Tran Thien T, Gupta Neehar, Goh Tracy, Naigamwalla Dinaz, Chia Marie C, Koohestani Niloofar, Mehrotra Shruti, McKeown-Eyssen Gail, Giacca Adria, Bruce W Robert
Department of Nutritional Sciences, University of Toronto, Toronto, Ontario M5S 3E2, Canada.
Cancer Epidemiol Biomarkers Prev. 2003 Jan;12(1):47-56.
The similarity in lifestyle risk factors for the development of colorectal cancer (CRC) and type 2 diabetes suggests that there are common underlying pathogenic mechanisms. High-risk lifestyle factors may lead to insulin resistance that, through increased circulating levels of energy substrates, insulin, and insulin-like growth factor-1, may promote the development of CRC. The objective was to determine the extent to which direct and surrogate measures of insulin resistance correlate with multiplicity of aberrant crypt foci, which are putative precursors of CRC. Rats were initiated with the carcinogen azoxymethane, then fed low, intermediate, or high saturated fat diets. Metabolic parameters were assessed at 50 days and ACF at 100 days after initiation. Results indicate that CRC promotion was most strongly correlated with direct measures of insulin sensitivity as assessed with the hyperinsulinemic-euglycemic clamp (r = -0.52, P < 0.009). Practical surrogate measures of insulin resistance such as insulin levels at 180 min after an oral glucose load were strongly correlated with direct measures of insulin sensitivity (r = -0.61, P < 0.001) and with CRC promotion (r = 0.42, P = 0.044) in this animal model. Fasting levels of glucose, insulin, total insulin-like growth factor-1, nonesterified fatty acids, and triglyceride, as well as body weight and insulin sensitivity indices (such as fasting insulin resistance index, quantitative insulin sensitivity check index, homeostasis model assessment formula, insulin sensitivity index of glycemia, oral glucose insulin sensitivity, and composite insulin sensitivity index for the hepatic and peripheral tissues) were all less strongly correlated with direct measures of insulin sensitivity and all poorly correlated with CRC promotion in this animal model. These correlations do not prove causality, however, they suggest possible mechanisms linking diet, insulin resistance with its related parameters, and promotion of CRC.
结直肠癌（CRC）和2型糖尿病发生的生活方式风险因素相似，这表明存在共同的潜在致病机制。高风险生活方式因素可能导致胰岛素抵抗，通过增加能量底物、胰岛素和胰岛素样生长因子-1的循环水平，可能促进CRC的发生。目的是确定胰岛素抵抗的直接和替代指标与异常隐窝灶（CRC的假定前体）的多灶性之间的关联程度。用致癌物偶氮甲烷启动大鼠，然后分别喂食低、中、高饱和脂肪饮食。在启动后50天评估代谢参数，100天评估异常隐窝灶。结果表明，CRC的促进与用高胰岛素-正葡萄糖钳夹法评估的胰岛素敏感性直接指标相关性最强（r = -0.52，P < 0.009）。在这个动物模型中，口服葡萄糖负荷后180分钟时的胰岛素水平等胰岛素抵抗的实际替代指标与胰岛素敏感性直接指标（r = -0.61，P < 0.001）以及CRC的促进（r = 0.42，P = 0.044）密切相关。空腹血糖、胰岛素、总胰岛素样生长因子-1、非酯化脂肪酸和甘油三酯水平，以及体重和胰岛素敏感性指标（如空腹胰岛素抵抗指数、定量胰岛素敏感性检查指数、稳态模型评估公式、血糖胰岛素敏感性指数、口服葡萄糖胰岛素敏感性以及肝和外周组织的复合胰岛素敏感性指数）与胰岛素敏感性直接指标的相关性均较弱，在这个动物模型中与CRC促进的相关性也都很差。然而，这些相关性并不能证明因果关系，它们提示了饮食、胰岛素抵抗及其相关参数与CRC促进之间可能的机制。
