Attenuating The Post-Operative Insulin Resistance And Promoting Protein Anabolism

Attenuating The Post-Operative Insulin Resistance And Promoting Protein Anabolism In Patients Undergoing Major Lung or Abdominal Surgery

Major surgery results in a stress- induced catabolic response, marked by post-operative insulin resistance, hyperglycemia and loss of body protein, which is associated with increased morbidity, mortality and adverse outcomes. There has been a great deal of research on different approaches to optimize post-operative insulin sensitivity including hormonal and nutritional interventions, minimally invasive surgical techniques and epidural anesthesia. However, the correlation between insulin resistance and body protein loss is not well understood. Metformin is the most widely used insulin sensitizing and blood glucose-lowering drug in treatment of type 2 diabetic patients. This study will: 1) estimate the correlation between insulin resistance and body protein loss in pre-diabetic lung/colorectal resection patients; 2) investigate whether the post-operative metabolic state can be improved by the pre-operative administration of metformin; and assess the impact of metformin on surgical complications and hospital length of stay. The results of this study will provide insight into the relationship between insulin resistance and post-operative adverse events and potentially suggest a novel approach to improve outcomes using Metformin, a drug already in wide clinical use.

Inclusion Criteria:

1. Elective open anatomic lung resections: segmentectomy, lobectomy, bi-lobectomy
2. Colorectal surgery for non-metastatic disease (including right, transverse, left, sigmoid, subtotal, total, and hemicolectomy)
3. Primary or secondary lung cancer
4. At least 18 years of age with
5. HbA1c 5.7- 6.5 %
6. Not receiving any kind of glucose lowering medication.

Exclusion Criteria:

1. Already diagnosed with diabetes (Hb A1c > 6.5%)
2. Are pre-diabetic receiving glucose lowering intervention ( any glucose lowering medication)
3. Have renal or liver dysfunction (serum creatinine above 124 micromol/L in women and 133 micromol/L in men, bilirubin >50 micromol/L)
4. will undergo extended resection of adjacent organs, chest wall resections, bronchoplasty, non-anatomic lung resections
5. Will undergo Pneumonectomy
6. Non-elective operations
7. Have mental conditions (e.g. dementia, disabling orthopedic and neuromuscular disease, psychosis),
8. Have cardiac abnormalities, severe end-organ disease such as cardiac failure (New York Heart Association classes III-IV), Chronic obstructive pulmonary disease(COPD), sepsis, morbid obesity (BMI >40 kg/m2), anemia (hematocrit < 30 %, hemoglobin <100g/L albumin < 25mg/dl)
9. Have received steroids for longer than 30 days
10. Have poor English or French comprehension.