Invest Clin 66(1): 89 - 100, 2025 https://doi.org/10.54817/IC.v66n1a08

Corresponding author: Long Ling, Department of Metabolic Endocrinology, The Second Affiliated Hospital of Gui-

zhou University of Traditional Chinese Medicine, Guiyang 550000, Guizhou, China. E-mail: LLYLHD358@163.com

Effect of early enteral nutrition

on postoperative outcomes in pancreatic

cancer patients with diabetes.

Xinjie Wang1, Xianglong Wang1, Yang Zhang1, Zhenyang Wang1, Ying Jiang1 and Long Ling2

1Department of Hepatobiliary Surgery, The First Affiliated Hospital of Guizhou

University of traditional Chinese medicine, Guiyang, Guizhou, China.

2Department of Metabolic Endocrinology, The Second Affiliated Hospital of Guizhou

University of traditional Chinese medicine, Guiyang, Guizhou, China.

Keywords: diabetes mellitus; early enteral nutrition; gastrointestinal function;

pancreatic cancer.

Abstract. This study aimed to evaluate the impact of early enteral nutri-

tion support in pancreatic cancer patients with diabetes mellitus following to-

tal pancreatectomy. Ninety-six patients were randomly divided into control and

research groups, each with 48 patients. Both groups received parenteral nutri-

tion, while the research group received additional enteral nutrition within the

first 48 hours post-surgery. Results showed that the research group experienced

faster recovery of bowel sounds, earlier first defecation, and shorter gastric

tube retention times compared to the control group (p<0.05). Postoperative

gastrointestinal function, immune function, and nutritional status were signifi-

cantly better in the research group, with higher levels of gastrin, motilin, im-

munoglobulins G, A, and M, CD4/CD8 ratio, albumin, prealbumin, and trans-

ferrin (p<0.05). Furthermore, the research group had better blood glucose

control from 48 hours to seven days post-surgery (p<0.05). The above results

demonstrated a promoting impact of early nutrition support on postoperative

physical functioning recovery of pancreatic cancer patients with diabetes melli-

tus. In conclusion, early enteral nutrition support in pancreatic cancer patients

with diabetes mellitus significantly improved nutritional status, postoperative

gastrointestinal recovery, gastrointestinal and immune function, and blood glu-

cose control, leading to a better overall prognosis.

90 Wang et al.

Investigación Clínica 66(1): 2025

Efecto de la nutrición enteral temprana en los resultados

postoperatorios en pacientes con cáncer de páncreas

y diabetes.

Invest Clin 2025; 66 (1): 89 – 100

Palabras clave: diabetes mellitus; nutrición enteral temprana; función gastrointestinal;

cáncer de páncreas.

Resumen. Este estudio tuvo como objetivo evaluar el impacto del apoyo

nutricional enteral temprano en pacientes con cáncer de páncreas y diabetes

mellitus después de una pancreatectomía total. Noventa y seis pacientes fueron

divididos aleatoriamente en grupos de control y de investigación, cada uno con

48 pacientes. Ambos grupos recibieron nutrición parenteral, mientras que el

grupo de investigación recibió nutrición enteral adicional dentro de las prime-

ras 48 horas posteriores a la cirugía. Los resultados mostraron que el grupo

de investigación experimentó una recuperación más rápida de los ruidos in-

testinales, una primera defecación más temprana y tiempos de retención del

tubo gástrico más cortos en comparación con el grupo de control (p<0,05).

La función gastrointestinal posoperatoria, la función inmunológica y el estado

nutricional fueron significativamente mejores en el grupo de investigación, con

niveles más altos de gastrina, motilina, inmunoglobulinas G, A y M, relación

CD4/CD8, albúmina, prealbúmina y transferrina (p<0,05). Además, el grupo

de investigación tuvo un mejor control de la glucemia desde las 48 horas has-

ta los siete días posteriores a la cirugía (p<0,05). Los resultados anteriores

demostraron un efecto promotor del apoyo nutricional temprano en la recupe-

ración de la función física posoperatoria de pacientes con cáncer de páncreas

y diabetes mellitus. En conclusión, el apoyo nutricional enteral temprano en

pacientes con cáncer de páncreas y diabetes mellitus mejoró significativamente

el estado nutricional, la recuperación gastrointestinal posoperatoria, la función

gastrointestinal e inmunitaria y el control de la glucemia, lo que condujo a un

mejor pronóstico general.

Received: 16-12-2024 Accepted: 27-02-2025

INTRODUCTION

As a common malignancy, pancreatic

cancer (PC) majorly occurs in the exocrine

glands of patients’ pancreas 1,2 we assessed

serum trace element concentrations in pa-

tients with pancreatic cancer and compared

the results to those of healthy controls and

patients with chronic pancreatitis. We evalu-

ated the association between trace element

concentrations during cancer treatment and

the risk of cancer progression and mortal-

ity in pancreatic cancer patients. Methods A

retrospective cohort study was conducted at

a tertiary center in Korea. Serum trace ele-

ment concentrations of cobalt (Co. Gener-

ally, PC develop pretty rapidly, and patients’

prognosis is unfavorable, with high morbid-

ity and mortality in China. Moreover, PC has

become a common disease that endangers

Enteral nutrition on patients with pancreatic cancer and diabetes 91

Vol. 66(1): 89 - 100, 2025

the health of the body and the quality of

daily life 3,4 consequently raising the pancre-

atic cancer surgery rate. This study aimed

to determine whether advanced age is a risk

factor for morbidity and mortality following

pancreaticoduodenectomy (PD. Diabetes

mellitus (DM) is a metabolic disease result-

ing from insulin secretion or use defects 5.

Once it co-occurs with PC, it can enhance

the severity and complexity of the disease

and bring severe consequences to patients 6.

Currently, surgery is usually used to

treat pancreatic cancer, which can effectively

clear focus, prevent metastasis of focus, and

prolong the survival period of patients. Total

pancreatectomy refers to reconstruction and

anastomosis of the digestive tract after re-

moving the entire pancreas, duodenum, a sig-

nificant part of the stomach, lower segment

of common bile duct, gallbladder, large and

small omentum and spleen 7. PC patients suf-

fer from malnutrition and poor immune func-

tion, and surgical trauma can put patients

in a state of stress and immunosuppression;

thus, their nutritional status and immune

function will further deteriorate 8,9 due to the

complexity of nutrition assessment, only 30-

60% of patients with nutritional risks receive

nutritional treatment at present. It is impor-

tant to identify biomarkers that may be used

to improve management of PDAC-associated

malnutrition. Serum insulin-like growth fac-

tor binding protein 2 (IGFBP2. Enteral nutri-

tion (EN) and parenteral nutrition (PN) are

fundamental nutritional methods for postop-

erative PC patients 10. Early EN has received

wide recognition in clinical practice; early ad-

ministration of nutrients in the gastrointesti-

nal tract after surgery can stimulate intesti-

nal peristalsis and related cytokine secretion,

which helps protect intestinal mucosal bar-

rier function 11. Due to the loss of pancreatic

endocrine and exocrine function in patients

after total pancreatectomy, severe glucose

metabolism disorders occur; coupled with

surgical trauma stress, blood glucose control

has become a crucial issue worthy of medi-

cal attention 12. Clinical research demon-

strates that for PC patients with DM, timely

and reasonable nutrition support in the early

postoperative period can ameliorate insulin

tolerance, facilitate reasonable blood glucose

control, and elevate postoperative recovery 13.

This research aimed to elucidate the

clinical influence of early EN support in

treating PC complicated with DM in terms

of nutritional status, postoperative gastro-

intestinal recovery, gastrointestinal and im-

mune function, and blood glucose control,

which may provide a favorable basis for pa-

tients to recover better.

PATIENTS AND METHODS

General data

The 96 patients selected with PC who

underwent total pancreatectomy in our hos-

pital from January 2021 to May 2023 were

randomly divided into a control group (CG)

and a research group (RG), with 48 cases

each. Inclusion criteria: 1) Primary PC con-

firmed by pathological examination; 2) age

ranging 18-80 years old; 3) meeting surgi-

cal indications for total pancreatectomy and

undergoing surgery under general anesthe-

sia; 4) research subjects were informed and

agreed to surgical, anesthesia, nursing, and

blood glucose control plans, and signed in-

formed consent. Exclusion criteria: 1) DM

patients (type 1 and type 2); 2) those com-

plicated with severe organic diseases such as

heart, lung, liver, and kidney; 3) those com-

plicated with primary malignancies of other

organs and systems; 4) pregnant or lactating

women; 5) those with severe postoperative

biliary and abdominal inflammation. The re-

search received approval from our hospital’s

ethics committee.

Methods

Both groups received conventional

nursing. Postoperative conventional nurs-

ing included vital sign monitoring, assisted

sputum drainage, oral nursing, skin nursing,

drainage nursing, and parenteral nutrition

92 Wang et al.

Investigación Clínica 66(1): 2025

(PN). On the day after surgery, both groups

received PN support via intravenous route,

with a total calorie intake of approximately

110 kj/(kg • d). Administered enteral nu-

trition through the NJT (nasojejunal tube)

from the second day after surgery, with an

initial volume of 500 mL (1 Kcal/mL, pro-

tein 4.5 g/100 mL, carbohydrate 14.3 g/100

mL, lipid 2.8 g/100 mL). Both groups re-

ceived conventional blood glucose monitor-

ing and blood glucose control.

The RG received an enteral nutrition

(EN) solution to prevent infection and cor-

rect electrolyte balance. Patients were given

normal saline via a nasogastric tube two days

after surgery. The nursing staff observed pa-

tients’ reactions and continued to provide in-

fusion if there was no abdominal discomfort.

Three days after surgery, patients received

Enteral Nutrition Suspension total protein-

medium chain triglycerides (TP-MCT) via a

nasogastric tube, with a dose gradually in-

creasing from 250 mL. Nursing staff con-

trolled the amount of nutrient solution used

between 1000-1500 mL/d based on the

patient’s condition. The EN supply was re-

duced gradually after patients returned to a

regular diet.

Observation indicators

1. Nutritional status: The serum albumin

(ALB), prealbumin (PA), and transfe-

rrin (TF) levels between both groups

before and seven days after surgery

were compared.

2. Postoperative recovery: The bowel

sound recovery time, anus exhaust

time, defecation time, and gastric tube

retention time between both groups af-

ter surgery received comparison.

3. Gastrointestinal function: A 5 mL ve-

nous blood sample was extracted from

both groups at dawn before and seven

days after surgery. The levels of gastrin

(GAS) and motilin (MTL) were detec-

ted with radioimmunoassay.

4. Immune function: A 5 mL venous

blood sample was extracted from both

groups at dawn before and seven days

after surgery. The serum immunoglo-

bulin G (IgG), serum immunoglobulin

A (IgA), and serum immunoglobulin

M (IgM) levels were detected with im-

munoturbidimetry. Before and seven

days after surgery, 5 mL of peripheral

venous blood was extracted from both

groups at dawn. The ratio of CD4+ cells

to CD8+ cells (CD4/CD8) was detected

with flow cytometry.

5. Blood glucose level: The fasting blood

glucose (FBG) levels in both groups be-

fore surgery, 12 h, 24 h, 36 h, 48 h, 72

h, five days and seven days after surgery

were compared.

Statistical analysis

The IBM® SPSS® 27.0 software was

used for analyzing data. Quantitative data

following a normal distribution received

expression as mean ± standard deviation

(mean ± SD), followed by t-tests for inter-

group comparisons. Counting data received

expression in percentages (%), followed by χ2

test for intergroup comparisons, p<0.05 in-

dicated a statistically significant difference.

RESULTS

General data shows no differences

between the control group and the

research group

RG: 24 males and 24 females; mean age

of 56.30 ± 6.20 years old; body mass index

(BMI): 23.10 ± 2.30 kg/m2; tumor types:

27 cases of total pancreatic cancer, and 21

cases of pancreatic head cancer invading

the pancreatic body. CG: 28 males and 20

females; mean age of 55.00 ± 6.70 years old;

BMI: 23.30 ± 2.00 kg/m2; tumor types: 30

cases of total pancreatic cancer and 18 cases

of pancreatic head cancer invading the pan-

creatic body. Both groups exhibited no sta-

tistical significance in general data (p>0.05;

Table 1).

Enteral nutrition on patients with pancreatic cancer and diabetes 93

Vol. 66(1): 89 - 100, 2025

Enteral nutrition ameliorates nutritional

status in the research group

Before surgery, there were no statisti-

cally significant differences in ALB, PA, and

TF levels between both groups (p>0.05);

seven days after surgery, ALB, PA, and TF lev-

els in both groups were elevated relative to

those in the same group before surgery; and

ALB, PA, and TF levels in the RG were elevat-

ed relative to those in CG during the same

period, indicating statistical significance (p

<0.05; Fig. 1).

Enteral nutrition accelerates

postoperative gastrointestinal recovery in

the research group

The bowel sound recovery time, anus

exhaust time, defecation time, and gastric

tube retention time in RG exhibited deple-

tion relative to those in CG, indicating sta-

tistical significance (p<0.05; Fig. 2).

Enteral nutrition enhances

gastrointestinal function in the research

group

Before surgery, there was no statistical

significance in GAS and MTL levels between

both groups (p>0.05); seven days after sur-

gery, GAS and MTL levels in both groups

exhibited elevation relative to those in the

same group before surgery, and GAS and

MTL levels in RG exhibited elevation rela-

tive to those in CG during the same period,

indicating statistical significance (p<0.05;

Fig. 3).

Enteral nutrition enhances immune

function in the research group

Before surgery, there was no statisti-

cal significance in IgG, IgA, IgM, and CD4/

CD8 levels between both groups (p > 0.05);

seven days after surgery, IgG, IgA, IgM, and

CD4/CD8 levels in both groups exhibited el-

evation relative to those in the same group

before surgery, and IgG, IgA, IgM, and CD4/

CD8 levels in RG exhibited elevation rela-

tive to those in CG during the same period,

indicating statistical significance (p<0.05;

Fig. 4).

Enteral nutrition attenuates fasting blood

glucose levels in the research group

Before surgery and 12-24 h after sur-

gery, there were no statistically significant

differences in FBG levels exhibited between

SG and CG during the same period (p<

0.05); 48 h to seven d after surgery, FBG

level in RG exhibited depletion relative to

that in CG during the same period, indicat-

ing statistical significance (p<0.05; Fig. 5).

Table 1

General data in both groups.

Groups N Gender [n (%)] Age (years) BMI (kg/m2) Tumor types [n (%)]

Male Female

Total

pancreatic

cancer

Pancreatic head

cancer invading

pancreatic body

CG 48 24 (50.00) 24 (50.00) 56.30±6.20* 23.10±2.30* 27 (56.25) 21 (43.75)

RG 48 28 (58.33) 20 (41.67) 55.00±6.70* 23.30±2.00* 30 (62.50) 18 (37.50)

χ2/t0.671 0.167 1.047 0.389

p0.413 0.868 0.298 0.533

Abbreviations: CG = Control Group; RG = Research Group; BMI = Body Mass Index; * mean ± standard deviation.

χ² test was used for categorical variables (gender, tumor types), while an independent-samples t -test was used for

continuous variables (age, BMI).

94 Wang et al.

Investigación Clínica 66(1): 2025

Fig. 1. Nutritional indicators in both groups.

RG versus CG, ns = no significance, ***p<0.05. CG = Control Group; RG = Research Group.

Values are mean ± SD. Statistical analyses were conducted using paired t-tests for within-group comparisons

and independent-sample t-tests for between-group comparisons. Abbreviations: ALB: Serum Albu-

min, PA: Prealbumin, TF: Transferrin.

Fig. 2 Postoperative recovery indicators between both groups.

RG versus CG, RG = Research Group; CG = Control Group. ****p<0.05.

Values are mean ± SD. All statistical analyses were performed using Mann-Whitney U tests because of the

non-normal distribution of the data.

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period Time period

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period

Enteral nutrition on patients with pancreatic cancer and diabetes 95

Vol. 66(1): 89 - 100, 2025

Fig. 3. Gastrointestinal function indicators in both groups.

RG versus CG, RG = Research Group; CG = Control Group. ns = no significance, ***p<0.05.

Values are expressed as mean ± SD. Statistical analyses were conducted using paired t -tests for within-group

comparisons and independent-sample t-tests for between-group comparisons. Abbreviations: GAS:

Gastrin, MTL: Motilin.

Fig. 4. Immune function indicators in both groups.

RG versus CG, RG = Research Group; CG = Control Group. ns = no significance, ***p<0.05.

All values are shown as mean ± SD. Statistical analyses were conducted using paired t-tests for within-group

comparisons and independent-sample t-tests for between-group comparisons.

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period

Before surgery

7 d after surgery

Before surgery

7 d after surgery

Time period

96 Wang et al.

Investigación Clínica 66(1): 2025

DISCUSSION

PC is a common digestive system ma-

lignancy, and total pancreatectomy is the

most effective treatment for early PC 14.

Nevertheless, due to the complexity of radi-

cal resection of PC, which involves resec-

tion of multiple organs and reconstruction

of the digestive tract, it will cause more

serious injuries to patients, and the risk of

postoperative complications for patients is

high, which may affect life safety in severe

cases 15. Thus, it is particularly crucial to

implement effective postoperative nutri-

tional treatment for PC patients undergo-

ing total pancreatectomy.

All life activities and physical functions

of living organisms are inseparable from the

support of amino acids. The crucial physio-

logical active substances in the human body,

including enzymes, hormones, antibodies,

and others, are proteins. Lack of protein can

lead to malnutrition. Serum protein levels

are the most commonly applied indicators

reflecting the nutritional status of patients,

including ALB, PA, and TF, among others 16.

Herein, after surgery, ALB, PA, and TF levels

in both groups exhibited elevation relative to

those in the same group before surgery, and

ALB, PA, and TF levels in RG were elevated

relative to those in CG during the same pe-

riod, indicating that early EN support can fa-

cilitate visceral protein synthesis and elevate

the overall nutritional status of patients. In

the study by Mękal et al. 17, which confirmed

the results of the present study, it was shown

that Early Enteral can improve the nutri-

tional status of patients after surgery. PC

patients are often accompanied by severe

gastrointestinal dysfunction, which can eas-

ily lead to malnutrition 18. Nutritional inter-

vention is one of the critical factors affect-

ing the prognosis of surgical treatment. EN

has gradually become a preferred method of

clinical nutrition due to its advantages, such

as economy, ease of maintenance, and com-

patibility with patients’ physical characteris-

tics. Early EN support can overcome PN de-

ficiency, meet patients’ early postoperative

nutritional needs, and have advantages such

as protecting the intestinal mucosal barrier,

facilitating recovery of intestinal peristalsis

function, and enhancing gastrointestinal

hormone secretion 19. In the study by ME Ha-

maker et al. 20, similar to this study, it was

shown that EN can improve the patient’s

bowel function and nutritional status. Clini-

cal reports have depicted that patients who

receive early EN after surgery have a lower

incidence of long-term related intestinal

complications, indicating that early EN after

surgery is more in line with patients’ nutri-

tional and gastrointestinal needs 21. Herein,

bowel sound recovery time, anus exhaust

time, defecation time, and gastric tube re-

tention time in RG exhibited depletion rela-

tive to those in the CG; after surgery, GAS

and MTL levels in both groups exhibited el-

evation relative to those in the same group

before surgery, and GAS and MTL levels in

RG exhibited elevation relative to those in

Fig. 5. Changes in blood glucose level in both

groups.

RG versus CG, ns = no significance, ***p<0.05.

All values are presented as mean ± SD. Repeated-

measures ANOVA and Bonferroni post hoc

tests were used for statistical analyses.

Before surgery

12 h after surgery

24 h after surgery

48 h after surgery

72 h after surgery

5 d after surgery

7 d after surgery

Time period

Fasting blood glucose level (mmol/L)

Enteral nutrition on patients with pancreatic cancer and diabetes 97

Vol. 66(1): 89 - 100, 2025

CG during the same period. This indicates

that early EN support can accelerate post-

operative recovery and ameliorate patients’

gastrointestinal function. The study by Yuan

and Xiu 22 also showed that EN can reduce

intestinal complications and problems in pa-

tients. The reasons are that early EN support

can facilitate recovery of intestinal motility

and absorption function in patients, accel-

erate organ blood circulation, improve mu-

cosal blood flow, and prevent occurrence

of mucosal acidosis and osmotic disorders;

enteral nutrients can protect integrity of

patients’ intestinal mucosa, avoid dysbiosis

of gastrointestinal microbiota, and facilitate

regeneration of intestinal mucosal cells,

enhance secretion of gastrointestinal hor-

mones, thereby elevating patients’ gastroin-

testinal function and enabling rapid recov-

ery of gastrointestinal activity 23. The study

by Chakaroun et al. 24 also showed that EN

favors the gastrointestinal microbiota and

facilitates the regeneration of intestinal mu-

cosal cells.

Due to the influence of PC itself and

the trauma of pancreatectomy, the postoper-

ative immune function of patients will be re-

duced to varying degrees, and postoperative

malnutrition will also aggravate the degree

of their immune dysfunction 25. Herein, after

surgery, IgG, IgA, IgM, and CD4/CD8 levels

in both groups exhibited elevation relative

to those in the same group before surgery,

and IgG, IgA, IgM, and CD4/CD8 levels in

RG exhibited elevation relative to those in

CG during the same period. This indicates

that early EN can enhance the immune

function of patients, may be because early

EN support can facilitate the absorption

of nutrients in the body, enhance patient’s

physical fitness, and elevate their postopera-

tive immunity; enteral nutrients can protect

damaged gastrointestinal tissue, maintain

the function of gastrointestinal microbiota,

reduce the impact of gastrointestinal micro-

biota on damaged tissue, and block occur-

rence of inflammatory responses, thereby

effectively elevating patients’ immune func-

tion 26. Negative nitrogen balance during

the perioperative period, elevated insulin

resistance due to surgical trauma, depleted

glucose absorption in peripheral tissue, and

elevated endogenous glucose production,

coupled with stress hyperglycemia due to nu-

trition, fasting, hunger, pain, and long-term

bed rest, can lead to complications such as

wound infection and delayed wound healing,

affecting patient prognosis 27. Herein, 48 h

to 7 d after surgery, FBG level in RG exhib-

ited depletion relative to that in CG during

the same period, indicating that EN inter-

vention strategies effectively elevated blood

glucose control efficacy 48 h after surgery.

The study by Liu et al. (2025) 28 also showed

that Early Enteral can improve immune sys-

tem strengthening and blood sugar control.

Thus, based on PN, combined with EN, im-

proving short-term prognosis is vital.

Early postoperative EN support for PC

patients complicated with DM can elevate

the nutritional status of patients after sur-

gery, speed up the recovery of patients, im-

prove their gastrointestinal function and

immune function, and facilitate more rea-

sonable blood glucose control, which is con-

ducive to a better prognosis of patients. The

clinical application effect is significant.

Conflict of interest

The authors declare no conflict of in-

terest.

Founding

None

Author’s ORCID numbers

• Xinjie Wang (XW):

0000-0001-5359-1164

• Xianglong Wang (XLW):

0000-0002-3283-5606

• Yang Zhang (YZ):

0000-0003-4313-110X

• Zhenyang Wang (ZW):

0009-0004-7980-1800

98 Wang et al.

Investigación Clínica 66(1): 2025

• Ying Jiang (JJ):

0000-0002-5703-4653

• Long Ling (LL):

0000-0001-6968-5800

Authors’ Participation

All authors participated in this study;

XW, XLW: Contributed to the conception of

the work, data collection, conducting the

study, and data analysis. YZ, ZW: Contributed

to the conception of the work, conducting

the study, revising the draft, and approving

the final version of the manuscript. YJ, LL:

manuscript writing, translation and editing.

Final approval of the manuscript.

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