Modulating the Stress Response in Diabetes Mellitus Type 2 Patients Undergoing Colon Surgery

NCT02863276 | Completed DMC

• 1 other identifier: 230/09
• Study Type: interventional
• Target: 18
• Locations: 0 countries
• Sites: N/A

Brief Summary

Background Surgical injury provokes a stress response. These pathways mediated by stress hormones and cytokines cause a catabolic state. The loss of body cell mass may result in prolonged convalescence and increased morbidity. Protein catabolism after colorectal surgery is even more increased in patients with type 2 diabetes mellitus. Epidural blockade, by reducing the intensity of the catabolic response, improves substrate utilization after surgery in non-diabetic patients. This effect is even more pronounced in diabetic patients receiving amino acids. The aim of the study is to explore the effect of two different protocols to manage blood glucose control on glucose and protein metabolism in patients with type 2 diabetes mellitus undergoing colon surgery and receiving epidural analgesia and perioperative feeding with amino acids. The following hypotheses are tested:

1. 1.Tight perioperative blood glucose control with intensified insulin therapy compared to standard blood glucose control in presence of general anesthesia with epidural analgesia and amino acid infusion would reduce endogenous glucose production and leucine oxidation.
2. 2.Tight blood glucose control and perioperative infusion of amino acids induce a more positive protein balance compared to standard blood glucose control by better oxidative glucose utilization and redirecting amino acids from oxidative to synthetic pathways.

Conditions

Diabetes Mellitus Type 2; Insulin Resistance

Outcome Measures

Primary Outcomes (1)

• Postoperative protein balance (leucine) (umol/kg/h)

  Measured and calculated with a 3-hour stable isotope tracer technique with L-(1-13C)leucine and calorimetry towards the end of the 3 hour period

  Postoperative period: starting with arrival in the postoperative care unit and ending after 3 hours

Secondary Outcomes (10)

• Intraoperative protein metabolism: Rate of appearance of leucine (umol/kg/h)

  Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)

• Intraoperative protein metabolism: endogenous rate of appearance of leucine (umol/kg/h)

  Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)

• Intraoperative glucose metabolism: Endogenous rate of appearance of glucose (umol/kg/min)

  Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)

• Intraoperative glucose metabolism: Glucose clearance (ml/kg/min)

  Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)

• Postoperative protein metabolism: Rate of appearance of leucine (umol/kg/h)

  Postoperative period: starting with arrival in the postoperative care unit and ending after 3 hours

Study Arms (2)

Intensified insulin group

EXPERIMENTAL

Patients undergoing elective colorectal surgery will receive standard anesthesia including epidural analgesia and nutritional support with an intravenous amino acid solution while receiving tight blood glucose control with intensified insulin therapy (blood glucose target\<6 mmol\*l-1) via an continuous insulin infusion.

Procedure: Intensified insulin therapy

Control group

NO INTERVENTION

Patients undergoing elective colorectal surgery will receive standard anesthesia including epidural analgesia and nutritional support with an intravenous amino acid solution while receiving standard blood glucose control (blood glucose target \<10 mmol\*l-1) via subcutaneous insulin boluses

Interventions

Intensified insulin therapy PROCEDURE

Also known as: continuous insulin infusion

Intensified insulin group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients undergoing elective colorectal surgery for non-metastatic disease
• Type 2 diabetes mellitus with plasma level of glycosylated hemoglobin level (HbA(1c)) less than 10% indicating normal or moderate glycemic control
• Being capable of signing informed consent
• Accepting an epidural catheter for perioperative analgesia

You may not qualify if:

• American Society of Anesthesiologists (ASA) Physical Status classification system 4 with major cardiac disorders (severe arrhythmias, recent myocardial ischemia (MI), heart failure, uncontrolled hypertension)
• Hepatic disorders (liver failure, jaundice, metastatic disease), renal disorders (acute or chronic renal failure or on dialysis)
• Metabolic disorders (untreated hyperthyroidism, pyrexia, more than 10% weight loss over the preceding three months, plasma albumin concentration \< 35g/l)
• Anemia (hemoglobin \< 10 g/dl)
• Chemotherapy or radiotherapy during six months before surgery
• Inflammatory bowel disease or other inflammatory condition
• Pregnancy
• Previous spine surgery precluding placement of an epidural catheter.

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Insulin Resistance

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Hyperinsulinism

Study Officials

• Andrea Kopp Lugli, MD, MSc

  University Hospital, Basel, Switzerland

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 8, 2016
• First Posted: August 11, 2016
• Study Start: December 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: August 11, 2016

Record last verified: 2016-08