Muñoz-Hernández Liliana, Márquez-López Ziomara, Mehta Roopa, Aguilar-Salinas Carlos Alberto
Metabolic Diseases Research Unit, Instituto Nacional de Ciencias Medicas y Nutricion, Mexico City, Mexico.
Consejo Nacional de Ciencia y Tecnología, Mexico City, Mexico.
Curr Diab Rep. 2020 Mar 12;20(4):13. doi: 10.1007/s11892-020-1295-2.
Diet is a pillar of type 2 diabetes mellitus (T2DM) management. Intermittent fasting (IF) is postulated as a novel approach, able to improve glucose control and potentially capable of reversing some of the pathophysiological alterations of this condition. In this review, the molecular and clinical evidence of diets based on intermittent energy restriction (IER) in laboratory animal models and subjects with type 2 diabetes is discussed. The mechanisms through which IF are thought to improve glucose homeostasis and reverse β cell failure are also reviewed.
Studies derived from murine models suggest that IER is associated with improvements in β cell function and insulin resistance. Two main mechanisms have been demonstrated, one derived from the autophagy-lysosome pathway and, the other from an increase in neurogenin3 (Ngn3) levels (a marker for endocrine progenitor cells like β cells during development). Notably, IER also promotes reconstruction of gut microbiota. In mice, all effects were independent of weight loss. By contrast, in human studies, outcomes are widely attributable to weight loss. The more consistent results are reductions in body weight, visceral fat, and glucose and insulin levels. Increases in HDL cholesterol levels are also frequently reported. The decrease in insulin levels observed in humans is in opposition with the increase reported in mice, suggesting that the main mechanism in humans is an improvement in peripheral insulin action. Recommending diets based on intermittent fasting in humans is based on the promising results found in animal models where an improvement in β cell function has been recorded. β cell function after IF has not been assessed in human subjects with T2DM. This review provides information regarding different protocols for the implementation of IF in diabetic persons and also provides important safety advice in order to avoid adverse effects. Clinical studies do not show an increased risk of hypoglycemia, and a recent case series reported reversal of T2DM.
饮食是2型糖尿病（T2DM）管理的支柱。间歇性禁食（IF）被认为是一种新方法，能够改善血糖控制，并有可能逆转该疾病的一些病理生理改变。在本综述中，我们讨论了基于间歇性能量限制（IER）的饮食在实验动物模型和2型糖尿病患者中的分子和临床证据。我们还综述了IF被认为可改善葡萄糖稳态和逆转β细胞功能衰竭的机制。
来自小鼠模型的研究表明，IER与β细胞功能和胰岛素抵抗的改善有关。已证实有两种主要机制，一种源自自噬-溶酶体途径，另一种源自神经生成素3（Ngn3）水平的升高（Ngn3是发育过程中β细胞等内分泌祖细胞的标志物）。值得注意的是，IER还促进肠道微生物群的重建。在小鼠中，所有这些效应均与体重减轻无关。相比之下，在人体研究中，结果大多归因于体重减轻。更一致的结果是体重、内脏脂肪、血糖和胰岛素水平降低。高密度脂蛋白胆固醇水平升高也经常被报道。在人类中观察到的胰岛素水平下降与在小鼠中报道的升高相反，这表明人类的主要机制是外周胰岛素作用的改善。基于动物模型中记录到的β细胞功能改善这一有前景的结果，人们建议在人类中采用基于间歇性禁食的饮食。IF后β细胞功能尚未在T2DM患者中进行评估。本综述提供了关于糖尿病患者实施IF的不同方案的信息，并提供了重要的安全建议以避免不良反应。临床研究未显示低血糖风险增加，并且最近的一个病例系列报道了T2DM的逆转。
