Clinical, epidemiological, and molecular studies provide compelling evidence that most colorectal cancers arise from adenomas. The epidemiology of adenomas closely resembles that of colorectal cancer itself, and prevention of adenomas will most likely prevent colorectal cancer. Insulin resistance and type 2 diabetes are emerging as significant risk factors for colorectal (CRC) cancer and adenomas. Insulin resistance is defined as impaired biological response to the action of insulin. It is characterized by compensatory hyperinsulinemia and is associated with increased risk for Type 2 diabetes. C-peptide, a marker of insulin production, is elevated in IR and is also a risk factor for CRC. Both insulin resistance and colorectal cancer are increasingly recognized as chronic, low-level, inflammatory states. C-reactive protein (CRP), an acute phase protein and a sensitive marker of sub-clinical inflammation, is a risk factor for both IR and CRC. The Polyp Prevention Trial (PPT) was a four year large multi-center, randomized trial of 1905 participants who had a colorectal adenoma removed within six months prior to randomization. There was no effect of a comprehensive dietary intervention -counseling of patients and assignment to a diet low in fat and high in fiber, fruits, and vegetables -on the recurrence of colorectal adenomas. In a post trial analysis of the data, legume consumption was significantly associated with both adenoma recurrence and advanced adenoma recurrence. Legumes are a rich source of fermentable dietary fibers which are precursors of luminal butyrate, a compound with anti-inflammatory and anti-neoplastic properties. In addition, legumes have a low glycemic index (GI). GI is defined as the incremental area under the blood glucose curve induced by a specific carbohydrate-containing food. A limited number of epidemiologic studies show a low GI diet is associated with a reduced risk of CRC, and decreased serum CRP.We are evaluating the effects of a legume enriched, low glycemic index, high fermentable fiber diet, on CRP, (a measure of inflammation) and C-peptide (a measure of insulin resistance) in participants with four possible combinations of the risk factors insulin resistance and history of adenomatous polyps. In a randomized crossover design controlled feeding study each participant will consume the above experimental diet and a control diet for four weeks with a two week washout period between diets. We will recruit and randomize a total of 68 male participants in each of the four groups (17 each): 1. previous history of adenomas and IR; 2. previous history of adenomas without IR; 3. IR with no history of adenomas; and 4. non-IR and no history of adenomas. A secondary objective is to assess whether these endpoints change by IR status or a history of adenomas. In addition, potential fecal markers of CRC risk will be measured to assess changes in gastrointestinal inflammation, including mRNA from exfoliated fecal colonocytes. To our knowledge this is the first controlled feeding study: 1. to examine the effects of legumes or a low GI diet on markers of inflammation; 2. to compare the effects of a dietary intervention on patients with a history of colon adenomas with or without IR; and 3. to measure the effects of dietary changes in human intestinal gene expression profiles using exfoliated colonocytes.
| Flood, A; Mai, V; Pfeiffer, R et al. (2008) The effects of a high-fruit and -vegetable, high-fiber, low-fat dietary intervention on serum concentrations of insulin, glucose, IGF-I and IGFBP-3. Eur J Clin Nutr 62:186-96 |
