The Effect of Insulin on Protein Metabolism After Cardiac Surgery

Background: The hyperinsulinemic-normoglycaemic clamp technique is a precise method of providing insulin and glucose while maintaining normoglycemia. High-dose insulin has profound effects on glucose and protein metabolism. It has been demonstrated in coronary artery bypass graft (CABG) surgery patients that high-dose insulin causes hypoaminoacidaemia. The investigators hypothesize that the reduction of plasma amino acids (AAs) levels as seen in patients undergoing CABG surgery and receiving high-dose insulin is a consequence of an inhibition of whole body proteolysis as assessed by L-[1-13C]leucine tracer kinetics.

Objective: The present study aims to investigate the effect of high-dose insulin therapy on whole body protein, glucose and end-organ metabolism in patients undergoing CABG surgery using stable isotope tracers [6,6-2H2]glucose, L-[1-13C]-leucine and L-[2H5]phenylalanine. The changes in the metabolic-endocrine milieu will also be evaluated by plasma concentrations of glucose, lactate, free fatty acids, prealbumin, albumin, fibrinogen, insulin, glucagon, and cortisol.

Methods: With the approval of local institution's ethical committee, 30 patients scheduled for elective will be enrolled. The patients will be divided randomly into two groups. The control group will receive a standard IV insulin protocol with the aim of keeping blood glucose < 10 mmol/L. The treatment group will be administered a high dose insulin infusion of 5 mU/kg/min coupled with a variable infusion of glucose to maintain normoglycemia (4-6 mmol/L). Insulin infusion will be continued until the end of the study period approximately 8 hours after surgery. L-[1-13C]leucine and [6,6-2H2]glucose kinetics will be used to assess changes in whole body protein and glucose kinetics. Hepatic albumin synthesis will be determined by using primed continuous infusion of L-[2H5]phenylalanine. The preoperative measurements will be performed on the morning before the surgery. Postoperative studies will be conducted two hours after arrival in the intensive care unit. Tracer kinetics between the two groups will be analyzed using ANOVA for repeated measurements.

Significance: High-dose-insulin results in a significant reduction in plasma AAs in cardiac surgery. This study should address if this drop in plasma AA levels is secondary to a decrease in breakdown, an increase in synthesis or both during high-dose insulin therapy in open heart surgery.

Study Overview

• Status: Unknown
• Conditions: Cardiac Surgery
• Intervention / Treatment: Drug: Regular human insulin injection

• Study Type: Interventional
• Enrollment (Anticipated): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H3A 1A1
      • Recruiting
      • Royal Victoria Hospital, McGill University Health Centre
      • Contact: Roupen Hatzakorzian, MD; Phone Number: 31104 514 934 1934; Email: roupenhatz@hotmail.com
      • Contact: Thomas Schricker, MD PhD; Phone Number: 36057 514 934 1934; Email: thomas.schricker@mcgill.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ability to give informed consent

Exclusion Criteria:

• signs of severe malnutrition or obesity: body mass index (BMI) < 20 or > 30 kg.m-2, more than 10% involuntary body weight loss over the preceding six months, serum albumin < 35 g.L-1
• chronic liver failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control
Experimental: High-dose insulin	Drug: Regular human insulin injection; Hyperinsulinemic normoglycemic clamp from beginning of surgery until 8 hours after surgery. Humulin R 5 mU/kg/min and a variable infusion of glucose.; Other Names: Humulin R

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protein breakdown	Protein breakdown as measured by 13C leucine	Eight hours after the end of surgery

Collaborators and Investigators

• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre
• Investigators: Principal Investigator: Roupen Hatzakorzian, MD, McGill University Health Centre/Research Institute of the McGill University Health Centre

Study record dates

Study Major Dates

• Study Start: June 1, 2010
• Primary Completion (Anticipated): December 1, 2012

Study Registration Dates

• First Submitted: March 9, 2012
• First Submitted That Met QC Criteria: May 17, 2012
• First Posted (Estimate): May 18, 2012

Study Record Updates

• Last Update Posted (Estimate): May 18, 2012
• Last Update Submitted That Met QC Criteria: May 17, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: Insulin; Stress response; Protein metabolism
• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: 09-105-SDR