Newcastle Magnetic Resonance Centre, Institute for Cellular Medicine, Campus for Ageing and Vitality, Newcastle University, Newcastle upon Tyne, NE4 5PL, UK.
Human Nutrition Research Centre, Institute of Health and Society, Newcastle University, Newcastle upon Tyne, UK.
Diabetologia. 2018 Feb;61(2):273-283. doi: 10.1007/s00125-017-4504-z. Epub 2017 Nov 15.
Using a low-energy diet as a tool, it has been possible to elucidate the sequence of pathophysiological changes that lead to the onset of type 2 diabetes. Negative energy balance in type 2 diabetes causes a profound fall in liver fat content resulting in normalisation of hepatic insulin sensitivity within 7 days. As the period of negative energy balance extends and liver fat levels fall to low normal, the rate of export of triacylglycerol from the liver falls. Consequent to this, the raised pancreas fat content falls and in early type 2 diabetes, normal first-phase insulin secretion becomes re-established with normal plasma glucose control. This research, driven by the predictions of the 2008 twin cycle hypothesis, has led to a paradigm shift in understanding. Studying the reversed sequence of pathophysiological changes, the linked abnormalities in liver and pancreas have been revealed. Early type 2 diabetes is a potentially reversible condition. Surprisingly, it was observed that the diet devised as an experimental tool was actually liked by research participants. It was associated neither with hunger nor tiredness in most people, but with rapidly increased wellbeing. A defined period of weight loss followed by carefully planned weight maintenance-the 'One, Two' approach-has since been applied in clinical practice. Motivated individuals can reverse their type 2 diabetes and remain normoglycaemic over years. A large study is underway to evaluate the applicability of this general approach to routine primary care practice as a long-term management strategy.
通过使用低能量饮食作为工具，已经有可能阐明导致 2 型糖尿病发生的病理生理变化的顺序。2 型糖尿病中的负能平衡导致肝脏脂肪含量显著下降，从而在 7 天内使肝脏胰岛素敏感性正常化。随着负能平衡期的延长和肝脂肪水平降至正常低值，肝脏三酰甘油的输出率下降。因此，升高的胰腺脂肪含量下降，在早期 2 型糖尿病中，正常的第一相胰岛素分泌得以重新建立，同时血糖得到正常控制。这项研究是由 2008 年双循环假说的预测驱动的，它导致了理解的范式转变。通过研究病理生理变化的逆向顺序，揭示了肝脏和胰腺的相关异常。早期 2 型糖尿病是一种潜在可逆转的疾病。令人惊讶的是，人们观察到，作为实验工具设计的饮食实际上受到研究参与者的喜爱。它在大多数人中既不会引起饥饿或疲劳，反而会迅速增加幸福感。随后，在临床实践中应用了经过精心计划的体重维持的“一、二”减肥法。有动力的个体可以逆转 2 型糖尿病，多年来保持正常血糖水平。一项大型研究正在进行中，以评估这种通用方法作为长期管理策略在常规初级保健实践中的适用性。
