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

Insulin Resistance Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02863276
• Other study ID #: 230/09
• Status: Completed
• Phase: N/A
• First received: August 8, 2016
• Last updated: August 8, 2016
• Start date: December 2009
• Est. completion date: November 2010

Study information

• Verified date: August 2016
• Source: University Hospital, Basel, Switzerland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Switzerland: Ethikkommission
• Study type: Interventional

Clinical Trial 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. 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. 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.

Material and Methods A total of 20 patients with diabetes mellitus type 2 undergoing elective colorectal surgery will be admitted to the study. Patients will be randomly assigned to receive standard blood glucose control (blood glucose target <10 mmol*l-1; control group; cytotoxic T lymphocyte (CTL) group, n=8) or to receive tight blood glucose control with intensified insulin therapy (blood glucose target<6 mmol*l-1; intensified insulin group; II group, n=8). All patients will receive general anesthesia and an epidural catheter for perioperative analgesia. During surgery (intraoperative state) and immediately after surgery (postoperative state) when receiving an amino acid infusion protein and glucose kinetics will be assessed using a stable isotope technique with L-[1-13C]leucine and [6,6-2H2]glucose and circulating concentrations of glucose, glucagon, insulin and cortisol will be measured. The primary endpoints of the study will be protein balance. Sample size is set to ensure at least 80% power at a significance level of 0.05.

Description:

see information below

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2010
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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.

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus Type 2
• Diabetes Mellitus, Type 2
• Insulin Resistance

Intervention

Procedure:
• Intensified insulin therapy

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Intraoperative protein metabolism: Rate of appearance of leucine (umol/kg/h)	Measured and calculated with a 3-hour stable isotope tracer technique with L-(1-13C)leucine	Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)	No
Secondary	Intraoperative protein metabolism: endogenous rate of appearance of leucine (umol/kg/h)	Measured and calculated with a 3-hour stable isotope tracer technique with L-(1-13C)leucine	Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)	No
Secondary	Intraoperative glucose metabolism: Endogenous rate of appearance of glucose (umol/kg/min)	Measured and calculated with a 3-hour stable isotope tracer technique with D-(6,6-2H2)glucose	Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)	No
Secondary	Intraoperative glucose metabolism: Glucose clearance (ml/kg/min)	Measured and calculated with a 3-hour stable isotope tracer technique with D-(6,6-2H2)glucose and plasma glucose measurement	Intraoperative period: starting with the induction of anesthesia and ending after 3 hours (during surgery)	No
Secondary	Postoperative protein metabolism: Rate of appearance of 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	No
Secondary	Postoperative protein metabolism: Endogenous rate of appearance of 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	No
Secondary	Postoperative protein metabolism: Leucine oxidation (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	No
Secondary	Postoperative protein metabolism: Protein synthesis (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	No
Secondary	Postoperative glucose metabolism: Endogenous rate of appearance of glucose (umol/kg/min)	Measured and calculated with a 3-hour stable isotope tracer technique with D-(6,6-2H2)glucose	Postoperative period: starting with arrival in the postoperative care unit and ending after 3 hours	No
Secondary	Postoperative glucose metabolism: Glucose clearance (ml/kg/min)	Measured and calculated with a 3-hour stable isotope tracer technique with D-(6,6-2H2)glucose and plasma glucose measurement	Postoperative period: starting with arrival in the postoperative care unit and ending after 3 hours	No