Diabetes Mellitus in the Middle-Aged and Elderly Population (>45 Years) and Its Association With Pancreatic Cancer: An Updated Review

Abstract

Diabetes mellitus (DM) and pancreatic cancer (PC) in the elderly are widely considered to be interrelated. New-onset diabetes (NOD) patients are considered a high-risk group for the development of PC within three years of diagnosis. We reviewed the literature to determine the pathophysiological association between DM and PC, which can help in the development of screening tests for early PC diagnosis in the elderly with NOD. We also studied the potential associations between them after pancreaticoduodenectomy (PD) or pancreatic resection. We collected studies published in the last five years in PubMed that are relevant to DM and PC in the elderly. We mainly focused on the pathophysiology and intracellular mechanisms involved between NOD and PC. We illustrated the clinical signs and immunological and metabolic biomarkers that can be used to diagnose early PC in the elderly with NOD. In the 34 studies we reviewed, five showed that long-term diabetes mellitus (LTDM) increases the risk of PC. Six studies showed that NOD in the elderly is an early sign of PC. Fourteen studies proposed that clinical signs and biomarker levels should be used to determine the high-risk risk group for PC among NOD patients. Six studies reported that NOD is associated with the worst outcomes postoperatively, and three studies showed that patients developed DM after pancreatic resection. LTDM is considered an independent risk factor for PC development in the elderly. NOD is a consequence and maybe the only early presenting sign of PC. Screening protocols and tests should be used in clinical practice to determine the proportion of NOD patients who should undergo further testing for early diagnosis of PC. DM and PC are also co-related postoperatively and patients should be monitored for impaired glucose levels, overall survival, and mortality.

Nutrition in Cancer Therapy in the Elderly—An Epigenetic Connection?

“…In the context of this review, the most important result of this study was that death was more often due to non-cancer causes, which supports the complexity of considerations surrounding the care of older adults with cancer. On the other hand, it is not easy to assess the real role of cancer in deaths whose immediate reason was T2DM, as cancer and T2DM have much in common and affect each other [16].…”

Pancreatic cancer among solid organ transplant recipients in the United States

“…Blood type O has been identi ed as a protective factor for PC, although the mechanism is unknown. Diabetes mellitus is associated with development of PC in the general population 30 with a pooled relative risk of 2.1 reported in a 1995 meta-analysis. 31 Diabetes at the time of transplantation was present in 28% of our cohort (data not shown).…”

Could Microbiome Be the Common Co-Denominator between Type 2 Diabetes and Pancreatic Cancer?

“…Despite the significant prevalence of both diseases, the data elucidating such a complex and bidirectional relationship are relatively scarce. For example, due to insulin resistance, an increase in insulin signaling pathways and insulin-like growth factor-1 (IGF-1) levels in T2DM can also lead to the proliferation and inhibition of apoptosis in PC, as IGF-1 receptors are usually highly expressed in PC cells [14,15]. Furthermore, T2DM is characterized by hyperglycemia, which does not increase neoplastic growth but can trigger oxidative stress, a factor in cancer pathogenesis.…”

“…Additionally, several tumor-secreting products and metabolites such as amino acids, bile acids, and sphingolipids have been shown to be increased in PC after new-onset T2DM and could all play a role in PC development. On the other hand, developing paraneoplastic syndromes in PC can lead to insulin resistance [14].…”