Diabetes mellitus and gastric carcinoma: Is there an association?
ABSTRACT Diabetes mellitus (DM) has been associated with the risk of several gastrointestinal cancers including liver, pancreas, colon and rectum. However, the evidence is inconclusive for gastric adenocarcinoma (GC). In the current review, we summarize 20 population-based cohort studies that compared GC incidence and mortality between diabetic and non-diabetic population. We discuss the shared risk factors and provide qualitative and quantitative (meta-analytic) summary of the current evidence evaluating the association by high-risk subgroups. The overall risk-estimate based on all studies did not show an increased risk of GC in diabetics. However, 2 cohort studies conducted in East Asian countries, where Helicobacter pylori infection and GC rates are higher, showed a higher risk of GC in diabetics. Additionally, high plasma glucose levels in the presence of Helicobacter pylori infection increased the risk of GC by over four times, suggesting a multiplicative effect. Results from the meta-analysis show that, the risk of GC was also higher in populations with greater prevalence of type 1 DM (relative risk = 1.60), suggesting an insulin-independent carcinogenic process in this subgroup. The risk of mortality due to GC was higher in diabetics compared to non-diabetics (relative risk = 1.62). Although the overall risk estimates do not show an association between DM and GC, complex interactions between infectious, molecular, demographic and host factors may convey a higher risk in certain subgroups. Future studies should be sufficiently powered for detailed subgroup analysis to elucidate the causative and mechanistic association between DM and GC.
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ABSTRACT: This article reviews the epidemiological evidence linking diabetes and gastric cancer and discusses some of the potential mechanisms, confounders and biases in the evaluation of such an association. Findings from four meta-analyses published from 2011 to 2013 suggest a positive link, which may be more remarkable in females and in the Asian populations. Putative mechanisms may involve shared risk factors, hyperglycemia, Helicobacter pylori (H. pylori) infection, high salt intake, medications and comorbidities. Diabetes may increase the risk of gastric cancer through shared risk factors including obesity, insulin resistance, hyperinsulinemia and smoking. Hyperglycemia, even before the clinical diagnosis of diabetes, may predict gastric cancer in some epidemiological studies, which is supported by in vitro, and in vivo studies. Patients with diabetes may also have a higher risk of gastric cancer through the higher infection rate, lower eradication rate and higher reinfection rate of H. pylori. High salt intake can act synergistically with H. pylori infection in the induction of gastric cancer. Whether a higher risk of gastric cancer in patients with diabetes may be ascribed to a higher intake of salt due to the loss of taste sensation awaits further investigation. The use of medications such as insulin, metformin, sulfonylureas, aspirin, statins and antibiotics may also influence the risk of gastric cancer, but most of them have not been extensively studied. Comorbidities may affect the development of gastric cancer through the use of medications and changes in lifestyle, dietary intake, and the metabolism of drugs. Finally, a potential detection bias related to gastrointestinal symptoms more commonly seen in patients with diabetes and with multiple comorbidities should be pointed out. Taking into account the inconsistent findings and the potential confounders and detection bias in previous epidemiological studies, it is expected that there are still more to be explored for the clarification of the association between diabetes and gastric cancer.World Journal of Gastroenterology 02/2014; 20(7):1701-1711. · 2.43 Impact Factor
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ABSTRACT: Background Hyperglycemia increases the risk of gastric cancer in H. pylori-infected patients. High glucose could increase endothelial permeability and cancer-associated signaling. These suggest high glucose may affect H. pylori or its infected status.We used two strains to investigate whether H. pylori growth, viability, adhesion and CagA-phosphorylation level in the infected-AGS cells were influenced by glucose concentration (100, 150, and 200 mg/dL).ResultsThe growth curves of both strains in 200 mg/dL of glucose were maintained at the highest optimal density after 48 h and the best viability of both strains were retained in the same glucose condition at 72 h. Furthermore, adhesion enhancement of H. pylori was significantly higher in 200 mg/dL of glucose as compared to that in 100 and 150 mg/dL (p¿<¿0.05). CagA protein also increased in higher glucose condition. The cell-associated CagA and phosphorylated-CagA was significantly increased in 150 and 200 mg/dL of glucose concentrations as compared to that of 100 mg/dL (p¿<¿0.05), which were found to be dose-dependent.Conclusion Higher glucose could maintain H. pylori growth and viability after 48 h. H. pylori adhesion and CagA increased to further facilitate the enhancement of cell-associated CagA and phosphorylated CagA in higher glucose conditions.Journal of Biomedical Science 10/2014; 21(1):96. · 2.74 Impact Factor
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ABSTRACT: To investigate the association and quantify the relationship between diabetes mellitus (DM) and gastric cancer (GC) by an updated meta-analysis. The initial PubMed search identified 1233 publications. Studies not reporting GC or those not reporting actual number of GC were excluded. Twelve pertinent studies were retrieved from the PubMed database or from a manual search and considered for the meta-analysis. Pooled risk ratios and 95%CI were estimated by a random-effects model. Subgroup analysis was performed according to gender or geographical regions. Heterogeneity and publication bias were evaluated by I (2) and funnel plot analysis, respectively. DM was significantly associated with GC with a RR of 1.41 (P = 0.006) (95%CI: 1.10-1.81). Subgroup analyses revealed that both sexes showed a significant association with GC, with a greater magnitude of risk in females (RR = 1.90; 95%CI: 1.27-2.85; P = 0.002) than in males (RR = 1.24; 95%CI: 1.08-1.43; P = 0.002). In addition, the link between DM and GC was significant in East Asian DM patients (RR = 1.77; 95%CI: 1.38-2.26; P < 0.00001) but not in Western DM patients (RR = 1.23; 95%CI: 0.90-1.68; P = 0.2). There was no evidence of publication bias, but the results indicated significant heterogeneity. This updated meta-analysis has provided evidence of positive DM-GC associations. The limited information on potentially important clinical confounding factors in each study deserves further investigation.World Journal of Gastroenterology 10/2013; 19(40):6902-10. · 2.43 Impact Factor