The existence of molecular links that facilitate colorectal cancer (CRC) development in the population with type 2 diabetes (T2D) is supported by substantial epidemiological evidence. This review summarizes how the systemic, metabolic and hormonal imbalances from T2D alter CRC cell metabolism, signalling and gene expression as well as their reciprocal meshing, with an overview of CRC molecular subtypes and animal models to study the diabetes-CRC cancer links. Metabolic and growth factor checkpoints ensure a physiological cell proliferation rate compatible with limited nutrient supply. Hyperinsulinaemia and hyperleptinaemia in prediabetes and excess circulating glucose and lipids in T2D overcome formidable barriers for tumour development. Increased nutrient availability favours metabolic reprogramming, alters signalling and generates mutations and epigenetic modifications through increased reactive oxygen species and oncometabolites. The reciprocal control between metabolism and hormone signalling is lost in diabetes. Excess adipose tissue at the origin of T2D unbalances adipokine (leptin/adiponectin) secretion ratios and function and disrupts the insulin/IGF axes. Leptin/adiponectin imbalances in T2D are believed to promote proliferation and invasion of CRC cancer cells and contribute to inflammation, an important component of CRC tumourigenesis. Disruption of the insulin/IGF axes in T2D targets systemic and CRC cell metabolic reprogramming, survival and proliferation. Future research to clarify the molecular diabetes-CRC links will help to prevent CRC and reduce its incidence in the diabetic population and must guide therapeutic decisions.

中文翻译：

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糖尿病对结直肠癌细胞信号传导的代谢和激素重塑。

大量流行病学证据支持存在促进 2 型糖尿病 (T2D) 人群中结直肠癌 (CRC) 发展的分子联系。本综述总结了 T2D 引起的全身性、代谢和激素失衡如何改变 CRC 细胞代谢、信号传导和基因表达以及它们的相互啮合，并概述了 CRC 分子亚型和动物模型以研究糖尿病与 CRC 癌症之间的联系。代谢和生长因子检查点确保生理细胞增殖率与有限的营养供应相适应。糖尿病前期的高胰岛素血症和高瘦素血症以及 T2D 中的过量循环葡萄糖和脂质克服了肿瘤发展的巨大障碍。增加的营养供应有利于代谢重编程，通过增加活性氧和癌代谢物来改变信号传导并产生突变和表观遗传修饰。新陈代谢和激素信号之间的相互控制在糖尿病中丧失。T2D 起源处的过多脂肪组织使脂肪因子（瘦素/脂联素）分泌比例和功能失衡，并破坏胰岛素/IGF 轴。T2D 中的瘦素/脂联素失衡被认为会促进 CRC 癌细胞的增殖和侵袭，并导致炎症，这是 CRC 肿瘤发生的重要组成部分。T2D 中胰岛素/IGF 轴的破坏以全身和 CRC 细胞代谢重编程、存活和增殖为目标。未来研究阐明分子糖尿病与结直肠癌的联系将有助于预防结直肠癌并降低其在糖尿病人群中的发病率，并且必须指导治疗决策。