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Article(id=1241771813416538436, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241771801366299468, articleNumber=null, orderNo=null, doi=10.20043/j.cnki.MPM.202406404, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=null, receivedDate=1719244800000, receivedDateStr=2024-06-25, revisedDate=null, revisedDateStr=null, acceptedDate=null, acceptedDateStr=null, onlineDate=1773991071322, onlineDateStr=2026-03-20, pubDate=1729785600000, pubDateStr=2024-10-25, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1773991071322, onlineIssueDateStr=2026-03-20, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1773991071322, creator=13701087609, updateTime=1773991071322, updator=13701087609, issue=Issue{id=1241771801366299468, tenantId=1146029695717560320, journalId=1227665162245664772, year='2024', volume='51', issue='20', pageStart='3649', pageEnd='3840', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=null, createTime=1773991068450, creator=13701087609, updateTime=1773991676896, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1241774353457681403, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241771801366299468, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1241774353457681404, tenantId=1146029695717560320, journalId=1227665162245664772, issueId=1241771801366299468, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=3810, endPage=3815, ext={EN=ArticleExt(id=1241771814930682215, articleId=1241771813416538436, tenantId=1146029695717560320, journalId=1227665162245664772, language=EN, title=Study on the association between stress-induced hyperglycemia and the risk of new-onset diabetes after pancreatitis in acute pancreatitis patients, columnId=null, journalTitle=Modern Preventive Medicine, columnName=null, runingTitle=null, highlight=null, articleAbstract=
Objective

To investigate the relationship between stress-induced hyperglycemia in acute pancreatitis (AP) patients and the risk of developing new-onset diabetes after pancreatitis.

Methods

This study selected patients with acute pancreatitis (AP) who had no prior history of diabetes and were hospitalized in the Department of Gastroenterology at Nanjing Drum Tower Hospital, affiliated with Nanjing University, 2015-2019. New-onset diabetes after pancreatitis was diagnosed based on established criteria. The relationship between stress-induced hyperglycemia upon admission and the risk of developing new-onset diabetes was assessed using the COX proportional hazards model. Stratified analyses were conducted based on gender, age, education level, place of residence, marital status, smoking history, admission diagnosis, Body Mass Index (BMI), history of pancreatic necrosis/abscess, and severity of the condition.

Results

This study included a total of 1258 participants. The follow-up incidence of diabetes was 28.3%. Patients who experienced stress-induced hyperglycemia upon admission had a higher risk of developing new-onset diabetes compared to those with normal blood glucose levels (HR=1.40, 95%CI:1.06-1.85). Subgroup analysis indicated that patients who were elderly(HR=2.01, 95%CI:1.19-2.12), male(HR=1.17, 95%CI:1.03-2.35), from rural areas(HR=1.37, 95%CI:1.24-1.53),had a history of smoking(HR=1.25, 95%CI:1.14-1.38), had a history of pancreatic necrosis/abscess(HR=1.34，95%CI:1.07-1.98), BMI≥28 kg/m ? (HR=2.33, 95%CI:1.57-4.553), or had moderate to severe pancreatitis(HR=1.45, 95%CI:1.27-2.58; HR=1.23, 95%CI:1.06-1.93), had a greater risk of developing new-onset diabetes if they experienced stress-induced hyperglycemia.

Conclusion

Stress hyperglycemia at admission is associated with an increased risk of new-onset diabetes after pancreatitis. Effective glucose management in high-risk AP patients with stress hyperglycemia may help reduce the risk of developing new-onset diabetes.

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目的

探究发生应激性高血糖的急性胰腺炎（Acute Pancreatitis,AP）患者与胰腺炎后新发糖尿病风险之间的关系。

方法

本研究选取2015—2019年于南京大学附属鼓楼医学院消化内科住院既往无糖尿病病史的AP患者作为研究对象，基于胰腺炎后新发糖尿病诊断标准判定新发糖尿病，使用COX比例风险模型评估入院应激性高血糖与新发糖尿病风险之间的关系。按性别、年龄、文化程度、居住地、婚姻情况、吸烟史、入院诊断、身体质量指数（Body Mass Index, BMI）、既往胰腺坏死/脓肿史及病情严重程度分组进行亚组分析。

结果

本研究共纳入1 258名研究对象。随访糖尿病发生率为28.3%，入院发生应激性高血糖患者相比于正常血糖者有较高的糖尿病发病风险（HR=1.40，95%CI:1.06~1.85）。亚组分析显示老年（HR=2.01，95%CI:1.19~2.12）、男性（HR=1.17，95%CI:1.03~2.35）、居住农村（HR=1.37，95%CI:1.24~1.53）、有吸烟史（HR=1.25，95%CI:1.14~1.38）、有胰腺坏死/脓肿病史（HR=1.34，95%CI:1.07~1.98）、BMI≥28 kg/m2（HR=2.33，95%CI:1.57~4.55）以及中重度胰腺炎（HR=1.45，95%CI:1.27~2.58；HR=1.23，95%CI:1.06~1.93）的患者发生应激性高血糖有更大的糖尿病发病风险。

结论

AP患者入院应激性高血糖与胰腺炎后新发糖尿病的发病风险有关，应加强发生应激性高血糖的高危AP患者的早期筛查与血糖管理，有助于降低新发糖尿病的发病风险。

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李雯，E-mail：
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田恬（1999—），女，硕士在读，研究方向：胰腺炎相关研究工作

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Annals of Internal Medicine, 2023, 176(8): 1037-1046., articleTitle=Achievement of guideline-recommended targets in diabetes care inChina : a nationwide cross-sectional study, refAbstract=null), Reference(id=1241771829967262691, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, doi=null, pmid=null, pmcid=null, year=2024, volume=193, issue=5, pageStart=685, pageEnd=694, url=null, language=null, rfNumber=[24], rfOrder=29, authorNames=Luo YX, Liu ZR, Luo JW, journalName=American Journal of Epidemiology, refType=null, unstructuredReference=Luo YX, Liu ZR, Luo JW, et al. BMI trajectories in late middle age, genetic risk, and incident diabetes in older adults: evidence from a 26-Year longitudinal study[J]. American Journal of Epidemiology, 2024, 193(5): 685-694., articleTitle=BMI trajectories in late middle age, genetic risk, and incident diabetes in older adults: evidence from a 26-Year longitudinal study, refAbstract=null)], funds=[Fund(id=1241771825118647144, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, awardId=82373068, language=CN, fundingSource=国家自然科学基金(82373068), fundOrder=null, country=null), Fund(id=1241771825231893358, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, awardId=SJCX24_0851, language=CN, fundingSource=江苏省研究生实践创新计划项目(SJCX24_0851), fundOrder=null, country=null), Fund(id=1241771825374499698, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, awardId=2024-B301, language=CN, fundingSource=南京鼓楼医院护理科研项目(2024-B301), fundOrder=null, country=null)], companyList=[AuthorCompany(id=1241771819527639650, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, xref=1., ext=[AuthorCompanyExt(id=1241771819536028260, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, companyId=1241771819527639650, language=EN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=Nanjing University of Chinese Medicine Nursing College, Nanjing, Jiangsu 210023, China), AuthorCompanyExt(id=1241771819548611173, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, companyId=1241771819527639650, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=1.南京中医药大学护理学院，江苏 南京 210023)]), AuthorCompany(id=1241771819687023218, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, xref=2., ext=[AuthorCompanyExt(id=1241771819691217523, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, companyId=1241771819687023218, language=CN, country=null, province=null, city=null, postcode=null, companyName=null, departmentName=null, remark=2.南京大学医学院附属鼓楼医院消化内科，江苏 南京)])], figs=[ArticleFig(id=1241771824107819835, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=EN, label=Table 1, caption=

Characteristics of the study subjects at baseline

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变量人数应激性高血糖组（n=383）正常血糖组（n=875）t/χ2值P值
年龄（岁,）1 25855.45±16.5448.65±14.6316.949<0.001
性别[n(%)]54.859<0.001
男669264（68.9）405（46.3）
女589119（31.1）470（53.7）
居住地[n(%)]5.1800.023
农村457157（41.0）300（34.3）
城市801226（59.0）575（65.7）
婚姻情况[n(%)]4.9170.032
已婚1 045323（84.3）722（82.5）
未婚/离异/丧偶21360（15.7）153（17.5）
文化程度[n(%)]3.3400.048
高中以下572189（49.3）383（43.8）
高中及以上686194（50.7）492（56.2）
吸烟[n(%)]17.446<0.001
是514190（49.6）324（37.0）
否744193（50.4）551（63.0）
饮酒[n(%)]6.6870.010
是20578（20.4）127（14.5）
否1 053305（79.6）748（85.5）
BMI（kg/m2，）1 25826.35±4.5525.27±4.088.631<0.001
入院诊断[n(%)]14.926<0.001
脂源性564203（53.0）361（41.3）
胆源性523137（35.8）386（44.1）
其他17143（11.2）128（14.6）
胰腺坏死/脓肿史[n(%)]58.954<0.001
是348198（51.7）150（17.1）
否910185（48.3）725（82.9）
疼痛（分，）1 2581.18±0.560.56±0.034.1390.038
CRP(109/L,）1 25872.65±40.8426.55±28.1412.337<0.001
病情程度[n(%)]79.953<0.001
轻度58388（23.0）495（56.6）
中度32797（25.3）230（26.3）
重度348198（51.7）150（17.1）
入院血糖水平（mmol/L，）1 25811.49±4.198.90±3.708.050<0.001
中性粒细胞（109/L，）1 2584.8±1.153.55±1.125.6510.018
糖尿病发病率[n(%)]356202（52.7）154（17.6）16.193<0.001
), ArticleFig(id=1241771824229454655, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=CN, label=表1, caption=

研究对象的基线特征

, figureFileSmall=null, figureFileBig=null, tableContent=
变量人数应激性高血糖组（n=383）正常血糖组（n=875）t/χ2值P值
年龄（岁,）1 25855.45±16.5448.65±14.6316.949<0.001
性别[n(%)]54.859<0.001
男669264（68.9）405（46.3）
女589119（31.1）470（53.7）
居住地[n(%)]5.1800.023
农村457157（41.0）300（34.3）
城市801226（59.0）575（65.7）
婚姻情况[n(%)]4.9170.032
已婚1 045323（84.3）722（82.5）
未婚/离异/丧偶21360（15.7）153（17.5）
文化程度[n(%)]3.3400.048
高中以下572189（49.3）383（43.8）
高中及以上686194（50.7）492（56.2）
吸烟[n(%)]17.446<0.001
是514190（49.6）324（37.0）
否744193（50.4）551（63.0）
饮酒[n(%)]6.6870.010
是20578（20.4）127（14.5）
否1 053305（79.6）748（85.5）
BMI（kg/m2，）1 25826.35±4.5525.27±4.088.631<0.001
入院诊断[n(%)]14.926<0.001
脂源性564203（53.0）361（41.3）
胆源性523137（35.8）386（44.1）
其他17143（11.2）128（14.6）
胰腺坏死/脓肿史[n(%)]58.954<0.001
是348198（51.7）150（17.1）
否910185（48.3）725（82.9）
疼痛（分，）1 2581.18±0.560.56±0.034.1390.038
CRP(109/L,）1 25872.65±40.8426.55±28.1412.337<0.001
病情程度[n(%)]79.953<0.001
轻度58388（23.0）495（56.6）
中度32797（25.3）230（26.3）
重度348198（51.7）150（17.1）
入院血糖水平（mmol/L，）1 25811.49±4.198.90±3.708.050<0.001
中性粒细胞（109/L，）1 2584.8±1.153.55±1.125.6510.018
糖尿病发病率[n(%)]356202（52.7）154（17.6）16.193<0.001
), ArticleFig(id=1241771824346895176, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=EN, label=Table 2, caption=

Univariate Cox Proportional Hazards Regression Model Analysis of New-Onset Diabetes After Pancreatitis

, figureFileSmall=null, figureFileBig=null, tableContent=
变量βSEWald χ2P值HR（95%CI）
性别0.310.126.6800.0101.36（1.08~1.73）
年龄0.690.1139.359<0.0011.99（1.38~2.88）
文化程度0.400.148.1570.0041.49（1.11~2.01）
居住地0.120.101.4410.2301.13（0.93~1.37）
婚姻0.100.140.5110.4751.11（0.84~1.46）
吸烟0.710.1141.712<0.0012.03（1.63~2.53）
饮酒0.250.152.7790.0961.28（0.86~1.90）
入院诊断0.450.1410.3600.0011.57（1.18~2.09）
应激性高血糖0.740.1145.358<0.0012.10（1.54~2.85）
胰腺坏死/脓肿0.710.1141.714<0.0012.03（1.64~2.51）
病情程度0.230.105.2900.0211.26（1.04~1.52）
BMI0.320.127.1100.0081.38（1.09~1.75）
疼痛0.400.1211.1130.0011.49（1.18~1.87）
CRP0.560.1031.359<0.0011.75（1.38~2.22）
), ArticleFig(id=1241771824493695820, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=CN, label=表2, caption=

胰腺炎后新发糖尿病发病的单因素Cox比例风险回归模型分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量βSEWald χ2P值HR（95%CI）
性别0.310.126.6800.0101.36（1.08~1.73）
年龄0.690.1139.359<0.0011.99（1.38~2.88）
文化程度0.400.148.1570.0041.49（1.11~2.01）
居住地0.120.101.4410.2301.13（0.93~1.37）
婚姻0.100.140.5110.4751.11（0.84~1.46）
吸烟0.710.1141.712<0.0012.03（1.63~2.53）
饮酒0.250.152.7790.0961.28（0.86~1.90）
入院诊断0.450.1410.3600.0011.57（1.18~2.09）
应激性高血糖0.740.1145.358<0.0012.10（1.54~2.85）
胰腺坏死/脓肿0.710.1141.714<0.0012.03（1.64~2.51）
病情程度0.230.105.2900.0211.26（1.04~1.52）
BMI0.320.127.1100.0081.38（1.09~1.75）
疼痛0.400.1211.1130.0011.49（1.18~1.87）
CRP0.560.1031.359<0.0011.75（1.38~2.22）
), ArticleFig(id=1241771824619524945, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=EN, label=Table 3, caption=

Multivariate Cox Proportional Hazards Regression Model Analysis of New-Onset Diabetes After Pancreatitis

, figureFileSmall=null, figureFileBig=null, tableContent=
模型HR(95%CI)P值
模型12.10(1.70~2.60)<0.001
模型21.82(1.40~2.37)<0.001
模型31.40(1.06~1.85)0.018
), ArticleFig(id=1241771824711799638, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=CN, label=表3, caption=

胰腺炎后新发糖尿病发病的多因素Cox比例风险回归模型分析

, figureFileSmall=null, figureFileBig=null, tableContent=
模型HR(95%CI)P值
模型12.10(1.70~2.60)<0.001
模型21.82(1.40~2.37)<0.001
模型31.40(1.06~1.85)0.018
), ArticleFig(id=1241771824850211675, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=EN, label=Table 4, caption=

Subgroup analysis of the association between stress hyperglycemia and new-onset diabetes mellitus

, figureFileSmall=null, figureFileBig=null, tableContent=
变量HR（95%CI）P值P交互
年龄（岁）0.311
<601.14（0.85~1.52）0.370
≥602.01（1.19~2.12）<0.001
性别0.288
男1.17（1.03~2.35）<0.001
女1.02（0.77~1.35）0.628
文化程度0.551
高中以下1.22（1.11~1.34）0.001
高中及以上1.33（1.11~2.38）<0.001
居住地0.070
城市1.22（0.94~1.58）0.133
农村1.37（1.24~1.53）<0.001
婚姻情况0.166
已婚1.24（1.15~1.34）<0.001
未婚/离异/丧偶1.28（1.05~1.68）<0.001
吸烟史0.499
吸烟1.25（1.14~1.38）<0.001
不吸烟1.04（0.90~1.45）0.367
入院诊断0.108
脂源性1.36（1.25~1.51）<0.001
胆源性1.13（1.03~1.26）<0.001
其他1.09（1.02~1.43）0.024
胰腺坏死/脓肿0.581
是1.34（1.07~1.98）<0.001
否1.05（0.88~1.79）0.668
病情程度0.153
轻度1.02（0.69~1.23）0.673
中度1.45（1.27~2.58）<0.001
重度1.23（1.06~1.93）<0.001
BMI（kg/m2）0.130
<241.07（0.65~1.75）0.687
24~27.91.44（1.15~2.79）0.102
≥282.33（1.57~4.55）<0.001
), ArticleFig(id=1241771824971846495, tenantId=1146029695717560320, journalId=1227665162245664772, articleId=1241771813416538436, language=CN, label=表4, caption=

应激性高血糖与新发糖尿病相关性的亚组分析

, figureFileSmall=null, figureFileBig=null, tableContent=
变量HR（95%CI）P值P交互
年龄（岁）0.311
<601.14（0.85~1.52）0.370
≥602.01（1.19~2.12）<0.001
性别0.288
男1.17（1.03~2.35）<0.001
女1.02（0.77~1.35）0.628
文化程度0.551
高中以下1.22（1.11~1.34）0.001
高中及以上1.33（1.11~2.38）<0.001
居住地0.070
城市1.22（0.94~1.58）0.133
农村1.37（1.24~1.53）<0.001
婚姻情况0.166
已婚1.24（1.15~1.34）<0.001
未婚/离异/丧偶1.28（1.05~1.68）<0.001
吸烟史0.499
吸烟1.25（1.14~1.38）<0.001
不吸烟1.04（0.90~1.45）0.367
入院诊断0.108
脂源性1.36（1.25~1.51）<0.001
胆源性1.13（1.03~1.26）<0.001
其他1.09（1.02~1.43）0.024
胰腺坏死/脓肿0.581
是1.34（1.07~1.98）<0.001
否1.05（0.88~1.79）0.668
病情程度0.153
轻度1.02（0.69~1.23）0.673
中度1.45（1.27~2.58）<0.001
重度1.23（1.06~1.93）<0.001
BMI（kg/m2）0.130
<241.07（0.65~1.75）0.687
24~27.91.44（1.15~2.79）0.102
≥282.33（1.57~4.55）<0.001
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急性胰腺炎患者的应激性高血糖与胰腺炎后新发糖尿病发病风险关联研究
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田恬 1, 2 , 吴兆荣 1, 2 , 王倩 2 , 张舒 2 , 李雯 1, 2
现代预防医学 | 临床与预防 2024,51(20): 3810-3815
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现代预防医学 | 临床与预防 2024, 51(20): 3810-3815
急性胰腺炎患者的应激性高血糖与胰腺炎后新发糖尿病发病风险关联研究
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田恬1, 2, 吴兆荣1, 2, 王倩2, 张舒2, 李雯1, 2
作者信息
  • 1.南京中医药大学护理学院，江苏 南京 210023
  • 2.南京大学医学院附属鼓楼医院消化内科，江苏 南京

    • 田恬（1999—），女，硕士在读，研究方向：胰腺炎相关研究工作

通讯作者:

李雯，E-mail：
Study on the association between stress-induced hyperglycemia and the risk of new-onset diabetes after pancreatitis in acute pancreatitis patients
Tian TIAN1, 2, Zhao-rong WU1, 2, Qian WANG2, Shu ZHANG2, Wen LI1, 2
Affiliations
  • Nanjing University of Chinese Medicine Nursing College, Nanjing, Jiangsu 210023, China
出版时间: 2024-10-25 doi: 10.20043/j.cnki.MPM.202406404
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摘要
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目的

探究发生应激性高血糖的急性胰腺炎（Acute Pancreatitis,AP）患者与胰腺炎后新发糖尿病风险之间的关系。

方法

本研究选取2015—2019年于南京大学附属鼓楼医学院消化内科住院既往无糖尿病病史的AP患者作为研究对象，基于胰腺炎后新发糖尿病诊断标准判定新发糖尿病，使用COX比例风险模型评估入院应激性高血糖与新发糖尿病风险之间的关系。按性别、年龄、文化程度、居住地、婚姻情况、吸烟史、入院诊断、身体质量指数（Body Mass Index, BMI）、既往胰腺坏死/脓肿史及病情严重程度分组进行亚组分析。

结果

本研究共纳入1 258名研究对象。随访糖尿病发生率为28.3%，入院发生应激性高血糖患者相比于正常血糖者有较高的糖尿病发病风险（HR=1.40，95%CI:1.06~1.85）。亚组分析显示老年（HR=2.01，95%CI:1.19~2.12）、男性（HR=1.17，95%CI:1.03~2.35）、居住农村（HR=1.37，95%CI:1.24~1.53）、有吸烟史（HR=1.25，95%CI:1.14~1.38）、有胰腺坏死/脓肿病史（HR=1.34，95%CI:1.07~1.98）、BMI≥28 kg/m2（HR=2.33，95%CI:1.57~4.55）以及中重度胰腺炎（HR=1.45，95%CI:1.27~2.58；HR=1.23，95%CI:1.06~1.93）的患者发生应激性高血糖有更大的糖尿病发病风险。

结论

AP患者入院应激性高血糖与胰腺炎后新发糖尿病的发病风险有关，应加强发生应激性高血糖的高危AP患者的早期筛查与血糖管理，有助于降低新发糖尿病的发病风险。

应激性高血糖  /  急性胰腺炎  /  糖尿病  /  Cox比例风险回归模型
Objective

To investigate the relationship between stress-induced hyperglycemia in acute pancreatitis (AP) patients and the risk of developing new-onset diabetes after pancreatitis.

Methods

This study selected patients with acute pancreatitis (AP) who had no prior history of diabetes and were hospitalized in the Department of Gastroenterology at Nanjing Drum Tower Hospital, affiliated with Nanjing University, 2015-2019. New-onset diabetes after pancreatitis was diagnosed based on established criteria. The relationship between stress-induced hyperglycemia upon admission and the risk of developing new-onset diabetes was assessed using the COX proportional hazards model. Stratified analyses were conducted based on gender, age, education level, place of residence, marital status, smoking history, admission diagnosis, Body Mass Index (BMI), history of pancreatic necrosis/abscess, and severity of the condition.

Results

This study included a total of 1258 participants. The follow-up incidence of diabetes was 28.3%. Patients who experienced stress-induced hyperglycemia upon admission had a higher risk of developing new-onset diabetes compared to those with normal blood glucose levels (HR=1.40, 95%CI:1.06-1.85). Subgroup analysis indicated that patients who were elderly(HR=2.01, 95%CI:1.19-2.12), male(HR=1.17, 95%CI:1.03-2.35), from rural areas(HR=1.37, 95%CI:1.24-1.53),had a history of smoking(HR=1.25, 95%CI:1.14-1.38), had a history of pancreatic necrosis/abscess(HR=1.34，95%CI:1.07-1.98), BMI≥28 kg/m ? (HR=2.33, 95%CI:1.57-4.553), or had moderate to severe pancreatitis(HR=1.45, 95%CI:1.27-2.58; HR=1.23, 95%CI:1.06-1.93), had a greater risk of developing new-onset diabetes if they experienced stress-induced hyperglycemia.

Conclusion

Stress hyperglycemia at admission is associated with an increased risk of new-onset diabetes after pancreatitis. Effective glucose management in high-risk AP patients with stress hyperglycemia may help reduce the risk of developing new-onset diabetes.

Stress hyperglycemia  /  Acute pancreatitis  /  Diabetes mellitus  /  Cox proportional hazards regression model
田恬, 吴兆荣, 王倩, 张舒, 李雯. 急性胰腺炎患者的应激性高血糖与胰腺炎后新发糖尿病发病风险关联研究. 现代预防医学, 2024 , 51 (20) : 3810 -3815 . DOI: 10.20043/j.cnki.MPM.202406404
Tian TIAN, Zhao-rong WU, Qian WANG, Shu ZHANG, Wen LI. Study on the association between stress-induced hyperglycemia and the risk of new-onset diabetes after pancreatitis in acute pancreatitis patients[J]. Modern Preventive Medicine, 2024 , 51 (20) : 3810 -3815 . DOI: 10.20043/j.cnki.MPM.202406404
正文
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急性胰腺炎是消化科常见的危重症疾病之一，全球范围内发病率约为34～80人每10万人每年，在我国和欧美各国均呈逐年上升趋势[1]，造成重大医疗经济负担。由于胰腺是调节血糖主要器官，部分AP患者在入院时即出现高血糖[2-3]，这种现象甚至伴随整个治疗过程，被称为应激性高血糖。近年来应激性高血糖被认为是危重疾病幸存者发生不良结局的关键危险因素，在AP领域也逐渐被研究[4-5]，有研究显示应激性高血糖与AP短期临床结局如胰腺脓肿密切相关，同时也与AP器官衰竭密切相关[6]，可作为识别AP短期不良临床结局的指标[7]。然而，目前关于AP引起的应激性高血糖与胰腺炎后新发糖尿病之间的关联少有报道。本研究旨在探讨应激性高血糖与胰腺炎后新发糖尿病之间的关联性，以期为临床早期准确识别和管理胰腺炎后新发糖尿病的高危患者提供科学依据。
1　资料与方法
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1.1　研究对象
本研究采用前瞻性队列设计，最长观察期限为9年。本研究的数据均来自于南京大学附属鼓楼医学院的住院病案系统，选取2015年１月到 2019年12月间于该院住院的急性胰腺炎病人为研究对象。随访从2015年1月开始至2023年12月结束。研究对象的纳排标准如下，纳入标准：（1）根据亚特兰大诊断标准（RAC）[8]被诊断为AP的患者；（2）研究对象年龄≥18岁；（3）既往无糖尿病史的患者。排除标准：（1）缺乏血糖等主要检测指标；（2）随访调查失访或死亡。本研究已获得南京大学附属鼓楼临床医学院伦理委员会批准[2023-679-01]，参与该项研究的所有患者或其法定代理人签署了书面知情同意书。
1.2　资料收集
基于南京大学附属鼓楼医学院住院病案系统，提取研究对象2015—2019年间首次住院时的血糖、年龄、受教育程度、居住地、婚姻、吸烟史、饮酒史、BMI、入院诊断、疼痛、C反应蛋白（C-reactive protein，CRP）、中性粒细胞、胰腺脓肿/坏死病史等数据。患者出院后即开展胰腺炎后新发糖尿病的随访。
1.3　应激性高血糖定义
本研究以应激性高血糖为自变量。应激性高血糖定义为非糖尿病和糖尿病患者的血糖（Blood glucose,BG）分别≥10.00 mmol/L或≥16.67 mmol/L，与胰岛素治疗状态无关[6]。
1.4　随访及事件定义
随访前对研究人员进行统一培训，在患者出院后定期进行电话或门诊复查随访，收集新发糖尿病患者的情况。以研究对象出院后第一天为随访起点，新发DM、死亡或至随访结束（2023年12月31日）为随访终点。胰腺炎后新发糖尿病的诊断标准[9]：既往无糖尿病病史，在胰腺炎后血糖值达到诊断糖尿病标准的基础上，主要标准（必须符合）：（1）存在胰腺外分泌功能不全（通过单克隆粪弹力蛋白酶-1检测）；（2） 存在胰腺病理改变（胰腺超声内镜检查、磁共振成像、CT发现异常）；（3）不存在1型糖尿病（T1DM）相关的自身免疫抗体；次要标准：（1）胰岛β细胞功能受损；（2）没有明显的胰岛素抵抗（如稳态模型胰岛素抵抗指数（HOMA-IR）检测）；（3）存在肠促胰素（胰高血糖素样肽1（GLP-1）等）分泌受损；（4）血脂溶性维生素浓度降低；（5）伴可被胰酶纠正的脂肪泻。依据患者入院血糖情况将患者分为应激性高血糖组和正常血糖组。
1.5　统计学分析
本研究使用R 4.2软件进行统计分析。本研究中分类变量以频数（百分比）表示，组间比较采用卡方检验或Fisher确切概率法。对于计数变量，如果变量满足正态分布采用表示，组间比较采用t检验；若变量为非正态分布，则采用M（QR）表示，组间比较采用秩和检验。采用Cox比例风险回归模型分析应激性高血糖与胰腺炎后新发糖尿病发病之间的关联，估计风险比（HR）和 95%置信区间（95% CI）。检验水准α=0.05。
2　结果
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2.1　研究对象的基线特征
经纳排标准后共1 258例AP患者被纳入研究，研究对象中男性669名（53.2%），女性589名（46.8%），应激性高血糖组383名患者（30.4%），正常血糖组875名患者（69.6%）。应激性高血糖组和正常血糖组在年龄、性别、居住地、婚姻状况、文化程度、吸烟、饮酒、BMI、诊断、CRP、胰腺坏死/脓肿病史、病情程度、糖尿病发病率之间分布差异具有统计学意义（P<0.05）。见表1。
2.2　糖尿病发生率
1 258名研究对象的中位随访时间为3.7年，研究终止时共有356名AP患者发生新发糖尿病，发病率为28.3%。应激性高血糖组202名患者发生糖尿病，发病率为52.7%，正常血糖组154名患者发生糖尿病，发生率为17.6%。
2.3　应激性高血糖与胰腺炎后糖尿病发病关联性的影响因素分析
2.3.1　单因素分析
以是否新发糖尿病（赋值：是=1，否=0）为因变量，结合文献检索和临床有可能影响新发糖尿病发病的因素：年龄（赋值：≥60岁=1，<60岁=0）、性别（赋值：男=1，女=0）、文化程度（赋值：高中及以上=1，高中以下=0）、居住地（赋值：城市=1，农村=0）、婚姻情况（赋值：已婚=1，未婚/离异/丧偶=0）、吸烟史（赋值：是=1，否=0）、饮酒史（赋值：是=1，否=0）、入院诊断（赋值：脂源性=1，其他诊断=0）、应激性高血糖（赋值：实测值）、疼痛（赋值：实测值）、BMI（赋值：实测值）、CRP（赋值：实测值）、胰腺坏死/脓肿史（赋值：是=1，否=0））病情程度（赋值：轻度=1，其他=0）为自变量进行单因素Cox比例风险回归模型分析，结果显示，性别、年龄、文化程度、吸烟史、入院诊断、应激性高血糖、疼痛、BMI、CRP、胰腺坏死/脓肿史及病情程度对新发糖尿病有影响（P<0.05），结果见表2。
2.3.2　多因素Cox比例风险回归模型分析
以新发糖尿病情况（发生=1，未发生=0）为因变量，以入院应激性高血糖为自变量，以单因素分析筛选出的变量为协变量，进行多因素 Cox 回归分析，构建回归模型：模型１：不纳入其他协变量；模型２：以年龄、性别作为协变量；模型３：在模型２基础上加入文化程度、吸烟史、入院诊断、疼痛、BMI、CRP、胰腺坏死/脓肿史及病情程度作为协变量。结果发现，当应激性高血糖为连续变量时，在调整其他混杂因素后应激性高血糖为糖尿病发病的危险因素（HR=1.40，95%CI:1.06~1.85)。见表3。
2.4　亚组分析
进一步按性别、年龄、文化程度、居住地、婚姻情况、吸烟史、入院诊断、既往胰腺坏死/脓肿史、BMI及病情严重程度进行亚组分析。结果显示，应激性高血糖与新发糖尿病的关联在老年、男性、居住农村、有吸烟史、有胰腺坏死/脓肿病史、BMI≥28 kg/m2以及中重度胰腺炎的患者中更明显，但各亚组中差异均无统计学意义（P均≥0.05）见表4。
3　讨论
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本研究采用前瞻性队列研究方法，探讨AP患者入院发生应激性高血糖和胰源性糖尿病发病之间的关联。调整后的Cox比例风险模型提示入院发生应激性高血糖会增加胰腺炎后糖尿病的发病风险。该研究为AP患者出院后新发糖尿病的早期预警提供了新的指标。
最近一项系统评价显示，在欧美国家15%的个体在AP首次发作后12个月内发生新诊断的糖尿病，并且随着时间的推移风险会增加[10]，在本研究中发现28.30%AP患者会并发新发糖尿病，发病率高于上述研究，进一步验证了前述研究的结果。经过大量文献分析阅读，少有研究直接探讨AP患者应激性高血糖与新发糖尿病之间的关系。然而，多项研究发现[11-13]，胰腺炎的严重程度、病因、胰腺坏死、非酒精性脂肪肝病、BMI和年龄均是新发糖尿病的危险因素。这些研究均为本研究的开展及分析提供了间接帮助。此外，AP患者入院发生应激性高血糖与胰腺炎后新发糖尿病的关联机制也被广泛讨论[14-15]，应激状态下胰岛素反向调节激素分泌增加，而胰岛素分泌相对减少，导致脂肪分解和蛋白分解增强，肝脏葡萄糖生成增多。同时，胰腺急性炎症时，胰腺组织水肿、缺血，出现微循环障碍，影响胰岛素的分泌和排泄，当大量胰岛细胞短期内坏死时，会导致内源性胰岛素分泌严重不足，进而导致患者血糖升高。尽管患者在得到恰当的诊疗后胰腺功能逐渐恢复，高血糖症状逐渐减退，但部分患者的胰腺功能并不能完全恢复，这导致他们的血糖稳态发生持久改变，从而增加新发糖尿病的发生风险。
亚组分析结果显示，AP患者应激性高血糖与新发糖尿病之间的关联在老年、男性、农村、有吸烟史、有胰腺脓肿/坏死史者、BMI≥28 kg/m2以及中重度胰腺炎的患者中更明显。首先，随着年龄的增长，胰腺细胞逐渐老化，导致胰岛素分泌能力下降，患者血糖升高，进而易导致糖尿病的发生[16]；第二，男性相较于女性更容易发生糖尿病，可能与男性体型、吸烟饮酒等危险因素有关，既往有研究表明，男性糖尿病的患病率和死亡率均高于女性[17]；第三，农村人口与城市人口相比因医疗资源分布及疾病认知等原因，不良健康状况的发生率较高[18-19]，本研究结果也与上述研究结果一致；第四，对于AP患者来说，胰腺功能本身就有不同程度的受损，吸烟会引发微循环收缩，进而加重胰腺功能的损害[20]，即使经过积极的治疗，但吸烟仍然是引发糖尿病的一个重要危险因素之一；第五，发生胰腺坏死/脓肿以及中重度胰腺炎的患者，其胰腺组织的广泛被破坏，胰岛细胞和外分泌腺体的功能被严重影响，因此发生糖尿病的风险更高，这与李冰青[21]和Zhi[10]的研究结果一致；最后，随着BMI的增加，糖尿病的患病风险也会随之增加。多项2型糖尿病（T2DM）研究表明，BMI与糖尿病之间存在密切联系[22-24]。在本研究中，胰腺炎后糖尿病也表现出相似的风险趋势。
综上所述，急性胰腺炎患者发生应激性高血糖对患者新发糖尿病存在一定的关联作用，警示医护人员在临床工作中应加强对高危人群的血糖管理和筛查。针对中重度胰腺炎、胰腺坏死和脓肿的患者，临床应进行多学科合作，强化疾病早期治疗的效能，尽可能的将疾病的严重程度降到最低，积极改善胰腺功能，从而降低胰源性糖尿病的发病率；对于患者的年龄、性别以及区域等客观因素，医护人员应开展延续治疗和照护，对患者进行长期随访，强化患者健康行为和疾病认知，提升患者的自我管理能力和血糖水平的观察，延缓疾病的进程。本研究还存在一些不足。首先，本研究数据来自单中心医疗机构，样本量不具完全说服力，因此研究结果还需在多中心大样本中进一步验证。其次，由于糖化血红蛋白不是AP患者入院常规检查项目，这部分数据缺失导致未能观察到长期血糖变化水平与糖尿病发病风险的关联。最后，尽管纳入了尽可能多的协变量，但仍有未测量的混杂因素未调整。
基金
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  • 国家自然科学基金(82373068)
  • 江苏省研究生实践创新计划项目(SJCX24_0851)
  • 南京鼓楼医院护理科研项目(2024-B301)
文献
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doi: 10.20043/j.cnki.MPM.202406404
  • 接收时间：2024-06-25
  • 首发时间：2026-03-20
  • 出版时间：2024-10-25
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  • 收稿日期：2024-06-25
基金
国家自然科学基金(82373068)
江苏省研究生实践创新计划项目(SJCX24_0851)
南京鼓楼医院护理科研项目(2024-B301)
作者信息
    1.南京中医药大学护理学院，江苏 南京 210023
    2.南京大学医学院附属鼓楼医院消化内科，江苏 南京

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