Koohestani N, Tran T T, Lee W, Wolever T M, Bruce W R
Department of Nutritional Sciences, University of Toronto, ON, Canada.
Nutr Cancer. 1997;29(1):69-76. doi: 10.1080/01635589709514604.
McKeown-Eyssen and Giovannucci recently proposed that the etiology of insulin resistance (IR) and colorectal cancer (CRC) are related. They suggested that diets high in fat and energy and low in complex carbohydrates and a sedentary life-style lead to IR and that the associated hyperinsulinemia, hypertriglyceridemia, and glycemia lead to increased CRC risk through the growth-promoting effect of insulin or the increased availability of energy. We reasoned that if diet affects colon carcinogenesis through its effect on IR, evidence of colon cancer promotion would be preceded by evidence of IR. To test this expectation, we compared the effects of a high-fat (HF, 59% energy) diet and a low-fat (LF, 11% energy) diet on indirect measures of IR and promotion in azoxymethane-initiated F344 rats. Promotion was assessed as growth of aberrant crypt foci (ACF) at 100 days after initiation. The HF diet increased ACF size 1.4 times (95% confidence interval = 1.30-1.58) that of the LF diet. The HF diet also led to impaired oral glucose tolerance tests measured at 4, 32, 60, and 88 days and characterized by an average increased glucose concentration of 0.78 +/- 0.17 mmol/l (p < 0.001). It also resulted in an impaired intravenous glucose tolerance test and elevated levels of serum insulin after a glucose gavage. We concluded that with this model a high-fat diet leads to evidence of IR before it is possible to demonstrate CRC promotion, thus providing support, necessary but not sufficient, for the causal hypothesis linking IR and CRC. Possible mechanisms linking diet, IR, and promotion are considered.
麦基翁 - 艾森和乔瓦努奇最近提出，胰岛素抵抗（IR）和结直肠癌（CRC）的病因相关。他们认为，高脂肪、高能量以及低复合碳水化合物的饮食和久坐不动的生活方式会导致胰岛素抵抗，而相关的高胰岛素血症、高甘油三酯血症和血糖异常会通过胰岛素的促生长作用或能量供应增加导致结直肠癌风险升高。我们推断，如果饮食通过对胰岛素抵抗的影响来影响结肠癌发生，那么在出现结肠癌促进证据之前应该先有胰岛素抵抗的证据。为了验证这一预期，我们比较了高脂肪（HF，占能量的59%）饮食和低脂肪（LF，占能量的11%）饮食对经偶氮甲烷诱导的F344大鼠胰岛素抵抗间接指标以及促进作用的影响。促进作用通过诱导后100天异常隐窝灶（ACF）的生长来评估。高脂肪饮食使ACF大小增加至低脂肪饮食的1.4倍（95%置信区间 = 1.30 - 1.58）。高脂肪饮食还导致在第4、32、60和88天测量的口服葡萄糖耐量试验受损，其特征是葡萄糖浓度平均升高0.78 +/- 0.17 mmol/l（p < 0.001）。它还导致静脉葡萄糖耐量试验受损以及葡萄糖灌胃后血清胰岛素水平升高。我们得出结论，在这个模型中，高脂肪饮食在出现结肠癌促进证据之前就导致了胰岛素抵抗的证据，从而为将胰岛素抵抗和结直肠癌联系起来的因果假说提供了必要但不充分的支持。文中还考虑了饮食、胰岛素抵抗和促进作用之间可能的机制。
