Effects of perioperative early enteral nutrition and glycemic control in patients with diabetes mellitus complicated with gastric cancer

Abstract

BACKGROUND

Patients with type 2 diabetes mellitus (T2DM) complicated with gastric cancer (GC) may experience hyperglycemia, malnutrition, and decreased immunity perioperatively. Without timely intervention, these conditions may negatively affect patients’ postoperative recovery.

AIM

To investigate the effects of perioperative early enteral nutrition (EEN) combined with glycemic control in patients with T2DM complicated with GC.

METHODS

A total of 99 patients with T2DM complicated with GC admitted to Chinese People’s Liberation Army 964 Hospital between May 2023 and May 2025 were enrolled. Patient were grouped according to postoperative intervention regimens: The control group (n = 48) received EEN combined with standard glycemic control, whereas the research group (n = 51) received EEN combined with intensive glycemic control. Clinical data were comparatively analyzed, including glycemic parameters (e.g., fasting blood glucose, 2-hour postprandial blood glucose, and glycated hemoglobin), nutritional indicators (e.g., prealbumin, transferrin, and total protein), humoral immunity indices (immunoglobulin A/M/G), recovery indicators (e.g., wound healing time, time to first passage of flatus, and length of hospitalization), and complications (e.g., hypoglycemia, urinary infection, incision infection, and intestinal obstruction).

RESULTS

Compared with the control group, the research group showed significantly lower glycemic parameters, shorter wound healing time, time to first passage of flatus, and length of hospitalization, higher levels of prealbumin, transferrin, total protein, and humoral immunity indicators, and comparable overall incidence of complications after treatment.

CONCLUSION

Perioperative EEN combined with intensive glycemic control in patients with T2DM complicated with GC helps reduce blood glucose levels, improve nutritional and humoral immune function, and promote recovery without significantly increasing the overall risk of complications.

Key Words: Type 2 diabetes mellitus; Gastric cancer; Perioperative period; Early enteral nutrition; Glycemic control

Core Tip: This non-randomized retrospective cohort study analyzed the effects of perioperative early enteral nutrition (EEN) combined with glycemic control in patients with type 2 diabetes mellitus complicated with gastric cancer, using EEN combined with standard glycemic control serving as the control intervention. Comparative analyses demonstrated that perioperative EEN combined with intensive glycemic control was more effective than EEN combined with standard glycemic control. Specifically, the former intervention more effectively controlled blood glucose, improved nutritional status and humoral immune function, and promoted early recovery without increasing the overall incidence of complications.

INTRODUCTION

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, accounting for up to 95% of all diabetes mellitus (DM) cases[1]. Approximately 18% of patients with cancer developed T2DM, those with the condition exhibit a 42% increased risk of mortality and a 21% increased risk of recurrence[2]. Patients with gastric cancer (GC) face a 35% increased risk of developing T2DM, which is significantly associated with poorer survival outcomes[3]. This may be associated with pathological changes such as poor glycemic control, insulin resistance, and oxidative stress[4]. There is a strong bidirectional association between GC and T2DM, and the pathophysiological mechanisms underlying their comorbidity are complex[5]. Perioperatively, patients with T2DM complicated with GC often experience hyperglycemia, malnutrition, and compromised immunity due to both the underlying disease and postoperative stress responses[6]. A retrospective cohort study with propensity score matching demonstrated that DM significantly increases the risk of overall complications and prolongs postoperative recovery time in patients with GC undergoing radical surgery, suggesting that patients with T2DM complicated with GC may face higher complication risks and delayed recovery[7]. Therefore, postoperative nutritional and glycemic interventions may facilitate early recovery in these patients.

Early enteral nutrition (EEN) is an early nutritional intervention involving the sequential administration of 0.9% sodium chloride solution followed by enteral nutrition emulsion via a nasogastric tube within 24 hours postoperatively[8]. A systematic review and meta-analysis showed that EEN is more effective than early parenteral nutrition in preventing bloodstream infections and reducing gastrointestinal complications, including vomiting and diarrhea, in critically ill patients[9]. In perioperative patients with stage II-III GC, integrated problem-oriented care model interventions also facilitate nutritional improvement, recovery promotion, alleviation of anxiety and depression, and prevention of overall complications[10]. Compared with total parenteral nutrition, EEN helps maintain nutritional status and glycemic control in patients with DM complicated with GC while reducing postoperative complication risks[11]. Furthermore, blood glucose monitoring and control are crucial in patients with T2DM complicated with GC, contributing to disease remission maintenance and recurrence prevention to some extent[12]. A randomized controlled trial demonstrated that intensive glycemic control in patients with DM receiving enteral nutrition after gastrectomy was more effective than conventional control in reducing surgical site infection rates, although it may increase the risk of hypoglycemia[13]. This study primarily compared the clinical outcomes of EEN combined with standard glycemic control vs EEN combined with intensive glycemic control in patients with T2DM complicated with GC perioperatively. Given the limited existing evidence, this study’s findings may further optimize the perioperative clinical management in patients with T2DM complicated with GC.

MATERIALS AND METHODS

Case selection

Inclusion criteria were as follows: (1) Preoperative diagnosis of T2DM[14]; (2) Histopathological confirmation of stage I-III GC[15]; (3) Indication for radical GC resection; and (4) Complete clinical data. Exclusion criteria were as follows: (1) Anemia symptoms; (2) Concomitant immune system disorders or acute infections; (3) Other malignancies; (4) Psychiatric or neurological disorders or cognitive impairment; (5) Severe hepatic or renal insufficiency; and (6) Presence of surgical contraindications. A total of 99 patients with T2DM complicated with GC admitted to Chinese People’s Liberation Army 964 Hospital between May 2023 and May 2025 were screened according to the above criteria and enrolled in this study. The control group comprised 48 patients receiving EEN combined with standard glycemic control, while the research group included 51 patients receiving EEN combined with intensive glycemic control. No statistically significant differences in baseline characteristics were observed between the two groups (P > 0.05), indicating good clinical comparability.

Intervention methods

All patients received EEN as follows: A nasogastric tube was placed 24 hours postoperatively. Initially, 0.9% sodium chloride solution was administered. In the absence of abnormal gastrointestinal symptoms, enteral nutrition emulsion (TPF-D; Fresenius Kabi) was infused using a slow-to-fast drip method, starting at 500 mL/day and gradually increasing to 1500 mL/day.

Additionally, patients in the control group received standard glycemic control through intravenous infusion of insulin aspart (3 mL:300 U) perioperatively to maintain target blood glucose levels of < 11.1 mmol/L (< 200 mg/dL). Patients in the research group received intensive glycemic control via continuous subcutaneous insulin infusion using an insulin pump with insulin aspart perioperatively to maintain target blood glucose levels of 4.4-6.1 mmol/L (80-110 mg/dL). Insulin doses in both groups were individually adjusted according to blood glucose levels, dietary habits, and other relevant factors.

Data collection and outcome measures

Glycemic parameters: Fasting venous blood (3 mL) was drawn from both groups preoperatively and at 7 days postoperatively. After centrifugation, the serum was separated. Fasting blood glucose and 2-hour postprandial blood glucose levels were measured with a fully automated biochemical analyzer (Beijing MDTK Biology Technology Co., Ltd., MD-1001) using the glucose oxidase method. Glycated hemoglobin levels were determined using high-performance liquid chromatography with an automated glycated hemoglobin analyzer (Shanghai Yuduo Biotechnology Co., Ltd., V542359). A fasting state was defined as fasting for at least eight hours.

Nutritional indicators: Prealbumin (PA), transferrin (TRF), and total protein (TP) levels were measured preoperatively and at 7 days postoperatively using the enzyme-linked immunosorbent assay. The corresponding human enzyme-linked immunosorbent assay kits were purchased from Shanghai Guyan Industrial Co., Ltd. (GOY-H10832, GOY-H11396, and GOY-H11405).

Humoral immunity: Serum immunoglobulin (Ig) A/M/G levels were determined preoperatively and at 7 days postoperatively using immunoturbidimetric assay with a fully automated biochemical analyzer. The corresponding human IgA/M/G turbidimetric assay kits were purchased from Shanghai Yuduo Biotechnology Co., Ltd. (YDLC-15450, YDLC-16006, and YDLC-16002).

Recovery indicators: The wound healing time, time to first passage of flatus, and length of hospitalization were observed and recorded in both groups. Wound healing was defined as the absence of redness, swelling, exudate, splitting, or other abnormalities at the incision site, meeting primary healing criteria; duration was recorded from the date of surgery to the date of clinical determination of healing. Anal flatus was defined as the first postoperative passage of gas from the anus perceived by the patient. Length of hospitalization was defined as the actual number of hospitalized days from the date of surgery until discharge criteria were met, including stable vital signs, tolerance of oral feeding, independent activity, and adequate pain control with oral medication.

Complications: Post-treatment complications occurring before discharge, including hypoglycemia, urinary infection, incision infection, and intestinal obstruction, were observed and recorded, and the overall incidence was calculated.

Statistical analysis

Continuous variables are expressed as mean ± SD. Two groups were compared using the independent-sample t-test, while comparisons before and after treatment within the same group were analyzed using the paired t-test. Categorical variables are expressed as n (%), with two groups compared using the χ² test. Statistical analyses were performed using SPSS 22.0 software. P < 0.05 was considered statistically significant.

RESULTS

Comparative analysis of general data

Table 1 presents the general data of both groups. Comparison revealed no significant intergroup differences in sex, mean age, T2DM duration, GC staging, or type of surgery (P > 0.05).

Table 1 Comparative analysis of general data, n (%)/mean ± SD.

Data	Control group (n = 48)	Research group (n = 51)	χ2/t	P value
Gender			0.291	0.590
Male	28 (58.33)	27 (52.94)
Female	20 (41.67)	24 (47.06)
Mean age (years)	66.02 ± 6.50	63.71 ± 7.05	-	-
Duration of T2DM (years)	9.56 ± 2.67	9.94 ± 1.99	-	-
GC staging			0.438	0.803
I	14 (29.17)	17 (33.33)
II	18 (37.50)	20 (39.22)
III	16 (33.33)	14 (27.45)
Type of surgery			0.552	0.759
Gastrectomy	5 (10.42)	7 (13.73)
Distal gastrectomy	30 (62.50)	33 (64.71)
Proximal gastrectomy	13 (27.08)	11 (21.57)

T2DM: Type 2 diabetes mellitus; GC: Gastric cancer.

Comparative analysis of glycemic parameters

Glycemic parameters were compared between the two groups (Figure 1). No significant intergroup differences in fasting blood glucose, 2-hour postprandial blood glucose, or glycated hemoglobin were observed before treatment (P > 0.05). At 7 days after treatment, all glycemic parameters were significantly reduced in both groups (P < 0.05), with more profound reductions in the research group (P < 0.05).

Figure 1 Comparative analysis of glycemic parameters. ^aP < 0.05 vs before treatment; ^bP < 0.01 vs before treatment; ^cP < 0.05 vs the control group. A: Pre-treatment and post-treatment fasting blood glucose in the control group and the research group; B: Pre-treatment and post-treatment 2-hour postprandial blood glucose in the control group and the research group; C: Pre-treatment and post-treatment glycated hemoglobin in the control group and the research group. FBG: Fasting blood glucose; 2h-PBG: 2-hour postprandial blood glucose; HbA1c: Glycated hemoglobin.

Comparative analysis of nutritional indicators

Figure 2 presents the nutritional indicators of both groups. No significant intergroup differences in PA, TRF, or TP were observed before treatment (P > 0.05). At 7 days after treatment, all nutritional indicators in the control group were significantly reduced (P < 0.05). In the research group, PA and TRF were significantly reduced, whereas TP was significantly increased at 7 days after treatment (P < 0.05). Furthermore, the research group demonstrated higher PA, TRF, and TP levels than the control group (P < 0.05).

Figure 2 Comparative analysis of nutritional indicators. ^aP < 0.05 vs before treatment; ^bP < 0.01 vs before treatment; ^cP < 0.05 vs the control group. A: Pre-treatment and post-treatment prealbumin in the control group and the research group; B: Pre-treatment and post-treatment transferrin in the control group and the research group; C: Pre-treatment and post-treatment total protein in the control group and the research group. PA: Prealbumin; TRF: Transferrin; TP: Total protein.

Comparative analysis of humoral immunity

Figure 3 shows the evaluation of humoral immunity indicators in both groups. No significant intergroup differences in IgA/IgM/IgG levels were observed before treatment (P > 0.05). After treatment, all humoral immunity indicators increased significantly in both groups (P < 0.05). At 7 days after treatment, the research group exhibited higher levels of all humoral immunity indicators than the control group (P < 0.05).

Figure 3 Comparative analysis of humoral immunity indicators. ^aP < 0.05 vs before treatment; ^bP < 0.01 vs before treatment; ^cP < 0.05 vs the control group. A: Pre-treatment and post-treatment immunoglobulin (Ig) A in the control group and the research group; B: Pre-treatment and post-treatment IgM in the control group and the research group; C: Pre-treatment and post-treatment IgG in the control group and the research group. Ig: Immunoglobulin.

Comparative analysis of recovery indicators

Comparative analysis of recovery indicators is shown in Figure 4. Compared with the control group, the research group demonstrated significantly shorter wound healing time, time to first passage of flatus, and length of hospitalization (P < 0.01).

Figure 4 Comparative analysis of recovery indicators. ^bP < 0.01. A: Wound healing time in the control group and the research group; B: Time to first passage of flatus in the control group and the research group; C: Length of hospital stay in the control group and the research group.

Comparative analysis of complications

The incidence of complications is shown in Table 2. No significant difference in the overall incidence of complications, including hypoglycemia, urinary infections, incision infections, and intestinal obstruction, was observed between the two groups (P = 0.202).

Table 2 Comparative analysis of complications, n (%).

Complication	Control group (n = 48)	Research group (n = 51)	χ2	P value
Hypoglycemia	3 (6.25)	2 (3.92)	-	-
Urinary infection	2 (4.17)	1 (1.96)	-	-
Incision infection	2 (4.17)	1 (1.96)	-	-
Ileus	2 (4.17)	1 (1.96)	-	-
Total	9 (18.75)	5 (9.80)	1.630	0.202

DISCUSSION

Numerous studies have shown that patients with T2DM have a higher risk of developing GC. The complex interplay of factors, including high salt intake, obesity, insulin resistance, hyperglycemia, hyperinsulinemia, and Helicobacter pylori infection, may contribute to the association between these two conditions[16]. Patients with T2DM complicated with GC often exhibit more severe hyperglycemic symptoms, leading to progressive glucose intolerance that may increase complication risk and hinder optimal therapeutic outcomes and postoperative recovery[17]. This study demonstrated that EEN combined with intensive glycemic control was more effective in reducing blood glucose levels in patients with T2DM complicated with GC. These effects may be attributed to the precise and stable glycemic regulation achieved through continuous subcutaneous insulin infusion via an insulin pump, which helps avoid dose fluctuations and interruptions associated with intravenous infusion[18]. Additionally, EEN combined with intensive glycemic control significantly improved nutritional indicators and overall nutritional status in these patients. This improvement may be associated with the optimized metabolic environment achieved under intensive glycemic control, which facilitates the establishment of a favorable anabolic state for protein synthesis[19].

Humoral immunity assessment further revealed that EEN combined with intensive glycemic control improved humoral immune function in patients with T2DM complicated with GC at 7 days after treatment. The significant improvement in nutritional status achieved through intensive glycemic control may contribute to this enhancement. Moreover, intensive glucose control may also help alleviate immune suppression[20]. Postoperative recovery assessments showed that EEN combined with intensive glycemic control significantly shortened wound healing time, time to first passage of flatus, and length of hospitalization in patients with T2DM complicated with GC, proving clinical advantages in promoting early recovery. Hyperglycemia suppresses the proliferation and migration of fibroblasts and epithelial cells, whereas intensive glycemic control helps restore these cellular functions and thereby promote wound healing. Additionally, EEN intervention aids in repairing the intestinal mucosal barrier and promoting gastrointestinal hormone secretion, thereby facilitating gastrointestinal function recovery in patients with T2DM complicated with GC[21,22]. The shortened hospitalization observed in these patients may therefore reflect the combined clinical benefits of improved glycemic control, enhanced nutritional status, and strengthened humoral immune function. Regarding safety, EEN combined with intensive glycemic control did not significantly increase the overall incidence of complications, including hypoglycemia, urinary infections, incision infections, and intestinal obstruction, suggesting a favorable safety profile. The continuous microinfusion mode of insulin pumps may cause fewer severe blood glucose fluctuations than high-dose intravenous administration, thereby reducing hypoglycemic events to some extent[23]. Additionally, intensive glycemic control helps enhance humoral immune function, thereby preventing urinary and wound infections[24,25].

This study has several limitations. First, the sample size was relatively small, and future studies with larger sample sizes are needed to improve accuracy and generalizability of the results. Second, due to the retrospective nature of the study, detailed clinical records regarding complication severity were limited, precluding Clavien-Dindo classification analysis. Future prospective studies should incorporate this classification system to improve result comparability. Third, the observation endpoint for blood glucose, nutritional status, and immune markers was limited to 7 days postoperatively, and longer-term metabolic and functional recovery outcomes (e.g., 30 days or 90 days postoperatively) were not evaluated. Future studies should prospectively include long-term follow-up assessments to clarify the sustained efficacy of perioperative EEN combined with intensive glycemic control.

CONCLUSION

In conclusion, perioperative EEN combined with intensive glycemic control in patients with T2DM complicated with GC helps alleviate hyperglycemia, improve nutritional status and humoral immune function, promote early recovery, and maintain clinical safety.