急性胰腺炎新发糖尿病的危险因素分析及列线图模型构建

李福军 ,  张蓉 ,  方堃 ,  陈娟 ,  庄天时 ,  王超

临床肝胆病杂志 ›› 2026, Vol. 42 ›› Issue (8) : 1908 -1916.

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临床肝胆病杂志 ›› 2026, Vol. 42 ›› Issue (8) : 1908 -1916. DOI: 10.12449/JCH260824
胰腺疾病

急性胰腺炎新发糖尿病的危险因素分析及列线图模型构建

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Risk factors for post-acute pancreatitis diabetes mellitus and construction of a nomogram prediction model

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摘要

目的 分析急性胰腺炎(AP)患者新发糖尿病(PPDM-A)的危险因素,并构建列线图预测模型,为未来制订个体化治疗方案提供参考。 方法 前瞻性选取2021年6月—2025年1月徐州医科大学附属徐州市立医院收治的351例AP患者为研究对象,按照7∶3比例将患者随机分为建模组(n=246)与验证组(n=105)。根据AP患者是否发生PPDM-A,将建模组进一步分为PPDM-A组(n=86)和非PPDM-A组(n=160)。收集患者的临床资料,采用最小绝对收缩和选择算子(LASSO)回归分析筛选自变量,采用Logistic回归分析PPDM-A的影响因素,并利用R软件构建列线图模型。采用受试者操作特征曲线评估模型的区分度,使用Hosmer-Lemeshow(H-L)检验模型拟合度,校准曲线评估模型一致性;采用决策曲线分析(DCA)评估模型的临床应用价值。计量资料两组间比较采用成组t检验;计数资料两组间比较采用χ2检验。 结果 建模组246例患者中,有86例发生PPDM-A,发生率为34.96%。PPDM-A组与非PPDM-A组在年龄≥60岁(65.12% vs 40.62%)、男性(75.58% vs 55.63%)、体重指数(BMI)≥24 kg/m2(63.95% vs 37.50%)、酒精性AP(56.98% vs 36.87%)、中重度AP(54.65% vs 35.00%)、血钙[(1.46±0.35)mmol/L vs (1.89±0.37)mmol/L]、计算机体层成像严重程度指数(CTSI)评分≥4分(48.84% vs 28.75%)、随机血糖[(17.68±4.12)mmol/L vs (11.68±4.27)mmol/L]比较,差异均有统计学意义(P值均<0.05)。LASSO回归分析共筛选出8个自变量,将8个自变量进行Logistic回归分析,结果显示年龄、性别、BMI、酒精性AP、中重度AP、CTSI评分及随机血糖均是PPDM-A的危险因素(P值均<0.05),血钙为保护因素(P<0.05)。建模组的曲线下面积(AUC)为0.932(95%置信区间:0.903~0.962);H-L拟合优度检验结果为χ2=7.346(P=0.728),模型拟合的准确度较好;较准曲线显示预测概率与实际概率一致,说明一致性较好。验证组的AUC为0.835(95%置信区间:0.753~0.917),H-L拟合优度检验结果为χ2=7.014(P=0.711),模型拟合的准确度较好;较准曲线显示预测概率与实际概率一致,说明一致性较好。建模组DCA结果显示,当阈值概率在0.13~0.94时,该模型评估PPDM-A的临床价值较高。 结论 年龄、性别、BMI、酒精性AP、中重度AP、血钙、CTSI评分及随机血糖是PPDM-A的影响因素,基于上述影响因素构建的列线图模型对PPDM-A风险具有较好的预测能力,可为临床制订PPDM-A预防策略提供参考。

Abstract

Objective To investigate the risk factors for post-acute pancreatitis diabetes mellitus (PPDM-A) in patients with acute pancreatitis (AP), to construct a nomogram prediction model, and to provide a reference for the development of individualized treatment regimens. Methods A total of 351 patients with AP who were admitted to Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University from June 2021 to January 2025 were prospectively enrolled, and they were randomly divided into modeling group with 246 patients and validation group with 105 patients at a ratio of 7∶3. According to the presence or absence of PPDM-A in the patients with AP, the modeling group was further divided into PPDM-A group with 86 patients and non-PPDM-A group with 160 patients. Clinical data were collected from all patients. The least absolute shrinkage and selection operator (LASSO) regression analysis was used to determine independent variables, and a Logistic regression analysis was used to investigate the influencing factors for PPDM-A. R software was used to construct a nomogram model. The receiver operating characteristic curve was used to assess the discriminatory ability of the model, and the Hosmer-Lemeshow test was used to test the model fitting degree, and the calibration curve was used to evaluate the model consistency; and decision curve analysis (DCA) was used to assess its clinical application value. The independent-samples t test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. Results Among the 246 patients, 86 developed PPDM-A, resulting in an incidence rate of 34.96%. There were significant differences between the PPDM-A group and the non-PPDM-A group in the proportion of patients with an age of ≥60 years (65.12% vs 40.62%, P<0.05), male sex (75.58% vs 55.63%, P<0.05), a body mass index (BMI) of ≥24 kg/m2 (63.95% vs 37.50%, P<0.05), alcoholic AP (56.98% vs 36.87%, P<0.05), moderate-to-severe AP (54.65% vs 35.00%, P<0.05), or a computed tomography severity index (CTSI) score of ≥4 points (48.84% vs 28.75%, P<0.05), as well as significant differences in the levels of blood calcium (1.46±0.35 mmol/L vs 1.89±0.37 mmol/L, P<0.05) and random blood glucose (Glu) (17.68±4.12 mmol/L vs 11.68±4.27 mmol/L, P<0.05). The LASSO regression analysis obtained 8 independent variables. The Logistic regression analysis showed that age, sex, BMI, alcoholic AP, moderate-to-severe AP, CTSI score, and Glu were risk factors for PPDM-A (all P<0.05), while blood calcium was a protective factor (P<0.05). The model had an area under the ROC curve (AUC) of 0.932 (95% confidence interval [CI]: 0.903 — 0.962) in the modeling group, and the Hosmer-Lemeshow goodness-of-fit test yielded χ2=7.346 (P=0.728), the accuracy of model fitting was good; the calibration curve showed that the predicted probability was consistent with the actual probability, indicating that the consistency was good. The model had an AUC of 0.835 (95%CI: 0.753 — 0.917) in the validation group, and the Hosmer-Lemeshow goodness-of-fit test yielded χ2=7.014 (P=0.711), the accuracy of model fitting was good; the calibration curve showed that the predicted probability was consistent with the actual probability, indicating that the consistency was good. The DCA results of the modeling group showed that the model exhibited a high clinical value in evaluating PPDM-A when the threshold probability was 0.13 — 0.94. Conclusion Age, sex, BMI, alcoholic AP, moderate-to-severe AP, blood calcium, CTSI score, and Glu are influencing factors for PPDM-A. The nomogram model constructed based on the above influencing factors shows good performance in predicting the risk of PPDM-A and can thus provide a reference for developing prevention strategies for PPDM-A in clinical practice.

Graphical abstract

关键词

胰腺炎 / 糖尿病 / 危险因素 / 列线图

Key words

Pancreatitis / Diabetes Mellitus / Risk Factors / Nomogram

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李福军,张蓉,方堃,陈娟,庄天时,王超. 急性胰腺炎新发糖尿病的危险因素分析及列线图模型构建[J]. 临床肝胆病杂志, 2026, 42(8): 1908-1916 DOI:10.12449/JCH260824

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急性胰腺炎(acute pancreatitis,AP)是由多种病因激活胰酶,造成胰腺和胰周组织发生自身消化,并诱发局部炎症反应,是导致患者住院的常见消化系统疾病之一[1]。近年来,AP所致胰腺内分泌功能不全进而引发糖尿病的情况逐渐受到关注,主要是因为胰腺外分泌实质的破坏,从而引起糖尿病。此外,AP新发糖尿病(post-acute pancreatitis diabetes mellitus,PPDM-A)也会造成AP患者进展为急性重症胰腺炎,引发全身严重感染,严重威胁患者生命安全[2-3]。因此,识别影响PPDM-A的临床因素,对于制订预防策略及改善患者生活质量具有重要意义。目前,关于PPDM-A危险因素的列线图预测模型研究仍较为有限[4-5]。本研究旨在探讨PPDM-A的危险因素,并构建其列线图预测模型。

1 资料与方法

1.1 研究对象

前瞻性选取2021年6月—2025年1月本院收治的351例AP患者为研究对象,采用随机数字表法按照7∶3比例将患者随机分为建模组(n=246)与验证组(n=105)。为保证数据集划分的透明度及研究可重复性,分组过程采用R语言完成,设置随机种子set.seed(12345),以确保不同研究者在重复该分组过程中可获得完全一致的分组结果,分组后即刻验证两组样本量占比、基线资料均衡性,确保分组方案科学可靠。根据AP患者是否新发糖尿病,将建模组进一步分为PPDM-A组和非PPDM-A组。纳入标准:(1)符合AP诊断标准[6];(2)PPDM-A组患者符合糖尿病诊断标准[7];(3)临床资料完整。排除标准:(1)合并恶性肿瘤者;(2)存在免疫功能障碍者;(3)合并重要脏器衰竭者;(4)既往有糖尿病病史者;(5)既往有胰腺炎病史者。

1.2 PPDM-A诊断标准

患者既往无糖尿病病史,在初次发生AP后至少3个月确诊为糖尿病,符合以下任一项即可确诊:(1)伴有糖尿病症状,随机血糖≥11.1 mmol/L;(2)空腹血糖≥7.0 mmol/L;(3)糖化血红蛋白≥6.5%;(4)口服葡萄糖耐量试验2 h后血糖>11.1 mmol/L[7]。

1.3 观察指标及临床资料收集

比较建模组和验证组患者的临床资料,包括患者年龄、性别、体重指数(body mass index,BMI)、居住地、婚姻状况、文化程度、高血压、吸烟史、饮酒史、高尿酸血症、胆源性AP、酒精性AP、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、白蛋白、球蛋白、肌酐、血尿酸、血钙、血钾、胱抑素C、血脂肪酶、血淀粉酶、计算机体层成像严重程度指数(computed tomography severity index,CTSI)评分(主要是根据计算机体层成像影像评估胰腺形态、胰腺坏死面积和胰腺外并发症3个部分,评分为三者相加所得)[8]及随机血糖。

1.4 统计学方法

采用SPSS 25.0软件进行数据统计分析。计量资料以x¯±s表示,两组间比较采用成组t检验;计数资料两组间比较采用χ2检验。采用最小绝对收缩和选择算子(least absolute shrinkage and selection operator,LASSO)回归分析筛选自变量;采用Logistic回归分析PPDM-A的影响因素。采用R 4.5.1软件及rns程序包构建列线图模型。采用受试者操作特征曲线(receiver operating characteristic curve,ROC曲线)评估模型区分度;使用Hosmer-Lemeshow(H-L)检验模型拟合度,校准曲线评估模型的一致性;采用决策曲线分析(decision curve analysis,DCA)评估模型的临床应用价值。P<0.05为差异有统计学意义。

2 结果

2.1 建模组与验证组临床资料比较

建模组与验证组患者在年龄、性别及BMI等临床资料方面的差异均无统计学意义(P值均>0.05)(表1)。

2.2 PPDM-A组和非PPDM-A组临床资料比较

246例建模组患者中,有86例发生PPDM-A,发生率为34.96%。PPDM-A组和非PPDM-A组在年龄、性别、BMI、酒精性AP、中重度AP、血钙、CTSI评分及随机血糖方面的差异均有统计学意义(P值均<0.05)(表2)。

2.3 LASSO回归分析

以PPDM-A为因变量(PPDM-A=1,非PPDM-A=0),自变量及变量赋值方式见表3。采用R软件进行LASSO回归分析,当λ=0.034 562 4时,共筛选出8个预测因素(年龄、性别、BMI、酒精性AP、中重度AP、血钙、CTSI评分及随机血糖)(图1、2)。

2.4 PPDM-A的影响因素分析

根据LASSO回归筛选的自变量进行Logistic分析(逐步回归法,纳入标准=0.05,排除标准=0.10),结果显示,年龄、性别、BMI、酒精性AP、中重度AP、CTSI评分及随机血糖是PPDM-A的危险因素(P值均<0.05),而血钙为保护因素(P<0.05)(表4)。

2.5 PPDM-A列线图模型的构建

根据多因素分析结果构建预测模型,公式如下:P=ex/(1+ex),x=-7.372+0.062×年龄+1.808×性别+1.086×BMI+1.802×酒精性AP+0.964×中重度AP-2.255×血钙+1.101×CTSI评分+0.361×随机血糖。该模型的列线图见图3。

2.6 建模组列线图模型的验证

建模组中,列线图模型的ROC曲线下面积(area under the curve,AUC)为0.932(95%置信区间:0.903~0.962)(图4);H-L拟合优度检验结果为χ2=7.346(P=0.728)(图5),模型拟合的准确度较好;校准曲线结果显示预测概率与实际概率接近,说明一致性较好。

2.7 验证组列线图模型的验证

验证组中,列线图模型的AUC为0.835(95%置信区间:0.753~0.917)(图6);H-L拟合优度检验结果为χ2=7.014(P=0.711),模型拟合的准确度较好;校准曲线结果显示预测概率与实际概率接近,说明一致性较好(图7)。

2.8 建模组列线图模型的DCA

DCA结果显示,当阈值概率在0.13~0.94时,该模型评估PPDM-A的临床价值较高(图8)。

3 讨论

胰腺在机体新陈代谢中发挥重要作用,但胰腺炎会对代谢紊乱产生影响,发生AP后会增加机体出现代谢紊乱的风险[9-10],尤其是PPDM-A。其机制在于:胰腺发生急性炎症时,机体的胰腺组织会出现缺血、水肿及微循环障碍,对胰岛素的排泄和分泌产生影响,造成大量胰岛素细胞在短期内出现坏死,内源性胰岛素严重分泌不足,从而使患者血糖升高[11-12]。本研究PPDM-A发生率为34.96%,与江明菲等[13]研究结果(38.90%)相似,说明PPDM-A的发生率较高。因此,构建PPDM-A预测模型,对于临床早期预防具有重要意义。

本研究通过LASSO-Logistic回归分析筛选出年龄、性别、BMI、酒精性AP、中重度AP、血钙、CTSI评分及随机血糖是PPDM-A的影响因素,分析其原因如下。(1)年龄:对于年龄较大的患者来说,随着年龄增长,机体的胰腺细胞出现老化,胰岛β细胞数量减少、胰岛素分泌能力下降,引起患者随机血糖升高;AP发作时的炎症应激会进一步加重胰岛β细胞损伤,加速胰岛素分泌不足的进程,最终诱发PPDM-A[14]。(2)性别:男性相比女性更易发生糖尿病,可能与男性体型、吸烟、饮酒等因素有关。既往研究发现,男性糖尿病的发病率和病死率均显著高于女性[15],与本研究结果相似。针对年龄和性别等客观因素,临床医护人员应加强对患者的照护,进行长期随访,强化健康行为干预及疾病相关认知,提高患者的自我管理能力,延缓疾病进展。(3)BMI:BMI值越大,说明患者胰腺损伤越严重,可导致胰腺内外分泌功能异常,引起胰腺微循环障碍,进而引起血糖升高。部分患者即使治疗后胰腺功能有所恢复,但仍可能存在长期血糖稳态异常,从而增加新发糖尿病的风险[16-17]。临床应指导患者注重体重健康管理,合理健康饮食,积极锻炼,减轻体重。(4)酒精性AP:酒精及其代谢产物可直接损伤胰岛β细胞,抑制胰岛素的合成与分泌,且这种损伤具有不可逆性。长期饮酒可导致胰岛功能永久性衰退,酒精可诱导胰腺炎症反应加重,促进炎症因子释放,间接加重胰岛损伤,同时影响肝脏糖代谢,进一步升高随机血糖,易诱发糖尿病[18]。(5)中重度AP:中重度AP患者存在更严重的胰腺组织水肿、坏死,而胰岛组织与胰腺外分泌组织相互交织,胰腺实质的广泛损伤会直接累及胰岛β细胞,导致胰岛素分泌锐减;同时,中重度AP患者的全身炎症反应更为剧烈,炎症因子可通过血液循环扩散至全身,进一步抑制胰岛功能;且重症AP患者常需长期禁食,也会间接影响糖代谢,增加糖尿病的发生风险[19]。(6)血钙:血清钙离子浓度升高时可激活氯离子通道,加速腺泡细胞凋亡,从而保护细胞免受损害,保护胰腺组织。而当机体发生AP后,机体中的胰蛋白酶被激活,产生大量炎症介质及细胞因子,降低患者血清钙离子浓度。因此,临床检测其指标变化可评估PPDM-A的发生风险[20]。血钙和PPDM-A呈现“U”型关系,即血钙过低或过高均会增加PPDM-A的发生风险,血钙过低提示胰腺坏死严重,胰岛损伤不可逆;血钙过高则可能加重胰岛β细胞凋亡,进一步抑制胰岛素分泌。本研究因受样本量限制,未能充分验证这一“U”型关系,后续需扩大样本量进一步探讨。(7)CTSI评分:CTSI评分是一种可评估AP胰腺损伤程度的评分,通常超过4分则说明患者病情较为严重。CTSI评分越高,说明胰腺坏死范围越大、炎症反应越剧烈。胰岛组织多分布于胰腺实质内,胰腺实质的广泛损伤会直接破坏胰岛β细胞的结构与功能,导致胰岛素分泌不足。同时,高CTSI评分患者常合并胰腺周围渗出、感染等并发症,进一步加重全身炎症反应,间接抑制胰岛功能,从而增加糖尿病的发生风险[21]。(8)随机血糖:血糖升高时,机体细胞葡萄糖负荷增加,促进糖酵解及氧化磷酸化,产生过多过氧化物,对细胞产生毒性作用,增强氧化应激反应,并对多个脏器产生损害。当胰腺发生氧化应激时,会减少胰腺腺泡细胞数量,抑制胰岛素的合成和分泌,最终使机体血糖进一步升高并发展为PPDM-A[22]。因此,PPDM-A的发生是多因素协同作用的结果,各危险因素通过直接/间接损伤胰岛β细胞功能、加重胰岛素抵抗,最终导致血糖调节能力不可逆下降。临床医护人员需加强对高危人群的随机血糖筛查,对高风险患者进行密切随访,并通过饮食、运动、血糖监测等管理手段进行干预,以改善患者长期结局,强化疾病的早期管理,积极改善胰腺功能。

本研究所构建的列线图模型结果显示,建模组和验证组的AUC分别为0.932、0.835,且根据H-L拟合优度检验提示模型一致性良好。DCA结果显示,当阈值概率为0.13~0.94时,该列线图模型评估PPDM-A的临床应用价值较高,可协助临床医师根据影响因素及时采取预防措施,从而有效改善患者的生活质量。

综上所述,年龄、性别、BMI、酒精性AP、中重度AP、血钙、CTSI评分及随机血糖是PPDM-A的影响因素,基于上述影响因素构建的列线图模型对PPDM-A风险具有较好的预测能力,可为临床制订PPDM-A预防策略提供参考。本研究尚存在一定局限性,主要体现在样本量有限且为单中心设计,后续应扩大样本量并开展多中心研究进一步验证模型的有效性。

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基金资助

徐州市科技项目(KC21216)

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