Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, Skåne University Hospital Malmö, Malmö, Sweden.
Danish Diabetes Academy, Odense, Denmark.
Clin Chem. 2018 Jan;64(1):130-141. doi: 10.1373/clinchem.2017.273540. Epub 2017 Nov 2.
Type 2 diabetes is highly prevalent and devastating. Obesity is a diabetogenic factor, driving insulin resistance and a compensatory demand for increased insulin secretion from the pancreatic β cells; a failure to address this demand results in diabetes. Accordingly, primary and secondary prevention of obesity are at the core of diabetes prevention programs. The development of obesity and declining β-cell function often span many years or decades before diabetes is clinically manifest. Thus, characterizing the early-life process and risk factors that set disease trajectories may yield novel targets for early intervention and help improve the accuracy of prediction algorithms, factors germane to the emerging field of precision medicine.
Here, we overview the concepts of precision medicine and fetal programming. We discuss the barriers to preventing obesity and type 2 diabetes in adulthood and present the rationale for considering early-life events in this context. In so doing, we discuss proof-of-concept studies and cutting-edge technological developments that are likely to transform current thinking on the etiology and pathogenesis of obesity and type 2 diabetes. We also review the factors hampering progress, including the success and failures of pregnancy intervention trials.
Obesity and type 2 diabetes are among the major health and economic burdens of our time. Defeating these diseases is likely to require life-course approaches, which may include aggressive interventions informed by biomarker profiling undertaken during early life.
2 型糖尿病的发病率极高，且后果严重。肥胖是致病因素之一，会导致胰岛素抵抗以及胰岛β细胞分泌更多胰岛素的代偿性需求增加；如果不能满足这种需求，就会导致糖尿病。因此，肥胖的一级和二级预防是糖尿病预防计划的核心。肥胖的发展和β细胞功能的下降通常在糖尿病出现临床症状前的数年或数十年内发生。因此，描述导致疾病轨迹的早期生命过程和危险因素可能为早期干预提供新的目标，并有助于提高预测算法的准确性，这对于新兴的精准医学领域至关重要。
本文概述了精准医学和胎儿编程的概念。我们讨论了在成年期预防肥胖和 2 型糖尿病的障碍，并提出了在这种情况下考虑早期生命事件的理由。在这一过程中，我们讨论了概念验证研究和前沿技术的发展，这些研究和发展可能会改变对肥胖和 2 型糖尿病病因和发病机制的现有认识。我们还回顾了阻碍进展的因素，包括妊娠干预试验的成功和失败。
肥胖和 2 型糖尿病是当今主要的健康和经济负担之一。要战胜这些疾病，可能需要采取终生方法，其中可能包括根据生命早期进行的生物标志物分析进行积极干预。
