急性胰腺炎、高脂血症及糖尿病酮症酸中毒三联征患者的临床分析及基因测序  

Clinical analysis and gene sequencing of patients with the triad of acute pancreatitis,hypertriglyceridemia and diabetic ketoacidosis

作　　者：李璐[1,2] 刘黎 王世伟[2] 徐仁应 朱长清 陆晓晔[2] LI Lu;LIU Li;WANG Shiwei;XU Renying;ZHU Changqing;LU Xiaoye(Department of Clinical Nutrition,Renji Hospital,Shanghai Jiaotong University School of Medicine,Shanghai,200127,China;Department of Emergency,Renji Hospital,Shanghai Jiaotong University School of Medicine)

机构地区：[1]上海交通大学医学院机构附属仁济医院临床营养科,上海200127 [2]上海交通大学医学院附属仁济医院急诊科,上海200127

出　　处：《临床急诊杂志》2025年第2期114-120,共7页Journal of Clinical Emergency

基　　金：上海市科学技术委员会科研计划项目(No:15DZ1941307);上海市卫生健康委员会科研项目(No:20244Y0139)。

摘　　要：目的:探讨急性胰腺炎(acute pancreatitis,AP)合并高甘油三酯血症(hypertriglyceridemia,HTG)和糖尿病酮症酸中毒(diabetic ketoacidosis,DKA)三联征(AP+HTG+DKA)的临床特征及基因背景,以指导临床诊疗。方法:回顾性分析2016-2023年仁济医院急诊科收治的479例AP患者,以是否合并HTG和糖尿病(diabetes mellitus,DM)分为合并脂糖代谢紊乱和无脂糖代谢紊乱AP患者,比较两组临床特点。再将合并脂糖代谢紊乱的AP患者以是否合并DKA分为DKA三联征组(AP+HTG+DKA)和非DKA三联征组(AP+HTG+DM),比较两组临床特点。最后经过知情同意选取部分AP+HTG+DKA患者行全基因组外显子测序。结果:479例AP患者中,合并脂糖代谢紊乱的AP患者共139例(29.02%)。31例DKA三联征组患者与108例非DKA三联征组患者相比有以下特点:更年轻[平均(33.65±8.29)岁],不健康饮食比例更高(64.52%),既往糖尿病比例更高(77.42%),重症胰腺炎比例更高(58.06%),糖化血红蛋白更高[(11.20±3.19)%],血清总三碘甲状腺原氨酸(serum total triiodothyronine,TT3)水平更低[(0.73±0.23)nmol/L],血清总甲状腺素(serum total thyroxine,TT4)水平更低[(62.79±13.10)nmol/L],血清游离三碘甲状腺原氨酸(free triiodothyronine,FT3)水平更低[(2.33±0.62)nmol/L],差异有统计学意义(P<0.05)。15例AP+HTG+DKA患者经过知情同意后行全基因组外显子测序,在血脂相关基因LIPI、EPHX2、LPL、CREB3L3、GALNT2、MTTP、C5AR2、TTC39B、ANGPTL3、CYP27A1此10个基因以及血糖相关基因APPL1、PPP1R3A、GCKR、HNF1A、INS、INSR、WFS1、VEGFA此8个基因上均发现了变异。结论:AP+HTG+DKA好发中青年男性,常伴不健康饮食,既往DM和重症胰腺炎患者比例更多,糖化血红蛋白更高,TT3、TT4和FT3更低,存在血脂血糖相关基因变异可能与发病相关。Objective To investigate the clinical features and genetic background of acute pancreatitis(AP)complicated with hypertriglyceridemia(HTG)and diabetic ketoacidosis(DKA)triad(AP+HTG+DKA)to guide clinical diagnosis and treatment.Methods AP patients admitted to the Emergency Department of Renji Hospital from 2016 to 2023 were retrospectively analyzed.According to the presence or absence of complicated with HTG and diabetes mellitus(DM),AP patients were divided into AP with lipid and glucose metabolism disorders and AP without lipid and glucose metabolism disorders,and the clinical characteristics of the two groups were compared.AP patients with lipid and glucose metabolism disorders were further divided into DKA triad patients(AP+HTG+DKA)and non-DKA triad patients(AP+HTG+DM)according to whether they had DKA.The clinical characteristics of the two groups were compared as well.Finally,after informed consent,some AP+HTG+DKA patients were selected for whole exome sequencing.Results A total of 479 AP patients were included in the study.There were 139 AP patients(29.02%)with lipid and glucose metabolism disorders.The 31 AP+HTG+DKA patients had the following characteristics compared with the 108 AP+HTG+DM patients:younger,average(33.65±8.29)years,higher proportion of unhealthy diet(64.52%),higher proportion of severe pancreatitis(77.42%),higher proportion of severe pancreatitis(58.06%),higher glycosylated hemoglobin([11.20±3.19]%),lower serum total triiodothyronine(TT3)levels([0.73±0.23]nmol/L),lower serum total thyroxine(TT4)levels([62.79±13.10]nmol/L),and lower serum free triiodothyronine(FT3)level([2.33±0.62]nmol/L),the difference was statistically significant(P<0.05).Fifteen AP+HTG+DKA patients underwent whole-genome exon sequencing after informed consent.Mutations were found in 10 lipid-related genes,LIPI,EPHX2,LPL,CREB3L3,GALNT2,MTTP,C5AR2,TTC39B,ANGPTL3,and CYP27A1,and in 8 glucose-related genes,APPL1,PPP1R3A,GCKR,HNF1A,INS,INSR,WFS1,and VEGFA.Conclusion AP+HTG+DKA is prone to occur in young and middle-aged men,

关 键 词：急性胰腺炎 高甘油三酯血症 糖尿病酮症酸中毒 临床特征 基因测序 

分 类 号：R576[医药卫生—消化系统]