Alessandra Macciotta ,1,2 Carlotta Sacerdote,3 Claudia Giachino,1 Chiara Di Girolamo,1 Matteo Franco,1 Yvonne T van der Schouw,4 Raul Zamora-Ros,5 Elisabete Weiderpass,6 Cloé Domenighetti,7 Alexis Elbaz ,7 Thérèse Truong,7 Claudia Agnoli,8 Benedetta Bendinelli,9 Salvatore Panico,10 Paolo Vineis ,11 Sofia Christakoudi,11,12 Matthias B Schulze,13,14,15 Verena Katzke,16 Rashmita Bajracharya,16 Christina C Dahm,17 Susanne Oksbjerg Dalton,18,19 Sandra M Colorado-Yohar,20,21,22 Conchi Moreno-Iribas,23 Pilar Amiano Etxezarreta,21,24,25 María José Sanchez,21,26,27 Nita G Forouhi,28 Nicholas Wareham,28 Fulvio Ricceri 1.
Additional supplemental material is published online only. To view, please visit the journal online (https://doi.org/ 10.1136/jech-2024-222734). For numbered affiliations see end of article.
Correspondence to
Professor Carlotta Sacerdote; 该Email地址已收到反垃圾邮件插件保护。要显示它您需要在浏览器中启用JavaScript。 NW and FR contributed equally. Received 10 July 2024 Accepted 19 November 2024© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group
To cite: Macciotta A, Sacerdote C, Giachino C, et al. J Epidemiol Community Health Epub ahead of print:[please include Day MonthYear]. doi:10.1136/jech- 2024-222734
ABSTRACT
Introduction Observational studies have shown that more educated people are at lower risk of developing type 2 diabetes (T2D). However, robust study designs are needed to investigate the likelihood that such a relationship is causal. This study used genetic instruments for education to estimate the effect of education on T2D using the Mendelian randomisation (MR) approach.
Methods Analyses have been conducted in the European Prospective Investigation into Cancer and Nutrition (EPIC)- InterAct study (more than 20000 individuals), a case-cohort study of T2D nested in the EPIC cohort. Education was measured as Years of Education and Relative Index of Inequality. Prentice-weighted Cox models were performed to estimate the association between education and T2D. One-sample MR analyses investigated whether genetic predisposition towards longer education was associated with risk of T2D and investigated potential mediators of the
Results MR estimates indicated a risk reduction of about 15% for each year of longer education on the risk of developing T2D, confirming the protective role estimated by observational models (HR 0.96, 95% CI 0.95 to 0.96). MR analyses on putative mediators showed a significant role of education on body mass index, alcohol consumption, adherence to the Mediterranean diet and smoking habits.
Conclusion The results supported the hypothesis that higher education is a protective factor for the risk of developing T2D. Based on its position in the causal chain, education may be antecedent of other known risk factors for T2D including unhealthy behaviours. These findings reinforce evidence obtained through observational study designs and bridge the gap between correlation and causation.
Stephanie J. Hanna1 · Rachel H. Bonami2,3,4,5 · Brian Corrie6,7 · Monica Westley8 · Amanda L. Posgai9 · Eline T. Luning Prak10 · Felix Breden6,7 · Aaron W. Michels11 · Todd M. Brusko9,12,13 · Type 1 Diabetes AIRR Consortium
Received: 26 May 2024 / Accepted: 19 August 2024 / Published online: 29 October 2024
© The Author(s) 2024
Extended author information available on the last page of the article
Abstract
Human molecular genetics has brought incredible insights into the variants that confer risk for the development of tissuespecific autoimmune diseases, including type 1 diabetes. The hallmark cell-mediated immune destruction that is characteristic of type 1 diabetes is closely linked with risk conferred by the HLA class II gene locus, in combination with a broad array of additional candidate genes influencing islet-resident beta cells within the pancreas, as well as function, phenotype and trafficking of immune cells to tissues. In addition to the well-studied germline SNP variants, there are critical contributions conferred by T cell receptor (TCR) and B cell receptor (BCR) genes that undergo somatic recombination to yield the Adaptive Immune Receptor Repertoire (AIRR) responsible for autoimmunity in type 1 diabetes. We therefore created the T1D TCR/ BCR Repository (The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository) to study these highly variable and dynamic gene rearrangements. In addition to processed TCR and BCR sequences, the T1D TCR/BCR Repository includes detailed metadata (e.g. participant demographics, disease-associated parameters and tissue type). We introduce the Type 1 Diabetes AIRR Consortium goals and outline methods to use and deposit data to this comprehensive repository. Our ultimate goal is to facilitate research community access to rich, carefully annotated immune AIRR datasets to enable new scientific inquiry and insight into the natural history and pathogenesis of type 1 diabetes.
Keywords AIRR · AIRR Data Commons · Autoantibodies · B cell receptors · FAIR data · Next-generation sequencing · Single-cell RNA-seq · T cell receptors · Type 1 diabetes
Abbreviations
AAb Autoantibody/autoantibodies
ADC AIRR Data Commons
AIM Activation-induced marker
AIRR Adaptive Immune Receptor Repertoire
AIRR-seq AIRR sequencing
BCR B cell receptor
CDR3 Complementarity determining region 3
FAIR Findable, Accessible, Interoperable, Reusable
GEO Gene Expression Omnibus
HPAP Human Pancreas Analysis Program
IEDB Immune Epitope Database
MiAIRR Minimal information about AIRR
ML Machine learning
pLN Pancreatic lymph node(s)
SARS-CoV-2 Severe acute respiratory syndrome coronavirus 2
scRNA-seq Single-cell RNA-seq
SRA Sequence Read Archive
T1D TCR/BCR Repository The Type 1 Diabetes T Cell Receptor and B Cell Receptor Repository
TCR T cell receptor
TCRβ T cell receptor β chain
Tfh T follicular helper
Treg Regulatory T cell(s)
VDJ Variable, diversity and joining gene segments
Stephanie J. Hanna and Rachel H. Bonami contributed equally to this work. Aaron W. Michels and Todd M. Brusko contributed equally as joint senior authors.
Members of the Type 1 Diabetes AIRR Consortium are listed in the Acknowledgements.
原创: 十六点五 中山二院糖尿病足中心
糖尿病足部的慢性溃疡是否存在感染,好像应该是没有多少疑问的,但在所谓的“神经性溃疡”的表面是否存在有临床意义的感染,一直有争议。
对于外周血管病变的介入治疗,较IWGDF指南较有关OFFLOADING的细节描述,有关介入治疗的部分实在是比较粗慥,目前糖尿病外周血管病变介入治疗的热点问题大部分都没有涉及
对于糖尿病外周血管病变的治疗,2019年版IWGDF指南讲的比较少,无论是内科治疗还是介入治疗,这版的指南都讲得比较少(其实之前版本的IWGDF指南有关血管病变方面的内容更少),而国内糖尿病足指南,提到有关糖尿病外周血管病变治疗,一般都会用比较大的篇幅谈到其内科治疗。
人们对于糖尿病外周血管病变越来越关注,一方面,它是糖尿病足形成的最重要的原因;另一方面,它也是糖尿病进展到一定程度的标志,严重的糖尿病外周血管病变,往往标志着糖尿病进展到晚期,心、肾、脑、眼底等重要脏器的血管也存在严重的问题,而糖尿病足长期的皮肤溃疡不愈合,其产生的大量炎症因子,也会加重这些血管病变,因此,如何评价(诊断)及治疗糖尿病外周血管病变,成为了糖尿病诊断和治疗的最重要的领域。
伤口世界平台生态圈,以“关爱人间所有伤口患者”为愿景,连接、整合和拓展线上和线下的管理慢性伤口的资源,倡导远程、就近和居家管理慢性伤口,解决伤口专家的碎片化时间的价值创造、诊疗经验的裂变复制、和患者的就近、居家和低成本管理慢性伤口的问题。
2019广东省医疗行业协会伤口管理分会年会
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