van Herpt Thijs T W, Lemmers Roosmarijn F H, van Hoek Mandy, Langendonk Janneke G, Erdtsieck Ronald J, Bravenboer Bert, Lucas Annelies, Mulder Monique T, Haak Harm R, Lieverse Aloysius G, Sijbrands Eric J G
Department of Internal Medicine, Erasmus Medical Center, P. O. Box 2040, 3000 CA Rotterdam, The Netherlands.
Department of Internal Medicine, Máxima Medical Center, Ds Th Fliednerstraat 1, 5631 BM Eindhoven, The Netherlands.
Diabetol Metab Syndr. 2017 Jun 19;9:47. doi: 10.1186/s13098-017-0245-x. eCollection 2017.
Type 2 diabetes is a major healthcare problem. Glucose-, lipid-, and blood pressure-lowering strategies decrease the risk of micro- and macrovascular complications. However, a substantial residual risk remains. To unravel the etiology of type 2 diabetes and its complications, large-scale, well-phenotyped studies with prospective follow-up are needed. This is the goal of the DiaGene study. In this manuscript, we describe the design and baseline characteristics of the study.
The DiaGene study is a multi-centre, prospective, extensively phenotyped type 2 diabetes cohort study with concurrent inclusion of diabetes-free individuals at baseline as controls in the city of Eindhoven, The Netherlands. We collected anthropometry, laboratory measurements, DNA material, and detailed information on medication usage, family history, lifestyle and past medical history. Furthermore, we assessed the prevalence and incidence of retinopathy, nephropathy, neuropathy, and diabetic feet in cases. Using logistic regression models, we analyzed the association of 11 well known genetic risk variants with type 2 diabetes in our study.
In total, 1886 patients with type 2 diabetes and 854 controls were included. Cases had worse anthropometric and metabolic profiles than controls. Patients in outpatient clinics had higher prevalence of macrovascular (41.9% vs. 34.8%; P = 0.002) and microvascular disease (63.8% vs. 20.7%) compared to patients from primary care. With the exception of the genetic variant in KCNJ11, all type 2 diabetes susceptibility variants had higher allele frequencies in subjects with type 2 diabetes than in controls.
In our study population, considerable rates of macrovascular and microvascular complications are present despite treatment. These prevalence rates are comparable to other type 2 diabetes populations. While planning genomics, we describe that 11 well-known type 2 diabetes genetic risk variants (in TCF7L2, PPARG-P12A, KCNJ11, FTO, IGF2BP2, DUSP9, CENTD2, THADA, HHEX, CDKAL1, KCNQ1) showed similar associations compared to literature. This study is well-suited for multiple omics analyses to further elucidate disease pathophysiology. Our overall goal is to increase the understanding of the underlying mechanisms of type 2 diabetes and its complications for developing new prediction, prevention, and treatment strategies.
2型糖尿病是一个重大的医疗保健问题。降低血糖、血脂和血压的策略可降低微血管和大血管并发症的风险。然而，仍存在相当大的残余风险。为了阐明2型糖尿病及其并发症的病因，需要进行大规模、具有良好表型且有前瞻性随访的研究。这就是DiaGene研究的目标。在本手稿中，我们描述了该研究的设计和基线特征。
DiaGene研究是一项多中心、前瞻性、具有广泛表型的2型糖尿病队列研究，在荷兰埃因霍温市基线时同时纳入无糖尿病个体作为对照。我们收集了人体测量数据、实验室检测结果、DNA样本以及关于药物使用、家族史、生活方式和既往病史的详细信息。此外，我们评估了病例中视网膜病变、肾病、神经病变和糖尿病足的患病率和发病率。使用逻辑回归模型，我们分析了11个已知的遗传风险变异与本研究中2型糖尿病的关联。
总共纳入了1886例2型糖尿病患者和854例对照。病例的人体测量和代谢特征比对照更差。与初级保健患者相比，门诊患者的大血管疾病患病率更高（41.9%对34.8%；P = 0.002），微血管疾病患病率也更高（63.8%对20.7%）。除了KCNJ11基因变异外，所有2型糖尿病易感性变异在2型糖尿病患者中的等位基因频率均高于对照。
在我们的研究人群中，尽管进行了治疗，但大血管和微血管并发症的发生率仍然很高。这些患病率与其他2型糖尿病人群相当。在规划基因组学研究时，我们发现与文献报道相比，11个已知的2型糖尿病遗传风险变异（位于TCF7L2、PPARG - P12A、KCNJ11、FTO、IGF2BP2、DUSP9、CENTD2、THADA、HHEX、CDKAL1、KCNQ1）显示出相似的关联。这项研究非常适合进行多种组学分析，以进一步阐明疾病的病理生理学。我们的总体目标是增进对2型糖尿病及其并发症潜在机制的理解，从而制定新的预测、预防和治疗策略。
