Koivula Robert W, Heggie Alison, Barnett Anna, Cederberg Henna, Hansen Tue H, Koopman Anitra D, Ridderstråle Martin, Rutters Femke, Vestergaard Henrik, Gupta Ramneek, Herrgård Sanna, Heymans Martijn W, Perry Mandy H, Rauh Simone, Siloaho Maritta, Teare Harriet J A, Thorand Barbara, Bell Jimmy, Brunak Søren, Frost Gary, Jablonka Bernd, Mari Andrea, McDonald Tim J, Dekker Jacqueline M, Hansen Torben, Hattersley Andrew, Laakso Markku, Pedersen Oluf, Koivisto Veikko, Ruetten Hartmut, Walker Mark, Pearson Ewan, Franks Paul W
Department of Clinical Sciences, Lund University, Genetic and Molecular Epidemiology, CRC, Skåne University Hospital Malmö, Building 91, Level 10, Jan Waldenströms gata 35, SE-205 02, Malmö, Sweden.
Diabetologia. 2014 Jun;57(6):1132-42. doi: 10.1007/s00125-014-3216-x. Epub 2014 Apr 4.
AIMS/HYPOTHESIS: The DIRECT (Diabetes Research on Patient Stratification) Study is part of a European Union Framework 7 Innovative Medicines Initiative project, a joint undertaking between four industry and 21 academic partners throughout Europe. The Consortium aims to discover and validate biomarkers that: (1) predict the rate of glycaemic deterioration before and after type 2 diabetes onset; (2) predict the response to diabetes therapies; and (3) help stratify type 2 diabetes into clearly definable disease subclasses that can be treated more effectively than without stratification. This paper describes two new prospective cohort studies conducted as part of DIRECT.
Prediabetic participants (target sample size 2,200-2,700) and patients with newly diagnosed type 2 diabetes (target sample size ~1,000) are undergoing detailed metabolic phenotyping at baseline and 18 months and 36 months later. Abdominal, pancreatic and liver fat is assessed using MRI. Insulin secretion and action are assessed using frequently sampled OGTTs in non-diabetic participants, and frequently sampled mixed-meal tolerance tests in patients with type 2 diabetes. Biosamples include venous blood, faeces, urine and nail clippings, which, among other biochemical analyses, will be characterised at genetic, transcriptomic, metabolomic, proteomic and metagenomic levels. Lifestyle is assessed using high-resolution triaxial accelerometry, 24 h diet record, and food habit questionnaires.
CONCLUSIONS/INTERPRETATION: DIRECT will yield an unprecedented array of biomaterials and data. This resource, available through managed access to scientists within and outside the Consortium, will facilitate the development of new treatments and therapeutic strategies for the prevention and management of type 2 diabetes.
目的/假设：DIRECT（糖尿病患者分层研究）是欧盟第七框架创新药物计划项目的一部分，由欧洲四个行业和21个学术合作伙伴共同开展。该联盟旨在发现和验证生物标志物，这些标志物能够：（1）预测2型糖尿病发病前后血糖恶化的速率；（2）预测糖尿病治疗的反应；（3）帮助将2型糖尿病分层为明确可定义的疾病亚类，相较于未分层的情况，这些亚类能够得到更有效的治疗。本文描述了作为DIRECT一部分进行的两项新的前瞻性队列研究。
糖尿病前期参与者（目标样本量2200 - 2700）和新诊断的2型糖尿病患者（目标样本量约1000）在基线、18个月和36个月后接受详细的代谢表型分析。使用MRI评估腹部、胰腺和肝脏脂肪。在非糖尿病参与者中，通过频繁采样的口服葡萄糖耐量试验评估胰岛素分泌和作用，在2型糖尿病患者中，通过频繁采样的混合餐耐量试验进行评估。生物样本包括静脉血、粪便、尿液和指甲剪，除其他生化分析外，还将在基因、转录组、代谢组、蛋白质组和宏基因组水平进行特征分析。使用高分辨率三轴加速度计、24小时饮食记录和饮食习惯问卷评估生活方式。
结论/解读：DIRECT将产生前所未有的一系列生物材料和数据。通过联盟内外科学家的管理访问可获取该资源，这将促进2型糖尿病预防和管理新治疗方法及治疗策略的开发。
