Outcome Measures

Primary Outcome: Delayed wound healing within 30 days.

Secondary Outcomes: Surgical site infection, hospital stay, reoperation, readmission, and overall complications.

2.7 Statistical Analysis

Continuous variables were analyzed using Student's t-test or Mann–Whitney U test. Categorical variables were compared using Chi-square testing. Independent predictors were evaluated using multivariate logistic regression. Statistical significance was defined as p<0.05.

3. Results

3.1 Baseline Characteristics

A total of 312 patients met inclusion criteria. Mean age was 61.3±12.4 years. Diabetes mellitus was present in 38%. Baseline demographic characteristics were comparable between groups.

3.2 Glycemic Variability

The median coefficient of variation was 18.5%. Patients with higher variability demonstrated higher postoperative glucose peaks, greater insulin requirements, and longer ICU observation.

3.3 Wound Healing Outcomes

Delayed wound healing occurred in:

• High GV: 38 patients (24.7%)
• Low GV: 17 patients (11.0%)

This difference was statistically significant (p < 0.001).

3.4 Surgical Site Infection & Length of Stay

SSI developed in 18.2% of the High GV group versus 8.4% of the Low GV group (p = 0.013). The median hospital stay was also significantly longer for High GV patients (10 days) compared to Low GV patients (7 days) (p = 0.002).

3.5 Multivariate Analysis

Independent predictors of delayed wound healing included:

4. Discussion

The findings indicate that perioperative glycemic variability is a stronger predictor of impaired wound healing than average glucose levels alone. Patients with greater glucose fluctuations experienced significantly higher rates of delayed wound healing, surgical site infection, and prolonged hospitalization.

Oscillating glucose concentrations are believed to induce oxidative stress through repeated activation of inflammatory pathways. This process impairs fibroblast migration, collagen deposition, and angiogenesis, all of which are essential for normal wound repair. The observed association remained significant after adjusting for diabetes, nutritional status, and operative duration.

These results support previous investigations demonstrating that stable glucose management may be more beneficial than simply maintaining acceptable mean glucose values. Continuous glucose monitoring and protocol-driven insulin therapy may reduce glucose excursions during the perioperative period.

Limitations include the retrospective design, single-center setting, and absence of continuous glucose monitoring in all participants. Prospective multicenter studies are required to establish optimal glycemic variability thresholds for surgical patients.

5. Conclusion

Perioperative glycemic variability is independently associated with delayed wound healing, increased surgical site infections, and prolonged hospitalization following major abdominal surgery. Monitoring glucose fluctuations in addition to mean glucose levels may enhance perioperative risk stratification and improve postoperative outcomes. Interventions aimed at minimizing glycemic variability should be considered in enhanced recovery protocols.

Acknowledgments: The authors acknowledge the surgical nursing staff, endocrinology team, and clinical data management unit for their support during data collection.

Conflict of Interest: The authors declare no conflict of interest.

Funding: No external funding was received for this study.

Data Availability: The datasets generated during the current study are available from the corresponding author upon reasonable request.