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Diabetology and Metabolic Syndrome

, 9:47

First Online: 19 June 2017Received: 10 February 2017Accepted: 08 June 2017DOI: 10.1186-s13098-017-0245-x

Cite this article as: van Herpt, T.T.W., Lemmers, R.F.H., van Hoek, M. et al. Diabetol Metab Syndr 2017 9: 47. doi:10.1186-s13098-017-0245-x

Abstract

BackgroundType 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.

MethodsThe 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.

ResultsIn 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.

ConclusionsIn 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.

KeywordsType 2 diabetes mellitus Cardiovascular disease Prospective follow-up Complications Genetics Case–control AbbreviationsACRalbumin-creatinine-ratio

BMIbody mass index

CABGcoronary arterial bypass graft

DNAdeoxyribonucleic acid

EDTAethylene diamine tetra acetic

HbA1cglycated hemoglobin

HDLhigh-density lipoprotein

IQRinterquartile range

LDLlow-density lipoprotein

MALDI-FTICRmatrix-assisted laser desorption–ionization-Fourier transform ion cyclotron resonance mass spectrometry

MALDI-TOFmatrix-assisted laser desorption–ionization-time of flight

PCIpercutaneous coronary intervention

T2DMtype 2 diabetes mellitus

Electronic supplementary materialThe online version of this article doi:10.1186-s13098-017-0245-x contains supplementary material, which is available to authorized users.

Thijs T. W. van Herpt, Roosmarijn F. H. Lemmers and Mandy van Hoek have contributed equally to this work





Autor: Thijs T. W. van Herpt - Roosmarijn F. H. Lemmers - Mandy van Hoek - Janneke G. Langendonk - Ronald J. Erdtsieck - Ber

Fuente: https://link.springer.com/







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