Diabetes following SARS-CoV-2 infection: Incidence, persistence, and implications of COVID-19 vaccination. A cohort study of fifteen million people
Diabetes following SARS-CoV-2 infection: Incidence, persistence, and implications of COVID-19 vaccination. A cohort study of fifteen million people
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SARS-CoV-2 感染后糖尿病：发病率、持续性以及 COVID-19 疫苗接种的影响。
DOI：
10.1101/2023.08.07.23293778
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Taylor K
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作者：
Taylor K
背景2型糖尿病（T2 DM）的发病率在COVID-19确诊后增加。疫苗接种对这一增长的影响，持续多久，以及COVID-19对其他类型糖尿病的影响尚不清楚。（N= 15，211，471，2020年1月至2021年12月），接种疫苗（N = 11，822，640）和未接种疫苗（N= 2，851，183）队列（2021年6月至12月），使用链接的电子健康记录。我们估计了调整后的风险比（aHR），将COVID-19诊断后的糖尿病发病率与诊断前或诊断后102周内的发病率进行比较。结果按COVID-19严重程度（住院/未住院）和糖尿病类型分层。结果在接种前队列中，COVID-19后T2 DM发病率的aHRS（与诊断前或未诊断相比）从第1-4周的3.01（95%CI：2.76，3.28）下降至第53-102周的1.24（1.12，1.38）。未接种疫苗者的aHRS高于接种疫苗者（4.86（3.69，6.41））对比1.42（1.24，1.62）在第1-4周）和住院COVID-19（接种前队列21.1（18.8，23.7）在第1-4周下降至2.04（1.65，2.51）在第52-102周），比非住院COVID-19（1.45（1.27，1.64）在第1-4周，1.10（0.98，1.23）在第52-102周）。对于73%的确诊患者，T2 DM在COVID-19后持续4个月。1型糖尿病的模式相似，尽管COVID-19后超过一年的发病率没有持续过高。解释COVID-19后住院患者的T2 DM发病率升高比非住院患者更高，持续时间更长。接种疫苗后明显不太明显。严重COVID-19后的T2 DM检测和疫苗接种推广是解决这一公共卫生问题的重要工具。研究背景研究本研究之前的证据我们检索了PubMed，以2019年12月1日至2023年7月12日期间发表的基于人群的观察性研究，这些研究考察了SARS-CoV-2感染或COVID-19诊断之间的关联（搜索字符串：SARS-CoV-2或COVID* 或冠状病毒 *）和随后发生的糖尿病（搜索词：糖尿病）。十九项相关研究; 8例有糖尿病类型的复合结局，6例按糖尿病类型分层，5例仅与1型糖尿病（T1 DM）相关。我们没有发现任何与妊娠期或其他类型糖尿病相关的研究。11项研究来自美国，3项来自英国，2项来自德国，1项来自加拿大，1项来自丹麦，1项来自韩国。大多数研究描述了SARS-CoV-2感染后1至2年的累积相对风险（感染与未感染）为1.2至2.6，尽管4项研究发现急性期后与T1 DM无关。所有的研究都缺乏在人群亚组中比较糖尿病类型、严重程度和疫苗接种状况的相对风险的能力。一项研究通过疫苗接种状况检查了相对风险，但该研究使用了糖尿病和糖尿病的复合结局，并且在主要为白色男性人群中进行。两项T1 DM研究发现，在COVID-19诊断后30天内没有证据表明风险升高，而两项研究报告了6个月后的风险升高。两项2型糖尿病（T2 DM）研究通过感染后时间段检查了相对风险：一项美国保险索赔研究报告了感染后6个月的持续关联，而一项大型英国人群研究报告了12周后的关联。然而，后一项研究仅使用了初级保健数据，因此COVID-19病例可能未得到充分确认。
BackgroundType 2 diabetes (T2DM) incidence is increased after diagnosis of COVID-19. The impact of vaccination on this increase, for how long it persists, and the effect of COVID-19 on other types of diabetes remain unclear.MethodsWith NHS England approval, we studied diabetes incidence following COVID-19 diagnosis in pre-vaccination (N=15,211,471, January 2020-December 2021), vaccinated (N =11,822,640), and unvaccinated (N=2,851,183) cohorts (June-December 2021), using linked electronic health records. We estimated adjusted hazard ratios (aHRs) comparing diabetes incidence post-COVID-19 diagnosis with incidence before or without diagnosis up to 102 weeks post-diagnosis. Results were stratified by COVID-19 severity (hospitalised/non-hospitalised) and diabetes type.FindingsIn the pre-vaccination cohort, aHRS for T2DM incidence after COVID-19 (compared to before or without diagnosis) declined from 3.01 (95% CI: 2.76,3.28) in weeks 1-4 to 1.24 (1.12,1.38) in weeks 53-102. aHRS were higher in unvaccinated than vaccinated people (4.86 (3.69,6.41)) versus 1.42 (1.24,1.62) in weeks 1-4) and for hospitalised COVID-19 (pre-vaccination cohort 21.1 (18.8,23.7) in weeks 1-4 declining to 2.04 (1.65,2.51) in weeks 52-102), than non-hospitalised COVID-19 (1.45 (1.27,1.64) in weeks 1-4, 1.10 (0.98,1.23) in weeks 52-102). T2DM persisted for 4 months after COVID-19 for ∼73% of those diagnosed. Patterns were similar for Type 1 diabetes, though excess incidence did not persist beyond a year post-COVID-19.InterpretationElevated T2DM incidence after COVID-19 is greater, and persists longer, in hospitalised than non-hospitalised people. It is markedly less apparent post-vaccination. Testing for T2DM after severe COVID-19 and promotion of vaccination are important tools in addressing this public health problem.Research in contextEvidence before this studyWe searched PubMed for population-based observational studies published between December 1st 2019 and July 12th 2023 examining associations between SARS-CoV-2 infection or COVID-19 diagnosis (search string: SARS-CoV-2 or COVID* or coronavirus*) and subsequent incident diabetes (search term: diabetes). Of nineteen relevant studies; eight had a composite outcome of diabetes types, six stratified by diabetes type and five pertained to type-1-diabetes (T1DM) only. We did not identify any studies relating to gestational or other types of diabetes. Eleven studies were from the US, three from the UK, two from Germany, one from Canada, one from Denmark and one from South Korea.Most studies described cumulative relative risks (for infection versus no infection) one to two years post-SARS-CoV-2 infection of 1.2 to 2.6, though four studies found no associations with T1DM after the post-acute period. All studies lacked the power to compare diabetes relative risk by type, severity, and vaccination status in population subgroups. One study examined relative risks by vaccination status, but this used a composite outcome of diabetes and hyperlipidaemia and was conducted in a predominantly white male population.Two studies of T1DM found no evidence of elevated risk beyond 30 days after COVID-19 diagnosis, whilst two reported elevated risks at six months. Two studies of type 2 diabetes (T2DM) examined relative risks by time period post-infection: one study of US insurance claims reported a persistent association six months post-infection, whereas a large UK population-based study reported no associations after 12 weeks. However, the latter study used only primary care data, therefore COVID-19 cases were likely to have been under-ascertained.No large studies …