Gender and biological sex impact the pathogenesis of numerous diseases, including metabolic disorders such as diabetes. In most parts of the world, diabetes is more prevalent in men than in women, especially in middle-aged populations. In line with this, considering almost all animal models, males are more likely to develop obesity, insulin resistance and hyperglycaemia than females in response to nutritional challenges. As summarised in this review, it is now obvious that many aspects of energy balance and glucose metabolism are regulated differently in males and females and influence their predisposition to type 2 diabetes. During their reproductive life, women exhibit specificities in energy partitioning as compared with men, with carbohydrate and lipid utilisation as fuel sources that favour energy storage in subcutaneous adipose tissues and preserve them from visceral and ectopic fat accumulation. Insulin sensitivity is higher in women, who are also characterised by higher capacities for insulin secretion and incretin responses than men; although, these sex advantages all disappear when glucose tolerance deteriorates towards diabetes. Clinical and experimental observations evidence the protective actions of endogenous oestrogens, mainly through oestrogen receptor α activation in various tissues, including the brain, the liver, skeletal muscle, adipose tissue and pancreatic beta cells. However, beside sex steroids, underlying mechanisms need to be further investigated, especially the role of sex chromosomes, fetal/neonatal programming and epigenetic modifications. On the path to precision medicine, further deciphering sex-specific traits in energy balance and glucose homeostasis is indeed a priority topic to optimise individual approaches in type 2 diabetes prevention and treatment.

中文翻译：

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代谢调节和糖尿病易感性方面的性别差异。

性别和生物性别会影响多种疾病的发病机理，包括糖尿病等代谢性疾病。在世界上大多数地区，尤其是在中年人群中，男性比女性患糖尿病更为普遍。因此，考虑到几乎所有动物模型，应对营养挑战，雄性比雌性更容易出现肥胖，胰岛素抵抗和高血糖。如本综述所述，现在很明显，男性和女性对能量平衡和葡萄糖代谢的许多方面都有不同的调节，并影响了他们患2型糖尿病的易感性。与男性相比，女性在生育过程中表现出能量分配的特异性，碳水化合物和脂质的利用为燃料，有利于能量在皮下脂肪组织中的储存，并防止内脏和异位脂肪的积累。女性对胰岛素的敏感性更高，女性的胰岛素分泌和肠降血糖素反应能力也高于男性。但是，当葡萄糖耐量恶化对糖尿病时，这些性别优势都会消失。临床和实验观察证明内源性雌激素的保护作用，主要是通过在各种组织（包括脑，肝，骨骼肌，脂肪组织和胰腺β细胞）中的雌激素受体α活化来实现的。但是，除了性类固醇外，还需要进一步研究其潜在机制，特别是性染色体，胎儿/新生儿程序和表观遗传修饰的作用。