Impact of autoimmune diseases on risk of pancreatic endocrine and exocrine diseases: a prospective cohort study based on the UK Biobank
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摘要:目的
分析自身免疫性疾病(AIDs)与胰腺内分泌和外分泌疾病发生风险的相关性。
方法纳入来自英国生物样本库中的451 497名参与者, 主要结局为胰腺内分泌和外分泌疾病。使用国际疾病分类9/10(ICD9/10)代码定义各个AIDs以及胰腺内分泌和外分泌疾病。采用多变量Cox风险模型对年龄、性别、种族、汤森剥夺指数、吸烟、饮酒、体质量指数、腰围、臀围、合并高血压、血脂异常和胆结石进行校正，评估AIDs与胰腺内分泌和外分泌疾病的关系。
结果共纳入415 497名参与者，其中37 482例在随访期间出现胰腺相关疾病。AIDs患者中，胰腺外分泌疾病、内分泌疾病的患者比率增高，差异有统计学意义(P < 0.05)。类风湿关节炎[HR (95% CI)=1.438(1.161~1.781)]、强直性脊柱炎[HR (95% CI)=1.675(1.009~2.780)]、溃疡性结肠炎[HR (95% CI)=1.335(1.037~1.719)]和克罗恩病[HR (95% CI)=1.530(1.154~2.028)]均与胰腺外分泌疾病发生风险增加相关(P均 < 0.05);类风湿关节炎[HR (95% CI)=1.119(1.004~1.248)]、溃疡性结肠炎[HR (95% CI)=1.324(1.175~1.491)]、系统性硬化症[HR (95% CI)=2.08(1.355~3.191)]和克罗恩病[HR (95% CI)=1.394(1.197~1.624)]均与胰腺内分泌疾病发生风险增加有关(P均 < 0.05)。
结论总体的AIDs以及部分特定的AIDs与胰腺内分泌和外分泌疾病风险增加相关，临床上应重视AIDs患者并发胰腺疾病的早期预防。
Abstract:ObjectiveTo analyze the correlations of autoimmune diseases (AIDs) with the risk of developing pancreatic endocrine and exocrine diseases.
MethodsA total of 451, 497 participants from the UK Biobank were recruited, with the primary outcomes being pancreatic endocrine and exocrine diseases. International Classification of Diseases 9/10 (ICD9/10) codes were used to define each AIDs, the pancreatic endocrine and exocrine diseases. Multivariable Cox proportional hazards models were employed to assess the relationships between AIDs and pancreatic endocrine and exocrine diseases, with adjustments for age, gender, ethnicity, Townsend deprivation index, smoking, alcohol consumption, body mass index, waist circumference, hip circumference, hypertension, dyslipidemia, and gallstones.
ResultsA total of 415, 497 participants were included, among which 37, 482 developed pancreas-related diseases during follow-up. Among patients with AIDs, the proportions of those with pancreatic exocrine and endocrine diseases were significantly increased (P < 0.05). Rheumatoid arthritis [HR(95%CI): 1.438(1.161 to 1.781)], ankylosing spondylitis [HR(95%CI): 1.675(1.009 to 2.780)], ulcerative colitis [HR(95%CI): 1.335(1.037 to 1.719)], and Crohn's disease [HR(95%CI): 1.530(1.154 to 2.028)] were all associated with an increased risk of developing pancreatic exocrine diseases (all P < 0.05); additionally, rheumatoid arthritis [HR(95%CI): 1.119(1.004 to 1.248)], ulcerative colitis [HR(95%CI): 1.324(1.175 to 1.491)], systemic sclerosis [HR(95%CI): 2.08(1.355 to 3.191)], and Crohn's disease[HR(95%CI): 1.394(1.197 to 1.624)] were also associated with an increased risk of developing pancreatic endocrine diseases (all P < 0.05).
ConclusionOverall AIDs and some specific AIDs are associated with an increased risk of developing pancreatic endocrine and exocrine diseases, and early prevention of pancreatic diseases in patients with AIDs should be emphasized in clinical practice.
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表 1 伴有AIDs与无AIDs的参与者基线特征比较[n(%)][M(P25, P75)]
基线特征 分类 无AIDs组(n=443 271) 伴有AIDs组(n=8 226) P 年龄/岁 58.0(50.0, 63.0) 59.0(52.0, 64.0) < 0.001 人种(白种人) 420 846(94.9) 7 863(95.6) 0.008 性别(女性) 239 902(54.1) 5 032(61.2) < 0.001 吸烟 从不 245 702(55.4) 3 854(46.9) < 0.001 既往 151 652(34.2) 3 388(41.2) 现在 45 917(10.4) 984(12.0) 饮酒 从不 18 440(4.2) 520(6.3) < 0.001 既往 14 661(3.3) 584(7.1) 现在 410 170(92.5) 7 122(86.6) 体质量指数/(kg/m2) 26.6(24.1, 29.7) 26.9(24.1, 30.3) < 0.001 腰围/cm 89.0(80.0, 98.0) 90.0(80.0, 99.0) < 0.001 臀围/cm 102.0(97.0, 108.0) 102.0(97.0, 109.0) 0.076 汤森剥夺指数 -2.2(-3.7, 0.4) -1.9(-3.5, 1.0) < 0.001 高血压 133 728(30.2) 3 800(46.2) < 0.001 血脂异常 68 120(15.4) 1 784(21.7) < 0.001 胆结石 23 012(5.2) 908(11.0) < 0.001 总胰腺疾病 36 364(8.2) 1 118(13.6) < 0.001 胰腺外分泌疾病 7 432(1.6) 280(3.4) < 0.001 急性胰腺炎 2 849(0.6) 111(1.3) < 0.001 胰腺癌 1 749(0.4) 33(0.4) 0.925 其他胰腺外分泌疾病 2 834(0.6) 136(1.7) < 0.001 胰腺内分泌疾病 34 259(7.7) 1 078(13.1) < 0.001 糖尿病 31 438(7.1) 911(11.1) < 0.001 其他胰腺内分泌疾病 2 821(0.6) 167(2.0) < 0.001 
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表 2 AIDs与总体胰腺疾病发生风险的相关性
变量 模型1 模型2 P HR 95%CI P HR 95%CI 系统性红斑狼疮 0.005 1.605 1.157~2.225 0.895 0.978 0.705~1.357 类风湿关节炎 < 0.001 1.792 1.624~1.977 < 0.001 1.199 1.087~1.323 干燥综合征 < 0.001 1.720 1.296~2.283 0.359 1.142 0.860~1.516 系统性硬化症 < 0.001 2.645 1.772~3.946 < 0.001 2.062 1.381~3.077 肌炎 0.034 2.025 1.054~3.893 0.132 1.652 0.859~3.175 血管炎 < 0.001 1.929 1.503~2.474 0.110 1.225 0.955~1.572 强直性脊柱炎 0.007 1.446 1.107~1.888 0.838 0.973 0.745~1.270 银屑病和肠性关节炎 < 0.001 1.861 1.467~2.361 0.503 1.085 0.855~1.376 多发性硬化症 < 0.001 1.671 1.369~2.040 0.071 1.202 0.985~1.467 重症肌无力 < 0.001 2.504 1.705~3.677 0.030 1.529 1.041~2.246 自身免疫性肝炎 0.013 2.055 1.167~3.619 0.315 1.337 0.759~2.354 溃疡性结肠炎 < 0.001 1.499 1.345~1.672 < 0.001 1.347 1.208~1.502 克罗恩病 < 0.001 1.744 1.522~1.999 < 0.001 1.477 1.289~1.693 Graves病 < 0.001 1.928 1.409~2.640 0.060 1.351 0.987~1.850 自身免疫性甲状腺炎 0.479 1.127 0.707~2.096 0.929 0.976 0.566~1.681 自身免疫性溶血 0.028 2.680 1.115~6.439 0.536 1.318 0.549~3.168 特发性血小板减少 0.001 1.697 1.235~2.333 0.167 1.252 0.910~1.720 模型1: 根据招募时的年龄、性别、种族及汤森剥夺指数进行调整; 模型2: 进一步调整了吸烟、饮酒、BMI、腰围、臀围、合并高血压、血脂异常、胆结石。
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表 3 AIDs与胰腺外分泌疾病发生风险的相关性
变量 模型1 模型2 P HR 95%CI P HR 95%CI 系统性红斑狼疮 0.003 2.545 1.368~4.734 0.175 1.536 0.826~2.859 类风湿关节炎 < 0.001 2.151 1.738~2.662 < 0.001 1.438 1.161~1.781 干燥综合征 0.102 1.726 0.897~3.319 0.783 1.096 0.570~2.109 系统性硬化症 0.104 2.253 0.845~6.006 0.409 1.512 0.567~4.030 肌炎 0.184 2.560 0.640~10.237 0.695 1.319 0.330~5.276 血管炎 0.011 2.086 1.184~3.675 0.312 1.339 0.760~2.361 强直性脊柱炎 < 0.001 2.503 1.508~4.155 0.046 1.675 1.009~2.780 银屑病和肠性关节炎 0.050 1.805 0.999~3.260 0.682 1.132 0.626~2.046 多发性硬化症 0.004 1.897 1.223~2.943 0.317 1.251 0.806~1.942 重症肌无力 0.003 3.363 1.511~7.488 0.151 1.799 0.808~4.007 自身免疫性肝炎 0.394 1.826 0.457~7.302 0.986 1.012 0.253~4.051 溃疡性结肠炎 < 0.001 1.687 1.311~2.171 0.025 1.335 1.037~1.719 克罗恩病 < 0.001 2.418 1.833~3.216 0.003 1.530 1.154~2.028 Graves病 0.066 2.004 0.955~4.205 0.328 1.447 0.690~3.038 自身免疫性甲状腺炎 0.496 1.482 0.478~4.597 0.907 0.935 0.301~2.900 自身免疫性溶血 — — — — — — 特发性血小板减少 0.551 1.306 0.543~3.138 0.841 0.914 0.380~2.197 模型1: 根据招募时的年龄、性别、种族及汤森剥夺指数进行调整; 模型2: 进一步调整了吸烟、饮酒、BMI、腰围、臀围、合并高血压、血脂异常、胆结石。在自身免疫性溶血基础上患有胰腺外分泌疾病参与者过少，因此未纳入分析。
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表 4 AIDs与胰腺内分泌疾病发生风险的相关性
变量 模型1 模型2 P HR 95%CI P HR 95%CI 系统性红斑狼疮 0.053 1.443 0.996~2.090 0.530 0.888 0.613~1.286 类风湿关节炎 < 0.001 1.688 1.514~1.881 0.043 1.119 1.004~1.248 干燥综合征 0.002 1.635 1.194~2.239 0.853 1.030 0.752~1.411 系统性硬化症 < 0.001 2.675 1.744~4.103 < 0.001 2.080 1.355~3.191 肌炎 0.105 1.845 0.880~3.871 0.142 1.742 0.830~3.655 血管炎 < 0.001 1.871 1.426~2.456 0.237 1.178 0.898~1.547 强直性脊柱炎 0.117 1.274 0.941~1.724 0.319 0.857 0.633~1.161 银屑病和肠性关节炎 < 0.001 1.804 1.394~2.334 0.973 0.996 0.769~1.288 多发性硬化症 < 0.001 1.686 1.361~2.089 0.076 1.214 0.980~1.504 重症肌无力 < 0.001 2.249 1.466~3.449 0.083 1.460 0.951~2.239 自身免疫性肝炎 0.012 2.128 1.178~3.843 0.192 1.482 0.820~2.677 溃疡性结肠炎 < 0.001 1.441 1.279~1.622 < 0.001 1.324 1.175~1.491 克罗恩病 < 0.001 1.578 1.355~1.838 < 0.001 1.394 1.197~1.624 Graves病 < 0.001 1.958 1.399~2.741 0.055 1.389 0.992~1.945 自身免疫性甲状腺炎 0.713 1.123 0.604~2.088 0.936 0.975 0.525~1.813 自身免疫性溶血 0.010 3.156 1.314~7.582 0.332 1.543 0.642~3.707 特发性血小板减少 0.003 1.679 1.194~2.363 0.235 1.230 0.874~1.731 模型1: 根据招募时的年龄、性别、种族及汤森剥夺指数进行调整; 模型2: 进一步调整了吸烟、饮酒、BMI、腰围、臀围、合并高血压、血脂异常、胆结石。
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