Diabetes and gastric cancer: The potential links

Table 2 Explanations on the putative mechanisms linking diabetes and gastric cancer and the limitations of current studies

Factors	Explanations/limitations
Shared risk factors	Explanations: Diabetes and gastric cancer may share common risk factors such as obesity, insulin resistance, hyperinsulinemia and smoking Limitations: These shared risk factors are known to cause cancer. Therefore, if these shared risk factors are in play, they may also increase the risk of other types of cancer, like colorectal cancer and lung cancer. As demonstrated in some studies, the link between diabetes and gastric cancer may be independent of smoking. Evidence for such an effect in humans needs to be fortified by further studies
Hyperglycemia	Explanations: Hyperglycemia is associated with pro-inflammatory status, oxidative stress, impaired immune function and increased insulin secretion. All of these may contribute to the development of gastric cancer. Epidemiological studies conducted in Japan support hyperglycemia as a risk factor for gastric cancer, and an interaction between hyperglycemia and H. pylori infection. Such a link may also be supported by findings from in vitro studies Limitations: Confirmation of such a link in other ethnicities is necessary
H. pylori infection	Explanations: Diabetes and H. pylori infection may be mutually causative. Patients with diabetes may have a higher infection rate, a lower eradication rate, and/or a higher reinfection rate of H. pylori. On the other hand, the inflammatory process induced by H. pylori infection may also increase the risk of diabetes Limitations: Findings in epidemiological studies are controversial with regards to the higher infection rate of H. pylori in patients with diabetes. Detection bias can not be excluded because patients with diabetes may suffer from more gastrointestinal symptoms leading to the diagnosis of H. pylori infection and gastric cancer
Salt intake	Explanations: A synergistic effect between H. pylori infection and salt intake on gastric cancer is supported by recent human studies and by in vivo and in vitro studies. Patients with diabetes may consume more salt because of loss of sensitivity to taste Limitations: Patients with diabetes may also be advised to take less salt especially in those with hypertension, kidney disease or congestive heart failure. Epidemiological studies evaluating the link between salt intake and gastric cancer in patients with diabetes are lacking
Medications	Explanations: Insulin and sulfonylureas may increase the risk of cancer. On the other hand, metformin, aspirin and statin may potentially reduce the risk of gastric cancer. Patients who repeatedly use antibiotics may have a lower risk of infection with H. pylori Limitations: Research of well quality on the use of medications and gastric cancer risk is lacking
Comorbidities	Explanations: Patients with diabetes may have multiple comorbidities including obesity, hypertension, dyslipidemia, vascular complications and heart failure. All of these may affect the development of gastric cancer, either positively or negatively, through the use of medications and changes in lifestyle, salt intake, dietary components, and the metabolism of drugs Limitations: A detection bias on H. pylori infection or gastric cancer is possible in patients with multiple comorbidities. Studies clarifying such links are still lacking

H. pylori:Helicobacter pylori.