150例糖尿病患者胰腺外分泌功能检测及相关因素分析

目的探讨糖尿病患者胰腺外分泌功能不全的发生情况及其相关因素。方法选取2009年3月至2010年6月于第四军医大学西京医院内分泌科就诊的糖尿病患者150例,分为1型糖尿病组（T1DM,23例）、2型糖尿病组（T2DM,127例）,对照组为来我院健康体检者及我科医护人员共48人。记录糖尿病患者的年龄、性别、体质指数（BMI）、病程、糖尿病微血管病变发生情况、糖化血红蛋白（HbAle）等指标。收集受试者24h内排出的粪便,应用酶联免疫吸附实验（ELISA）法测定粪便中粪弹性蛋白酶（FE）的含量,对所有受试者的胰腺外分泌功能进行评估。率的比较采用X2检验或Fisher精确概率法。结果1型糖尿病患者、2型糖尿病患者及对照组粪便FE含量差异有统计学意义[分别为（394±237）比（502±194）比（576±170）μg／g,F=6．93,P〈0．01]。以FE〈200μg／g作为胰腺外分泌功能不全的判断标准,结果显示30．4％（7／23）的T1DM患者及7．9％（10／127）的T2DM患者存在胰腺外分泌功能不全,与对照组（0）相比,差异有统计学意义（Fisher检验P〈0．05）。以是否存在胰腺外分泌功能不全对糖尿病患者进行分组分析,结果显示两组间年龄、性别、BMI、病程、胰岛素治疗与否、糖尿病微血管病变发生情况、稳态模型胰岛素分泌指数（HOMA-B）、空腹胰岛素、餐后2h胰岛素及HbAlc等差异均无统计学意义（均P〉0．05）。结论本研究提示与健康对照相比,T1DM和他DM患者胰腺外分泌功能不全的发生率普遍较高。     

继发于胰腺癌的胰腺外分泌功能不全的研究进展

目前国际上对胰腺外分泌功能不全的诊断和治疗标准尚未完善,胰腺外科医师对继发于胰腺癌的胰腺外分泌功能不全常常忽视或错误估计,使得胰腺外分泌功能不全未得到充分治疗,严重影响了胰腺癌患者的生存质量。对胰腺癌患者胰腺外分泌功能不全的发病机制、典型症状、诊断方法、不同胰腺癌阶段的胰酶替代治疗等方面的最新研究进展进行了归纳总结,分析认为胰酶替代治疗能显著改善不同疾病阶段胰腺癌患者的生存质量。     

Pancreatic exocrine function in patients with type 1 and type 2 diabetes mellitus

Reduced exocrine pancreatic function has been observed in a high percentage of patients with type 1 diabetes in the past. There are only few data for type 2 diabetes available and they are contradictory. In this study we investigated exocrine pancreatic function in 105 controls and 114 with type 1 or type 2 diabetes mellitus by means of an indirect test (faecal elastase-1 concentration). This test has good sensitivity and specificity for moderate and severe pancreatic insufficiency as compared to the gold standard. Reduced faecal elastase-1 concentrations were found in 56.7% of type 1 patients, 35% of type 2 patients and 18.1% of the controls. Elastase-1 concentrations did not correlate with alcohol consumption, diabetes duration or diabetes therapy. The data found for type 1 patients correspond to those reported in earlier studies. The results for type 2 diabetics show that exocrine pancreatic function is also impaired in a high percentage in this group of patients. Pathogenic concepts to explain these findings as consequences of diabetes complications or insulin deficiency are still under debate. Observations from autopsies and the data of the controls in this study suggest that chronic pancreatitis might be a common problem. In consequence, diabetes secondary to exocrine disease could be much more frequent than believed so far. Received: 8 September 1999 / Accepted: 16 November 2000     

Importance of pancreatic exocrine dysfunction in patients with type 2 diabetes: A randomized crossover study

Background

Levels of faecal elastase-1 (FE-1), a marker of exocrine pancreatic function, are lower in patients with type 2 diabetes than without diabetes. We aimed to investigate the association between FE-1 and nutritional status, gastrointestinal symptoms, and lipid absorption.

Exocrine pancreatic insufficiency in long-term follow-up after curative gastric resection with D2 lymphadenectomy: A cross-sectional study

BackgroundExocrine pancreatic insufficiency (EPI) can be a problem following gastrectomies. This study aimed to reveal the EPI prevalence and its possible causes in gastric cancer patients that underwent subtotal or total gastrectomy, with completed oncological treatments, and with long-term disease-free survival success. Additionally, we also sought to determine whether there were any relations between EPI and blood biomarkers, weight change, malnutrition parameters, and quality of life after gastrectomy.MethodsA total of 69 gastric cancer patients whose oncological treatments had already been completed, with a minimum follow-up period of 16 months, were included in the study. Fecal samples were taken from all patients for the Fecal Elastase-1 Test, and patients were stratified into three groups based on the results: low (<100 μg/g), moderate (100–200 μg/g), and normal (>200 μg/g). These results were compared with patients’ clinical characteristics, blood nutrition biomarkers, Maastricht indexes (MI), Bristol stool scale, and Gastrointestinal Quality of Life Index (GIQLI) scores.ResultsFE-1 levels were low in 33 (47.8%) of the patients, moderate in 11 (15.9%), and normal in 25 (36.2%). The rate of patients receiving chemoradiotherapy (CRT) in the low FE-1 group was higher than the normal FE-1 and moderate FE-1 groups (P < 0.001 and P = 0.012, respectively). The serum total protein and lipase levels were lower in the low FE-1 group than in the normal FE-1 group (P = 0.023 and P < 0.001, respectively). When compared to the normal FE-1 group, the MI score of the low FE-1 group was higher (P = 0.018). The low FE-1 group had lower GIQLI gastrointestinal symptom scores than the normal FE-1 group (P = 0.046).ConclusionsDuring long-term follow-up, EPI can be seen in more than half of patients with gastric cancer after curative gastrectomy. Radiotherapy as an adjunct to adjuvant treatment in the postoperative period is considered a serious risk factor for EPI development. EPI contributes to malnutrition development after gastrectomy and negatively affects the patients’ quality of life, especially in terms of gastrointestinal symptoms.     

Prevalence of exocrine pancreatic insufficiency in patients with chronic pancreatitis without follow-up. PANCR-EVOL Study

Background/objectives

Exocrine pancreatic insufficiency (EPI) is an important complication of chronic pancreatitis (CP). Guidelines recommend to rule out EPI in CP, to detect those patients who would benefit from pancreatic enzyme replacement therapy. The aim of this study was to evaluate the prevalence of EPI in patients with CP without follow-up in the last 2 years and to describe their nutritional status and quality of life (QoL).

Relationship between the severity of diabetes mellitus and pancreatic exocrine dysfunction in rats

The relationship between the severity of diabetes mellitus and pancreatic exocrine function was investigated in rats made diabetic by injecting 3 different doses of streptozotocin (30, 45 or 60 mg/kg body weight). The expected correlation was obtained between the dose of streptozotocin and degree of elevation of blood glucose and decrease in pancreatic insulin content. Pancreatic amylase content of the diabetic rats was less than that of control rats and was in parallel with less values in pancreatic insulin content. On the other hand, trypsinogen content of diabetic rats was greater than that of control. Basal and caerulein-stimulated flow rates of pancreatic juice and protein output were similar in the control and in all 3 groups of diabetic rats. In contrast, there was a graded response of amylase and trypsinogen, depending upon the content of each enzyme in the pancreas. Both basal and caerulein-stimulated amylase outputs from diabetic rat pancreas were significantly reduced in parallel with the severity of diabetic state, but were similar to those from the control rats when related to the total pancreatic content. The present findings indicate that pancreatic exocrine dysfunction in diabetes mellitus is closely related to the severity of the disease, but the secretory dynamics in the perfused pancreas are not altered.     

Pancreatic exocrine insufficiency,diabetes mellitus and serum nutritional markers after acute pancreatitis

AIM: To investigate impairment and clinical significance of exocrine and endocrine pancreatic function in patients after acute pancreatitis (AP).METHODS: Patients with AP were invited to participate in the study. Severity of AP was determined by the Atlanta classification and definitions revised in 2012. Pancreatic exocrine insufficiency (PEI) was diagnosed by the concentration of fecal elastase-1. An additional work-up, including laboratory testing of serum nutritional markers for determination of malnutrition, was offered to all patients with low levels of fecal elastase-1 FE. Hemoglobin A1c or oral glucose tolerance tests were also performed in patients without prior diabetes mellitus, and type 3c diabetes mellitus (T3cDM) was diagnosed according to American Diabetes Association criteria.RESULTS: One hundred patients were included in the study: 75% (75/100) of patients had one attack of AP and 25% (25/100) had two or more attacks. The most common etiology was alcohol. Mild, moderately severe and severe AP were present in 67, 15 and 18% of patients, respectively. The mean time from attack of AP to inclusion in the study was 2.7 years. PEI was diagnosed in 21% (21/100) of patients and T3cDM in 14% (14/100) of patients. In all patients with PEI, at least one serologic nutritional marker was below the lower limit of normal. T3cDM was more frequently present in patients with severe AP (P = 0.031), but was also present in some patients with mild and moderately severe AP. PEI was present in all degrees of severity of AP. There were no statistically significantly differences according to gender, etiology and number of AP attacks.CONCLUSION: As exocrine and endocrine pancreatic insufficiency can develop after AP, routine follow-up of patients is necessary, for which serum nutritional panel measurements can be useful.     

胰腺癌伴糖尿病的蛋白质组学分析

目的 应用蛋白质组学方法 分析胰腺癌伴或不伴糖尿病的差异蛋白质,试图阐明糖尿病在胰腺癌发生、发展过程中的分子机制.方法 研究标本分为四组:胰腺癌组及其癌旁组织组,伴有糖尿病的胰腺癌组及其癌旁组织组,每组5份.利用二维电泳和基质辅助激光解析飞行时间质谱(MALDI-TOF/TOF MS/MS)技术研究四组间的蛋白表达差异.Western印迹法对巨噬细胞加帽蛋白(CapG)在癌组织中的表达进行验证.结果 在胰腺癌伴糖尿病组,有7个蛋白表达明显上调(P＜0.05),而在其他三组间的表达则差异无统计学意义(P＞0.05),这些蛋白参与了细胞运动、能量代谢、氧化应激等,其中CapG蛋白可能参与了这类患者的癌细胞浸润及转移过程.结论 该研究初步支持糖尿病参与胰腺癌进展的假说.     

Three-dimensional remnant pancreatic volume ratio indicates postoperative pancreatic exocrine insufficiency in pancreatic cancer patients after distal pancreatectomy

BackgroundPancreatectomy may cause serious pancreatic exocrine insufficiency (PEI), which can lead to some nutritional problems, including new-onset diabetes mellitus (DM) or non-alcoholic fatty liver disease (NAFLD). Recent studies have reported that remnant pancreatic volume (RPV) significantly influences postoperative PEI. However, the specific correlation between RPV and postoperative PEI remains unclear. Here, we compare various pre-, peri-, and postoperative risk factors in a retrospective cohort to address whether preoperatively measured RPV is a predictor of postoperative PEI in pancreatic cancer patients after distal pancreatectomy (DP).MethodsSixty-one pancreatic cancer patients who underwent DP were retrospectively enrolled. Pancreatic volume was measured using preoperative 3D images, which simulated the actual intraoperative pancreatic parenchymal volume. We obtained the 3D-measured RPV and resected pancreatic volume. We calculated the ratio of the RPV to the total pancreatic volume and then divided the cohort into high- and low-RPV ratio groups based on a cut-off value (>0.35, n = 37 and ≤ 0.35, n = 24). Using multivariate analysis, the RPV ratio as well as pre-, peri- and postoperative PEI risk factors were independently assessed.ResultsThe multivariate analysis revealed that a low RPV ratio (odds ratio [OR], 5.911; p = 0.001), a hard pancreatic texture (OR, 3.313; p = 0.023) and TNM stage III/IV (OR, 3.515; p = 0.031) were strong predictors of the incidence of PEI.ConclusionsThe present study indicates that the RPV ratio is an additional useful predictor of postoperative nutrition status in pancreatic cancer patients.     

Occurrence of exocrine pancreatic insufficiency in patients with advanced neuroendocrine tumors treated with somatostatin analogs

BackgroundAlthough exocrine pancreatic insufficiency (EPI) has been described in patients with neuroendocrine neoplasia (NEN) treated with somatostatin analogs (SSAs), its role in the therapeutic management of these patients is not well established.AimTo determine the frequency of EPI in patients with NEN long-term treated with SSAs.MethodsThis is a prospective single-center study evaluating 35 patients treated with SSAs for >12 months due to unresectable/advanced nonpancreatic well-differentiated NEN. Clinical evaluation, biochemical parameters, and fecal elastases 1 (FE-1) were assessed to diagnose EPI.ResultsA total of 7 patients (20%) had EPI, given the presence of abdominal symptoms and a median FE-1 value of 180 mcg/g stool (150–198). No patient had severe EPI, defined as FE-1 < 100 mcg/g stool. Elevated glycated Hb levels were a significant predictor for developing EPI (OR 4.81, p = 0.01). No significant difference in terms of duration of SSA treatment was observed between patients with or without EPI diagnosed (84 months and 72 months, respectively; p = 0.950).ConclusionsMild-moderate EPI is a relatively common condition in patients receiving long-term treatment with SSAs. Specific clinical and biochemical evaluations, including FE-1, should be planned in these patients to diagnose this relevant condition early, which may deteriorate quality of life and cause malnutrition.     

糖尿病与胰腺癌的关系探讨

目的探讨糖尿病与胰腺癌的关系。方法采用病例对照研究的方法将吉林大学中日联谊医院2000-01-01—2004-05-31期间收治的147例胰腺癌患者和同期住院的294例非肿瘤患者,按照美国糖尿病学会(ADA)1997年糖尿病诊断标准新建议分为糖尿病组和非糖尿病组,分析糖尿病对胰腺癌患病率的影响。结果合并糖尿病者患胰腺癌的OR值为27.26(P<0.05),其中男29.56,女25.29,性别间比较差异无显著性意义。糖尿病病程<2年者患胰腺癌的OR值为23.98,病程2～5年者患胰腺癌的OR值为17.04,病程>5年者患胰腺癌的OR值为33.32(P均<0.05)。肿瘤发生部位与糖尿病之间无明显相关性(P>0.05)。结论糖尿病患者中胰腺癌的发病率明显增加,2型糖尿病可能是胰腺癌的首发症状,对病程<2年的"糖尿病新患者",尤其是无糖尿病家族史者,应当注意排查胰腺癌。对病程>2年的糖尿病患者,随着糖尿病病程增加,患病危险性增加,而在不同性别糖尿病患者之间患胰腺癌的风险差异无显著性意义。     

Screening for pancreatic exocrine insufficiency in patients with diabetes mellitus

OBJECTIVES: Fecal elastase 1 (E1) is a relatively sensitive and specific indirect test of pancreatic exocrine function. Despite the high functional reserve of the pancreas, it is recognized that a significant proportion of diabetic patients may also have a deficit of the exocrine function. The aim of this study was to screen patients with diabetes mellitus (DM) for pancreatic exocrine insufficiency. METHODS: A total of 80 patients were enrolled in this prospective study, including 42 patients with DM and 38 nondiabetic controls. Exclusion criteria were as follows: age >75 yr; alcohol intake >40 g/day; intake of orlistat or acarbose; and history of diarrhea, pancreatitis, GI surgery, immunodeficiency, or cancer. All patients underwent the same study protocol, which included clinical evaluation, determination of fecal E1, plain x-rays of the abdomen, and abdominal ultrasound. An immunoenzymatic method (ScheBoTech, Wettenburg, Germany) was used for E1 determination. Diagnosis of pancreatic insufficiency was established for a fecal E1 <200 microg/g. RESULTS: The DM and control groups were comparable regarding age (62 +/- 10 yr vs 56 +/- 10 yr), sex (18 men and 24 women vs 15 men and 23 women), and proportion of patients with excess weight (50% vs 42%). Patients had DM diagnosed for 11.5 +/- 8 yr, with structural changes of the pancreas detected on ultrasound in three cases and calcifications in one case. There was no relationship between E1 determination <200 microg/g and the duration or the type of therapy for DM. Fifteen patients (36%) in the DM group had a fecal E1 <200 microg/g, compared with two patients (5%) in the control group (p < 0.05). In the DM group (n = 42), 11 patients with excess weight presented a fecal E1 <200 microg/g, whereas four patients with a BMI <25 presented this result (p < 0.05). CONCLUSIONS: Pancreatic exocrine insufficiency occurs more frequently in diabetic patients than in controls. Diabetic individuals with excess weight (BMI >25) may be at increased risk for underlying exocrine pancreatic insufficiency.     

C5b-9 and Interleukin-6 in Chronic Hepatitis C: Surrogate Markers Predicting Short-term Response to Interferon Alpha-2b

Background: Available data and our observations suggest that elevated levels of interleukin (IL)-6 and -10 and some complement parameters may be associated with a poor response to IFN alpha. We evaluated how baseline levels of C5b-9, IL-6, and IL-10 influence the outcome of IFN alpha treatment. Methods: Fifty-one patients with established chronic hepatitis C were enrolled and treated with IFN alpha-2b. Before and after a 12-week-IFN-treatment (3 MU or 5 MU tiw) serum levels of IL-6, IL-10, C5b-9 and RNA of hepatitis C virus (HCV) were assessed. Sera of 46 sex- and age-matched, healthy blood donors served as control. Results: While two-thirds of patients was considered 'responder', 14 patients had no significant decrease either in HCV RNA or in ALT levels. In the responder's group lower baseline levels of IL-6 and C5b-9 were found than those in the `non-responder' group. As a result of IFN therapy HCV RNA and C5b-9 levels significantly decreased. While the serum concentration of IL-6 increased during the follow-up period, regarding IL-10, no change was observed. In patients with 'low' baseline levels of C5b-9 (&lt;2053 ng/ml) IFN alpha resulted in a significantly (P = 0.0005) higher decrease in HCV RNA level. Regarding `low' IL-6 values (&lt;1.47 pg/ml) similar but somewhat less significant (P = 0.0039) difference was found if the change of HCV RNA was investigated. The odds ratio of patients with low IL-6 and/or C5b-9 to responding to IFN alpha treatment was almost 10 times (CI: 9.1 (1.8-50.9)) higher as compared with patients without 'low' levels of these parameters. Conclusion: Our data suggest that serum level(s) of IL-6 and/or C5b-9 taken prior to the initiation of IFN treatment may serve as surrogate marker(s) in evaluating patients with chronic hepatitis C whether to get IFN alpha in monotherapy or to consider having combination therapy in the form of IFN alpha-ribavirin.     

胰腺癌与糖尿病的流行病学研究

目的 探讨胰腺癌与糖尿病的流行病学关系.方法 收集1997年至2007年间收治的220例胰腺癌病例,以同期非消化系统、非肿瘤及非代谢异常类的300例患者作为对照组.比较两组糖尿病的发病率、糖尿病病程与胰腺癌的关系;比较胰腺癌组内糖尿病患者及血糖正常者在性别、年龄、肿瘤部位、肿瘤分化程度等方面的差异.结果 胰腺癌组和对照组糖尿病发病率分别为33.2%和9.7%.差异显著(P<0.05).胰腺癌组糖尿病病程<2年与≥10年者的比例分别为78.1%(57/73)和9.6%(7/73),显著高于对照组的62.1%(18/29)和6.9%(2/29),两组比较有统计学差异(χ2=46.15,P<0.01,OR=6.07;χ2=4.72,P<0.01,OR=4.90);胰腺癌组糖尿病病程2～<5年及5～<10年者比例与对照组无显著差异.胰腺癌组内糖尿病患者和非糖尿病患者性别、年龄、肿瘤部位比较差异无显著性,但糖尿病者肿瘤分化以乳头状或高分化腺癌为主,而无糖尿病者肿瘤以低分化腺癌为主.结论 糖尿病与胰腺癌关系密切,可能是胰腺癌的临床表现之一,也可能是胰腺癌的危险因素.     

胰腺癌与糖尿病关系的临床流行病学研究

目的探讨胰腺癌与糖尿病的流行病学关系。方法收集1991年至2004年间收治的508例胰腺癌病例;由同期非消化系统、非肿瘤及非激素代谢异常类的770例病例组成对照组。比较胰腺癌组内糖尿病患者及血糖正常者在性别、年龄、肿瘤部位、肿瘤分化程度方面的差异,并分层分析与对照组的差异。结果病例组内有和无糖尿病者性别、年龄无差异。不同胰腺癌部位及分化程度者糖尿病比例也无差异。病例组与对照组总体糖尿病发病率差异显著(33.465比8.83%,P<0.01,相对危险度=5.19),分层分析显示:糖尿病病程<2年者与>10年者的比例两组间差异有统计学意义(P<0.01,相对危险度=5.25;P<0.01,相对危险度=7.71)。结论糖尿病与胰腺癌之间有密切关系,可能是胰腺癌的早期临床表现之一,也可能是胰腺癌的危险因素。     

糖尿病与胰腺癌关系的临床分析

目的　分析 47例胰腺癌合并糖尿病的临床和病理学特征 ,初步探讨糖尿病与胰腺癌之间的关系。方法　对胰腺癌合并糖尿病及同期收治的未合并糖尿病的胰腺癌患者进行回顾性对比分析。结果　 (1)胰腺癌合并糖尿病的患者 ,占本研究中胰腺癌的 2 5 % ;(2 )两组患者均主要发生于中老年人 ,以男性多见 ,主要临床表现为上腹痛、黄疸 ;(3)两组患者胰腺癌大小、部位、胰外浸润或远处转移以及肿瘤切除率无显著性差异 ;(4 )病理学检查糖尿病组以乳头状或高分化腺癌多见 ,非糖尿病组以中、低分化腺癌多见 ;(5 )糖尿病先于胰腺癌诊断者占 19.2 % ,与胰腺癌同时诊断者占 80 .8%。结论　 (1)糖尿病可能是胰腺癌的危险因素之一 ;(2 )对中老年糖尿病患者宜常规行胰腺B超检查 ,定期随访 ,以期早期诊断 ,及时治疗 ,对改善其预后十分重要     

Metformin is associated with reduced risk of pancreatic cancer in patients with type 2 diabetes mellitus: A systematic review and meta-analysis

Aims

Recent epidemiological studies indicated that use of metformin might decrease the risk of various cancers among patients with type 2 diabetes mellitus (T2DM). However, its influence on pancreatic cancer was controversial. Therefore, we did a meta-analysis of currently available observational studies on the issue.

Methods

We did a PubMed and ISI Web of Science search for observational articles. The pooled relative risk (RR) was estimated using a random-effect model. Heterogeneity was evaluated using I² statistic. Subgroup analysis was performed to explore the source of heterogeneity and confirm the overall estimates. Publication bias was also examined.

Results

The analysis included 11 articles (13 studies) comprising 10 cohort studies and 3 case–control studies. Use of metformin was associated with a significant lower risk of pancreatic cancer [RR 0.63, 95% confidence internal (CI) 0.46–0.86, p = 0.003]. In a total 11 subgroup analyses, 5 provided the consistent result with pooled effect estimates of overall analysis. No publication bias was detected by Begg's (Z = −0.79, p = 0.428) and Egger's test (t = −0.92, p = 0.378).

Conclusions

From present observational studies, use of metformin appears to be associated with a reduced risk of pancreatic cancer in patients with T2DM. Further investigation is needed.     

Summary and recommendations from the Australasian guidelines for the management of pancreatic exocrine insufficiency

AimBecause of increasing awareness of variations in the use of pancreatic exocrine replacement therapy, the Australasian Pancreatic Club decided it was timely to re-review the literature and create new Australasian guidelines for the management of pancreatic exocrine insufficiency (PEI).MethodsA working party of expert clinicians was convened and initially determined that by dividing the types of presentation into three categories for the likelihood of PEI (definite, possible and unlikely) they were able to consider the difficulties of diagnosing PEI and relate these to the value of treatment for each diagnostic category.Results and conclusionsRecent studies confirm that patients with chronic pancreatitis receive similar benefit from pancreatic exocrine replacement therapy (PERT) to that established in children with cystic fibrosis. Severe acute pancreatitis is frequently followed by PEI and PERT should be considered for these patients because of their nutritional requirements. Evidence is also becoming stronger for the benefits of PERT in patients with unresectable pancreatic cancer. However there is as yet no clear guide to help identify those patients in the ‘unlikely’ PEI group who would benefit from PERT. For example, patients with coeliac disease, diabetes mellitus, irritable bowel syndrome and weight loss in the elderly may occasionally be given a trial of PERT, but determining its effectiveness will be difficult. The starting dose of PERT should be from 25,000–40,000 IU lipase taken with food. This may need to be titrated up and there may be a need for proton pump inhibitors in some patients to improve efficacy.