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.     

Diabetes mellitus and risk of pancreatic cancer in China: A meta-analysis based on 26 case-control studies

AimsThe relationship between diabetes mellitus and pancreatic cancer risk from is uncertain based on the results of existing publications. The current report updated and re-evaluated the possible association between diabetes mellitus and pancreatic cancer risk in China.MethodsSix databases (PubMed, Embase, Web of Science, the Cochrane Library, the Chinese Biomedical Database, and the Chinese National Knowledge Infrastructure) were used for the literature search up to October 2017.ResultsTwenty-six case-control studies involving 7702 pancreatic cancer cases and 10186 controls were screened out. The overall summary estimate for the relationship between diabetes and pancreatic cancer was 3.69 (95% CI, 3.12–4.37). The subgroup analysis indicated positive associations among northern and southern Chinese, as well as studies with healthy population or hospital controls. In addition, the risk of developing pancreatic cancer was inversely associated with the duration of diabetes, with the highest risk of pancreatic cancer occurring among patients with diabetes <2 years. Individuals who had diabetes <2 years had a >2-fold higher risk of developing pancreatic cancer than individuals who had diabetes for 2–4 years or 5–10 years (OR, 4.92; 95% CI, 4.16–5.80 vs. OR, 1.92; 95% CI, 1.30–2.85/OR, 2.14; 95% CI, 1.49–3.09).ConclusionsThis meta-analysis strongly supports that an association exists between diabetes and an increased risk of pancreatic cancer in China, which should be confirmed with other ethnic groups.     

Diabetes mellitus and the risk of pancreatitis: A systematic review and meta-analysis of cohort studies

BackgroundDiabetes mellitus has been associated with increased risk of pancreatitis in several studies, however, not all studies have found an association. We conducted a systematic review and meta-analysis of prospective studies on diabetes mellitus and pancreatitis to clarify the association.MethodsPubMed and Embase databases were searched for studies on diabetes mellitus and pancreatitis up to 8^th of January 2020. Cohort studies that reported adjusted relative risk (RR) estimates and 95% confidence intervals (CIs) for the association between diabetes diagnosis and pancreatitis were included and summary RRs (95% CIs) were calculated using a random effects model.ResultsEight cohort studies were included in the meta-analysis, and seven of these were included in the analysis of diabetes mellitus and acute pancreatitis (14124 cases, 5.7 million participants). Comparing diabetes patients with persons without diabetes the summary RRs (95% CIs) were 1.74 (95% CI: 1.33–2.29, I² = 95%) for acute pancreatitis, 1.40 (95% CI: 0.88–2.22, I² = 0%, n = 2) for chronic pancreatitis, and 1.39 (95% CI: 1.07–1.80, I² = 54%, n = 3) for pancreatitis overall. Although there was some indication of publication bias in the analysis of acute pancreatitis this appeared to be explained by one outlying study which when excluded did not substantially alter the association. The results persisted in several subgroup and sensitivity analyses.ConclusionsThese results suggest that diabetes patients are at an increased risk of acute pancreatitis. Further studies are needed on diabetes and risk of chronic pancreatitis, pancreatitis overall and on gallstone-related and non-gallstone-related pancreatitis.     

Diabetes mellitus and risk of prostate cancer: a meta-analysis

Aims/hypothesis The association of diabetes mellitus with prostate cancer has been controversial. This study examines the strength of this association by conducting a detailed meta-analysis of the studies published in peer-reviewed literature on the subject.Methods A comprehensive search for articles published up to 2003 was performed, reviews of each study were conducted and data were abstracted. Prior to meta-analysis, the studies were evaluated for publication bias and heterogeneity. Pooled relative risk (RR) was calculated using the random- and the fixed-effects models. Subgroup and sensitivity analyses were also performed.Results We included 14 studies, published between 1971 and 2002, in the meta-analysis (five case-control studies, nine cohort studies). We found no evidence of publication bias (p=0.89) or heterogeneity among the studies (p=0.38). The association of diabetes with prostate cancer was statistically significant, both on the basis of a random-effects model (RR=0.91, 95% CI: 0.86 to 0.96), and on the basis of a fixed-effects model (RR=0.91, 95% CI: 0.88 to 0.94). When the analysis was stratified into subgroups according to study design, the association was inverse in both cohort and case-control studies, but only in the former was it statistically significant. The sensitivity analysis strengthened our confidence in the validity of this association.Conclusions/interpretation Our meta-analysis findings provide strong evidence that people with diabetes have a significant decrease in risk of developing prostate cancer. There is biological evidence to support this association.Abbreviations RR relative risk     

Diabetes mellitus and the risk of sudden cardiac death: A systematic review and meta-analysis of prospective studies

Background

Although diabetes mellitus is an established risk factor for myocardial infarction and stroke, data on the association with sudden cardiac death are less extensive and the findings have not been entirely consistent. We therefore conducted a systematic review and meta-analysis of prospective studies on diabetes mellitus and risk of sudden cardiac death.

Diabetes mellitus and the risk of abdominal aortic aneurysm: A systematic review and meta-analysis of prospective studies

Background

Diabetes mellitus has been associated with reduced risk of abdominal aortic aneurysm in a number of epidemiological studies, however, until recently little data from prospective studies have been available. We therefore conducted a systematic review and meta-analysis of prospective studies to quantify the association.

Nature and management of pancreatic mucinous cystic neoplasm (MCN): A systematic review of the literature

BackgroundThe current management of pancreatic mucinous cystic neoplasms (MCN) is defined by the consensus European, International Association of Pancreatology and American College of Gastroenterology guidelines. However, the criterion for surgical resection remains uncertain and differs between these guidelines. Therefore through this systematic review of the existing literature we aimed to better define the natural history and prognosis of these lesions, in order to clarify recommendations for future management.MethodsA systematic literature search was performed (PubMed, EMBASE, Cochrane Library) for studies published in the English language between 1970 and 2015.ResultsMCNs occur almost exclusively in women (female:male 20:1) and are mainly located in the pancreatic body or tail (93–95%). They are usually found incidentally at the age of 40–60 years. Cross-sectional imaging and endoscopic ultrasound are the most frequently used diagnostic tools, but often it is impossible to differentiate MCNs from branch duct intraductal papillary mucinous neoplasms (BD-IPMN) or oligocystic serous adenomas pre-operatively. In resected MCNs, 0–34% are malignant, but in those less than 4 cm only 0.03% were associated with invasive adenocarcinoma. No surgically resected benign MCNs were associated with a synchronous lesion or recurrence; therefore further follow-up is not required after resection. Five-year survival after surgical resection of a malignant MCN is approximately 60%.ConclusionsCompared to other pancreatic tumors, MCNs have a low aggressive behavior, with exceptionally low rates of malignant transformation when less than 4 cm in size, are asymptomatic and lack worrisome features on pre-operative imaging. This differs significantly from the natural history of small BD-IPMNs, supporting the need to differentiate mucinous cyst subtypes pre-operatively, where possible. The findings support the recommendations from the recent European Consensus Guidelines, for the more conservative management of MCNs.     

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging （MRI）/magnetic resonance cholangio pancreatography （MRCP） and computer tomography （CT） scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms （IPMN）. While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

Intraductal papillary mucinous neoplasms and other pancreatic cystic lesions

Pancreatic cystic neoplasms are being increasingly recognized, even in the absence of symptoms, in large part, due to markedly improved imaging modalities such as magnetic resonance imaging (MRI)/magnetic resonance cholangio pancreatography (MRCP) and computer tomography (CT) scanning. During the past 2 decades, better imaging of these cystic lesions has resulted in definition of different types, including pancreatic intraductal papillary mucinous neoplasms (IPMN). While IPMN represent only a distinct minority of all pancreatic cancers, they appear to be a relatively frequent neoplastic form of pancreatic cystic neoplasm. Moreover, IPMN have a much better outcome and prognosis compared to pancreatic ductal adenocarcinomas. Therefore, recognition of this entity is exceedingly important for the clinician involved in diagnosis and further evaluation of a potentially curable form of pancreatic cancer.     

Diabetes mellitus,blood glucose and the risk of atrial fibrillation: A systematic review and meta-analysis of cohort studies

Background

Diabetes and elevated blood glucose have been associated with increased risk of atrial fibrillation in a number of epidemiological studies, however, the findings have not been entirely consistent. We conducted a systematic review and meta-analysis to clarify the association.

Diabetes mellitus,blood glucose and the risk of heart failure: A systematic review and meta-analysis of prospective studies

Background and Aim

The strength of the association between diabetes and risk of heart failure has differed between previous studies and the available studies have not been summarized in a meta-analysis. We therefore quantified the association between diabetes and blood glucose and heart failure in a systematic review and meta-analysis.

Diabetes mellitus as a risk factor for gastrointestinal cancer among American veterans

AIM: To assess the risk of biliary and pancreatic cancers in a large cohort of patients with type 2 diabetes mellitus (DM).METHODS: Eligibility for this study included patients with type 2 DM (ICD-9 code 250.0) who were discharged from Department of Veteran Affairs hospitals between 1990 and 2000. Non-matched control patients without DM were selected from the same patient treatment files during the same period. Demographic information included age, sex and race. Secondary diagnoses included known risk factors based on their ICD-9 codes. By multivariate logistic regression, the occurrence of biliary and pancreatic cancer was compared between case subjects with DM and controls without DM.RESULTS: A total of 1 172 496 case and control subjects were analyzed. The mean age for study and control subjects was 65.8 ± 11.3 and 64.8 ± 12.6 years, respectively. The frequency of pancreatic cancer in subjects with DM was increased (0.9%) in comparison to control subjects (0.3%) with an OR of 3.22 (95% CI: 3.03-3.42). The incidence of gallbladder and extrahepatic biliary cancers was increased by twofold in diabetic patients when compared to controls. The OR and 95% CI were 2.20 (1.56-3.00) and 2.10 (1.61-2.53), respectively.CONCLUSION: Our study demonstrated that patients with DM have a threefold increased risk for developing pancreatic cancer and a twofold risk for developing biliary cancer.     

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.     

Italian consensus guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms

This report contains clinically oriented guidelines for the diagnostic work-up and follow-up of cystic pancreatic neoplasms in patients fit for treatment. The statements were elaborated by working groups of experts by searching and analysing the literature, and then underwent a consensus process using a modified Delphi procedure. The statements report recommendations regarding the most appropriate use and timing of various imaging techniques and of endoscopic ultrasound, the role of circulating and intracystic markers and the pathologic evaluation for the diagnosis and follow-up of cystic pancreatic neoplasms.     

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。     

The association between psoriasis and diabetes mellitus: A systematic review and meta-analysis

BackgroundPsoriasis is an immune-mediated chronic inflammatory skin disease with unknown etiology. Current findings demonstrate that psoriatic patients are at higher risk of other systemic disorders such as diabetes mellitus. The present study was conducted to evaluate the association between psoriasis and diabetes mellitus.MethodThe current study was conducted based on preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidelines. Using MeSH keywords we searched online databases of PubMed, Scopus, Web of Science, Science Direct, Embase, CINAHL, Cochrane Library, EBSCO and Google scholar search engine and the reference list of the retrieved articles until June 2018. Heterogeneity among studies was assessed using Cochran's Q test and I² index and the random effects model was used to estimate Odds Ratio (OR) and 95% confidence interval (CI). Data were analyzed using Comprehensive Meta-Analysis (CMA) software version 2.ResultsAnalysis of 38 eligible studies involving 922870 cases and 12808071 controls suggested the estimated OR to be 1.69 (95% Confidence Interval [CI]: 1.51–1.89; P < 0.001). Subgroup analysis was conducted based on study design and country of study and was significant (test for subgroup differences: P = 0.025 and P < 0.001, respectively).ConclusionsOur study indicated the significant association between psoriasis and diabetes. Therefore, psoriasis is a systemic disorder and other comorbidities should be considered in the management of patients with psoriasis.     

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。