Prediabetes, an intermediate stage between normal glucose regulation and type 2 diabetes, is diagnosed based on documentation of impaired fasting glucose, impaired glucose tolerance, or a hemoglobin A1c level of 5.7–6.4%. Individuals with prediabetes have increased risks for the development of type 2 diabetes and multiple vascular complications. Randomized controlled trials have demonstrated the feasibility of preventing progression from prediabetes to type 2 diabetes, using lifestyle or pharmacological interventions. Lifestyle modification has a sustained effect on diabetes prevention, whereas medications lose efficacy when discontinued. Few studies have pre-specified reversal of prediabetes as the primary outcome. There is emerging evidence that reversal of prediabetes (i.e. restoration of normal glucose regulation) confers significant protection from future diabetes and complications, including premature death, during long-term follow-up. Current lifestyle intervention protocols have been more effective in preventing progression from prediabetes to type 2 diabetes than restoring normal glucose regulation; thus, interventions that prevent type 2 diabetes in people with prediabetes do not always reverse prediabetes. Given the compelling benefits of restoration of normal glucose regulation, specific protocols for reversal of prediabetes need to be developed and tested. The design of such protocols requires a deeper understanding of the pathobiology of prediabetes and early glucose dysregulation. The present review focuses on those studies that have assessed the impact of interventions on regression of the prediabetes state and restoration of normal glucose regulation. Furthermore, we discuss alterations in adiposity, glucoregulatory mechanisms, metabolomics, inflammatory markers, and other factors that predict the initial escape from normoglycemia. Such knowledge could inform the future development of novel, refined, and targeted interventions for the reversal prediabetes/early dysglycemia and restoration of normal glucose regulation.

Impact statement

Prediabetes increases the risks of future type 2 diabetes (T2D) and vascular complications, risks that can be prevented by restoring normal glucose regulation (NGR). Few studies have pre-specified reversal of prediabetes and restoration of NGR as primary outcome, and current approaches that prevent T2D in people with prediabetes do not always reverse the prediabetes. The present review focuses on studies that have assessed reversal of the prediabetes, and discusses known and emerging predictors of prediabetes. We argue that fuller knowledge of such predictors could inform the discovery of novel, targeted interventions for reversing prediabetes.

中文翻译：

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从糖尿病前期到正常血糖调节的回归：科学状态。

根据空腹血糖受损，葡萄糖耐量受损或血红蛋白A1c水平为5.7–6.4％的文献，可以诊断出糖尿病前期是正常血糖调节与2型糖尿病之间的中间阶段。患有前驱糖尿病的个体患2型糖尿病和多发性血管并发症的风险增加。随机对照试验证明了使用生活方式或药物干预措施预防从糖尿病前期发展为2型糖尿病的可行性。生活方式的改变对糖尿病的预防具有持续的作用，而停药则失去疗效。很少有研究将预先确定的糖尿病逆转作为主要结局。越来越多的证据表明，糖尿病前期的逆转（即 恢复正常的葡萄糖调节）可在长期随访中为今后的糖尿病和并发症（包括过早死亡）提供重要保护。当前的生活方式干预方案在预防从糖尿病前期发展为2型糖尿病方面比恢复正常的葡萄糖调节更有效。因此，预防患有前驱糖尿病的人的2型糖尿病的干预措施并不总是能逆转前驱糖尿病。鉴于恢复正常葡萄糖调节的引人注目的好处，需要开发和测试用于逆转糖尿病的具体方案。这种方案的设计需要对糖尿病前期和早期葡萄糖异常调节的病理学有更深入的了解。本综述着重于那些评估干预措施对糖尿病前状态的消退和血糖调节正常恢复的影响的研究。此外，我们讨论了肥胖，糖调节机制，代谢组学，炎症标志物以及其他预测正常血糖正常逃逸的因素的改变。这些知识可以为新型的，精确的，有针对性的干预措施的未来发展提供信息，以逆转糖尿病前期/早期血糖异常并恢复正常的血糖调节。

影响陈述

前驱糖尿病会增加未来发生2型糖尿病（T2D）和血管并发症的风险，可以通过恢复正常的葡萄糖调节（NGR）来预防这种风险。很少有研究将预先确定的糖尿病前期逆转和NGR的恢复作为主要预后，而目前预防糖尿病前期人群中T2D的方法并不总是能够逆转糖尿病前期。本综述的重点是评估糖尿病前期逆转的研究，并讨论已知和新兴的糖尿病前期预测因素。我们认为，对此类预测因子的更全面了解可以为发现新颖的，有针对性的干预措施以逆转糖尿病前期提供信息。