Skeletal Muscle Wasting and Insulin Resistance Following Surgical Stress

NCT01134809 | Completed DMC

• 1 other identifier: 09106
• Study Type: observational
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Skeletal muscle wasting or decrease in muscle mass occurs as a result of alteration in the body's mechanisms to make or break muscle protein. In animal models, the pathway termed as 'ubiquitin-proteasome pathway' (UPP) is primarily responsible for the regulation of skeletal muscle protein loss in wasting conditions and during infection(sepsis). Skeletal muscle wasting is noticed in patients having major surgery due to the inflammatory reaction triggered by special group of proteins called cytokines (inflammatory proteins), resulting in reduced muscle strength, impaired capacity to fight infections, change in bowel function, increased clinical complications and prolonged recovery. Major surgery also leads to decreased sensitivity to hormone known as insulin, resulting in 'diabeteslike'state. We hypothesize that susceptibility of patients undergoing major abdominal surgery, to skeletal muscle wasting and insulin resistance, is determined by stress response to surgery over time, leading to changes in the pathways that make or break muscle protein, namely the Akt/Foxo signalling and UPP. Therefore, the aim of this study is to establish the underlying mechanisms of skeletal muscle wasting and insulin resistance in patients undergoing major abdominal surgery.

Conditions

Insulin Resistance

Keywords

Major abdominal surgery

Outcome Measures

Primary Outcomes (1)

• postoperative insulin resistance

  First week following surgery

Study Arms (1)

Major abdominal surgery

Patients having major abdominal surgery

Procedure: Major abdominal surgery

Interventions

Major abdominal surgery PROCEDURE

All adult patients having major abdominal surgery

Major abdominal surgery

Eligibility Criteria

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

Study Population

All adult patients having major abdominal surgery

You may qualify if:

• All adult patients undergoing major open elective gastrointestinal surgery lasting 3 hours or more will be eligible for the study.

You may not qualify if:

• Patients who are:
• undergoing emergency surgery
• suffering from chronic illness, (e.g. diabetes) or other debilitating diseases
• on long term anti-inflammatory drugs, (e.g. NSAIDS, Steroids, immunosuppressant)
• on long term antibiotics
• on statins
• on full therapeutic dose of anticoagulants, or aspirin \> 325 mg/day, clopidogrel \> 75 mg/day
• suffering from bleeding diathesis
• unable to give consent
• pregnant or breastfeeding

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

University Hospitals Nottingham Queen's Medical Centre

Nottingham, Nottingham, NG7 2UH, United Kingdom

Location

Related Publications (2)

• Atkins R, Constantin-Teodosiu D, Varadhan KK, Constantin D, Lobo DN, Greenhaff PL. Major elective abdominal surgery acutely impairs lower limb muscle pyruvate dehydrogenase complex activity and mitochondrial function. Clin Nutr. 2021 Mar;40(3):1046-1051. doi: 10.1016/j.clnu.2020.07.006. Epub 2020 Jul 14.

  PMID: 32711950 DERIVED

• Varadhan KK, Constantin-Teodosiu D, Constantin D, Greenhaff PL, Lobo DN. Inflammation-mediated muscle metabolic dysregulation local and remote to the site of major abdominal surgery. Clin Nutr. 2018 Dec;37(6 Pt A):2178-2185. doi: 10.1016/j.clnu.2017.10.020. Epub 2017 Nov 2.

  PMID: 29129636 DERIVED

MeSH Terms

Conditions

Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Dileep N Lobo, Professor

  University of Notitngham

  STUDY CHAIR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2010
• First Posted: June 2, 2010
• Study Start: May 1, 2010
• Primary Completion: May 1, 2013
• Study Completion: May 1, 2013
• Last Updated: June 9, 2015

Record last verified: 2015-06

Locations

GB (1)