COLONIC RESECTION FOR CANCER AS DIABETOGENIC RISK FACTOR

Study Overview
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Brief Summary
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Colon cancer (CC) survivors have an increased risk of developing T2D. A recent study revealed that the surgical procedures per se may be causally involved. Hence, left-sided colon resections increased the risk of developing T2D. In addition, treatment with chemotherapy may play a role in the pathogenesis. Given the steadily improving survival rate after a CC diagnosis, prevention of secondary diseases such as T2D is important to improve quality of life in these patients and to reduce socioeconomic expenses. This study aims to elucidate the effect of resection of tumors located in the left part of the colon on pathophysiological intermediates, which may lead to T2D 12 months post-surgery or later. The physiological mechanism might be a changed postprandial secretion of gut hormones including glucagon-like peptide-1 (GLP-1) secreted from L-cells in the left part of the colon. The investigators will evaluate changes in primarily glucose homeostasis as well as in gastrointestinal hormones, microbiota, visceral fat accumulation and markers of low-grade inflammation etc. in CC survivors who underwent a left hemicolectomy or sigmoidectomy. Material and Methods: 60 patients will be included in this explorative clinical study. Patients will be divided into 4 groups depending on surgical procedure and treatment with chemotherapy. In the group of patients undergoing left hemicolectomy or sigmoidectomy ± treatment with chemotherapy 2 x 15 patients will be included, and in the group of patients scheduled to undergo right hemicolectomy ± treatment with chemotherapy another 2 x 15 patients will be included. During the 3 study visits (before surgery, 3-4 weeks post-surgery and 12 months post-surgery) the following tests will be performed: An oral glucose tolerance test, blood and fecal sampling, a DXA scan and an ad libitum meal test. Implications: With this study the investigators expect to obtain an insight in the pathogenesis behind the possible development of T2D in CC survivors who underwent a resection of the left part of the colon ± treatment with chemotherapy. This insight may also help scientists develop new ways of treating or preventing T2D in general.

Official Title
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COLONIC RESECTION FOR CANCER AS DIABETOGENIC RISK FACTOR - A Study of the Pathophysiological Effects of Colon Resection on Glucose Homeostasis

Conditions
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Glucose Metabolism Disorders, Colon Cancer, Surgery, Chemotherapy Effect

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria: Adult (> 18 yrs.) ASA score 1-3 Signed written informed consent Hba1c <48 mmol/mol Hemoglobin ≥ 6,5 mmol/L Exclusion Criteria: • Pregnancy Known type 1 or 2 diabetes Inflammatory bowel disease (Ulcerous colitis and Crohns' disease). Prior major abdominal surgery including bariatric surgery or colorectal resections Treatment with agents that may interfere with glucose homeostasis and or appetite or reduce the chance of successful follow-up examination Planned stoma

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in 2-hour blood glucose (OGTT) 12 months after hemicolectomy ± chemotherapy |  | 3-4 weeks and 1 year after anticancer treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in blood glucose (iAUC) and (tAUC) in response to a 3-hour OGTT |  | 3-4 weeks and 1 year after anticancer treatment | 
| Changes in hemoglobin a1c (HbA1c) |  | 3-4 weeks and 1 year after anticancer treatment | 
| Changes in fasting blood glucose levels (mmol/L) |  | 3-4 weeks and 1 year after anticancer treatment |