The Role of Type 2 Diabetes in Pancreatic Cancer

Abstract

The incidence of type 2 diabetes mellitus (T2DM) and its potential complications, such as cancers, are increasing worldwide at an astounding rate. There are many factors such as obesity, diabetes, alcohol consumption, and the adoption of sedentary lifestyles that are driving pancreatic cancer (PC) to become one of the leading causes of cancer mortality in the United States. PC is notorious for its generic symptoms and late-stage presentation with rapid metastasis. The connection between T2DM and the risk of PC development is multifaceted and complex. Some of the proposed theories reveal that chronic inflammation, insulin resistance, hyperinsulinemia, hyperglycemia, and abnormalities in the insulin and insulin-like growth factor axis (IGF) contribute to the disease association between these two conditions. This literature review aims to highlight relevant studies and explore the molecular mechanisms involved in the etiology of diabetes and its impact on PC development, as well as the role of anti-diabetic agents on PC. Despite extensive studies, the exact interaction between T2DM and PC remains obscure and will need further investigation. According to current knowledge, there is a substantial link between diabetes, obesity, and dietary patterns in the development and progression of PC. Consequently, focusing our efforts on preventive measures by reducing modifiable risk factors remains the most effective strategy to reduce the risk of PC at this time. Antidiabetic drugs can have various effects on the occurrence and prognosis of PC with metformin offering a clear benefit of inhibiting PC and insulin increasing the risk of PC. The development of future novel therapies will require a deeper knowledge of the triggering mechanisms and interplay between these two disease states.

Prognostic significance of glucose‐lipid metabolic index in pancreatic cancer patients with diabetes mellitus

“…The time‐dependent ROC curves demonstrated that TyG (AUC = 0.616), TG/HDL‐c (AUC = 0.674), and TyG‐BMI (AUC = 0.633) all had predictive value for the prognosis of PC patients with diabetes mellitus. Other studies also found IR occurred in 85%–95% of all diabetic patients 30,42 and was associated with the aggressiveness of pancreatic ductal adenocarcinoma 43 . Research has shown that diabetic patients face a higher risk of cancer recurrence and cancer‐related death 11 .…”

“…Diabetes is associated with increased incidence of PC. As economic levels have risen and dietary structures have changed, the prevalence of diabetes mellitus has gradually increased, alongside increased incidence of PC 29,30 . In 50%–80% of PC patients, diabetes mellitus is comorbid, 31,32 and approximately 85% have IGT 33 .…”

“…As economic levels have risen and dietary structures have changed, the prevalence of diabetes mellitus has gradually increased, alongside increased incidence of PC. 29 , 30 In 50%–80% of PC patients, diabetes mellitus is comorbid, 31 , 32 and approximately 85% have IGT. 33 However, several meta‐analyses on the effect of diabetes mellitus on the prognosis of PC have reached contradictory conclusions.…”

“… 43 Research has shown that diabetic patients face a higher risk of cancer recurrence and cancer‐related death. 11 Mechanistically, high insulin levels can promote the proliferation and differentiation of PC cells and angiogenesis through the activation of the insulin and insulin‐like growth factor axis 44 and the PI3K/Akt and MAPK signaling pathways, 30 , 42 leading to PC progression. In addition, IR can induce hyperglycemia, hyperinsulinemia, and dyslipidemia, which may promote PC cells to remodel their metabolic phenotypes and increase their aggressiveness.…”

Primary pancreatic lymphoma: Report of 4 cases with literature review

“…It is the seventh leading cause of cancer death worldwide. The predominant type of PC is pancreatic ductal adenocarcinoma (PDAC), which constitutes over 95% of pancreatic tumors [1] . Other types of exocrine pancreatic cancers include squamous, adenosquamous, colloid carcinoma.…”