Division of Endocrinology and the Hallett Center for Diabetes and Endocrinology, Alpert Medical School of Brown University, Providence, Rhode Island 02903, USA.
J Clin Endocrinol Metab. 2010 Apr;95(4):1566-74. doi: 10.1210/jc.2009-1966. Epub 2010 Mar 1.
Type 2 diabetes is heterogeneous in its clinical features, pathogenesis, and predisposing or causal genetic factors. This report examines what is known and what needs to be learned about the potential to individualize glycemic therapies in type 2 diabetes, based on phenotypes and genotypes.
A 29-member international working group with expertise in diabetes epidemiology, physiology, genetics, clinical trials, and clinical care participated in formal presentations and discussions at a conference on April 16-17, 2009. A writing group subsequently prepared this summary and recommendations. The conference was coendorsed by The Endocrine Society and the American Diabetes Association and was supported by an unrestricted educational grant from Novo Nordisk.
Participants reviewed and discussed published literature, plus their own unpublished data.
The summary and recommendations were supported unanimously by the writing group as representing the majority or unanimous opinions of the working group.
Recent advances in genetics, such as the identification of Kir6.2 mutations and the responsible genes for several forms of maturity onset diabetes of the young (MODY), have established precedents linking specifically effective therapies to defined diabetes subtypes. The recent increase in identified polygenic factors related to type 2 diabetes and our understanding of the pathogenesis of diabetes provide potential opportunities to individualize therapy. To further this process, we recommend expanded analysis of existing data sources and the development of new basic and clinical research studies, including a greater focus on identifying type 2 diabetes subtypes, their response to different therapies, and quantitation of cost-effectiveness.
2 型糖尿病在其临床特征、发病机制和易感性或因果遗传因素方面存在异质性。本报告根据表型和基因型,考察了在 2 型糖尿病中对血糖治疗进行个体化的潜力,以及目前已经了解和需要进一步了解的内容。
一个由 29 名国际专家组成的工作组,他们在糖尿病流行病学、生理学、遗传学、临床试验和临床护理方面拥有专业知识,参加了 2009 年 4 月 16 日至 17 日举行的一次会议上的正式报告和讨论。一个写作小组随后编写了这份总结和建议。该会议由内分泌学会和美国糖尿病协会共同认可,并得到诺和诺德公司的一项无限制教育赠款的支持。
与会者审查并讨论了已发表的文献以及他们自己未发表的数据。
写作小组一致支持该总结和建议,认为它们代表了工作组的多数或一致意见。
遗传学方面的最新进展,例如 Kir6.2 突变的鉴定以及几种青年发病型成年糖尿病(MODY)的相关基因的鉴定,为将特定有效的治疗方法与特定的糖尿病亚型联系起来建立了先例。最近与 2 型糖尿病相关的多基因因素的增加以及我们对糖尿病发病机制的理解为个体化治疗提供了潜在的机会。为了进一步推进这一进程,我们建议扩大对现有数据源的分析,并开展新的基础和临床研究,包括更多地关注鉴定 2 型糖尿病亚型、它们对不同治疗方法的反应以及量化成本效益。