Preoperative Oral Carbohydrate Loading in Patients With Type 2 Diabetes Undergoing Gastrointestinal Surgery

Enhanced recovery after surgery (ERAS) programs have progressively shifted perioperative fasting practice away from prolonged fasting toward shorter fasting intervals and the selective use of clear fluids before anesthesia. Preoperative oral carbohydrate loading has been proposed as a metabolic conditioning strategy that may reduce the catabolic effects of fasting, stimulate endogenous insulin secretion, suppress lipolysis, and attenuate the postoperative decline in insulin sensitivity. However, most supporting evidence has been generated in patients without diabetes.

Patients with type 2 diabetes mellitus have baseline insulin resistance, variable pancreatic beta-cell reserve, and altered responses to carbohydrate intake. Surgical stress, anesthesia, pain, and inflammatory responses may further increase hepatic glucose production and reduce peripheral glucose utilization, resulting in postoperative hyperglycemia and worsening insulin resistance. At the same time, prolonged fasting and perioperative changes in glucose-lowering therapy may increase the risks of hypoglycemia and glycemic variability. Therefore, the potential metabolic benefit of preoperative carbohydrate loading in patients with type 2 diabetes must be evaluated together with its effects on perioperative glycemic safety.

This study is designed as a single-center, prospective, three-arm, parallel-group randomized controlled trial in adults with type 2 diabetes undergoing elective gastrointestinal surgery. The trial will compare standard ERAS fasting and non-caloric clear-fluid management with preoperative oral carbohydrate loading. A third group receiving an approximately equivalent amount of glucose intravenously is included as a prespecified mechanistic exploratory comparator.

The principal clinical question is whether preoperative oral carbohydrate loading can attenuate early postoperative insulin resistance compared with standard ERAS fasting management. The primary confirmatory comparison is therefore between the oral carbohydrate group and the standard ERAS group. The intravenous glucose group is not the basis for the primary sample-size calculation and will mainly be used to explore whether any observed metabolic effect is related predominantly to glucose substrate provision or whether the oral gastrointestinal route may provide additional metabolic effects.

To reduce treatment-related heterogeneity, perioperative diabetes management will be standardized as much as clinically feasible. Non-insulin glucose-lowering agents will be discontinued before surgery according to the study protocol and current clinical safety requirements, and insulin-based perioperative glucose management will be used when necessary. Use of insulin, including timing, dose, route, and indication, will be carefully documented because exogenous insulin may influence the interpretation of fasting insulin-based measures of insulin resistance.

Continuous glucose monitoring will be used to characterize perioperative glucose patterns, while point-of-care glucose measurement will be used to confirm clinically important high or low glucose values and to guide treatment decisions. Continuous glucose monitoring data will be analyzed within prespecified perioperative time windows to describe glucose exposure, glycemic variability, and time spent within, above, or below the target glucose range.

Because delayed gastric emptying and aspiration are important concerns in patients with diabetes, individuals with known or suspected gastroparesis, gastric outlet obstruction, upper gastrointestinal obstruction, or other conditions associated with high aspiration risk will be excluded. Gastric antral ultrasonography will be performed before anesthesia as an additional exploratory assessment of gastric contents and aspiration-related safety.

The primary metabolic assessment will focus on insulin resistance on the first postoperative day. Additional metabolic measurements will include glucose, insulin, C-peptide, and selected markers of lipid metabolism, ketone production, and surgical stress. Repeated postoperative measurements will allow evaluation of the early postoperative metabolic trajectory. Perioperative glucose control, patient comfort, postoperative nausea and vomiting, recovery variables, length of hospital stay, postoperative complications, and predefined safety events will also be assessed.

Randomization will be performed in a 1:1:1 ratio using a variable-block randomization sequence with allocation concealment. Because the interventions are visibly different, participants and the personnel administering the interventions cannot be blinded. However, laboratory personnel, outcome assessors, gastric ultrasound assessors, and statistical analysts will remain blinded to treatment allocation whenever feasible.

The study will follow the intention-to-treat principle for the primary analysis. The primary confirmatory analysis will estimate the difference in postoperative day 1 insulin resistance between the oral carbohydrate and standard ERAS groups with prespecified adjustment for clinically relevant baseline covariates. Comparisons involving the intravenous glucose group will be interpreted as mechanistic and exploratory.

This trial is intended to provide clinically relevant evidence regarding the metabolic effectiveness and perioperative safety of preoperative oral carbohydrate loading in carefully selected patients with type 2 diabetes undergoing gastrointestinal surgery, and to help define an evidence-based approach to carbohydrate administration within ERAS pathways for this population.

• Standard ERAS Fasting and Clear-Fluid Management (Other): Participants will follow the institutional ERAS preoperative fasting protocol, including cessation of solid food at least 6 hours before anesthesia and allowance of non-caloric clear fluids according to the assigned study protocol. No carbohydrate-containing beverage will be administered before surgery.
• Oral Carbohydrate Loading (Dietary supplement): Participants will receive 400 mL of a 12.5% maltodextrin solution containing approximately 50 g of carbohydrate, administered orally approximately 2 hours before induction of anesthesia.
• Intravenous Glucose (Drug): Participants will receive 500 mL of 10% glucose solution containing approximately 50 g of glucose, administered intravenously over approximately 2 hours before induction of anesthesia.

Primary outcomes

• Postoperative Day 1 Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [Postoperative day 1]: HOMA-IR will be calculated using fasting plasma glucose and fasting serum insulin measured on the morning of postoperative day 1. HOMA-IR will be calculated as fasting plasma glucose (mmol/L) × fasting insulin (μU/mL) / 22.5. Higher values indicate greater insulin resistance.

Sex: All, ages: 18 Years to 75 Years

Inclusion Criteria:

* 1.Age 18 to 75 years, regardless of sex. 2.Diagnosis of type 2 diabetes mellitus. 3.Glycated hemoglobin (HbA1c) ≤8.0%, with preoperative fasting plasma glucose generally ≤10.0 mmol/L.

  4.Scheduled to undergo elective gastrointestinal surgery. 5.Able to wear a continuous glucose monitoring (CGM) device for at least 24 hours before surgery and willing to continue monitoring until hospital discharge or the protocol-specified time point.

  6.Able to understand the study procedures, voluntarily participate in the study, and provide written informed consent.

Exclusion Criteria:

* 1\. Known or highly suspected diabetic gastroparesis, delayed gastric emptying, gastric outlet obstruction, or upper gastrointestinal obstruction.

  2\. Severe gastroesophageal reflux disease or other conditions considered by the investigator to confer a high risk of aspiration.

  3\. Emergency surgery or other non-elective surgery for which the study intervention cannot be implemented as planned.

  4\. Type 1 diabetes mellitus, gestational diabetes mellitus, or other specific types of diabetes.

  5\. Pregnancy or breastfeeding. 6. Recent systemic glucocorticoid therapy. 7. Severe hepatic or renal dysfunction, or active severe infection. 8. Inability to comply with CGM use, cognitive or psychiatric conditions preventing completion of study assessments, or anticipated poor adherence to the study protocol.

  9\. Any other condition that, in the investigator's judgment, makes the participant unsuitable for enrollment.