Letter to the Editor Regarding Prospective Assessment for Prediabetes and New-Onset Diabetes in High-Risk Individuals Undergoing Pancreatic Cancer Screening

Abstract

We read with great interest the study by Shah et al1Shah I. et al.Gastroenterology. 2021; 161: 1689-1691Abstract Full Text Full Text PDF PubMed Scopus (9) Google Scholar entitled “Prospective Assessment for Prediabetes and New-Onset Diabetes in High-Risk Individuals Undergoing Pancreatic Cancer Screening.” The investigators researched the incidence of prediabetes and diabetes mellitus in high-risk individuals undergoing pancreatic cancer screening. In this study, the authors included high-risk individuals with known genetic mutations or other risk factors who were undergoing screening endoscopic ultrasound. However, we would like to elaborate on the association between prediabetes and the risk for developing pancreatic ductal adenocarcinoma (PDAC) in the general population. The pancreatic cancer cells have a higher requirement of glucose (“glucose addiction”) and the associated hyperglycemia is due to insulin resistance, loss of glucose homeostasis due to pro-inflammatory alterations, and perturbations in beta cell functions.2Korc M. Pancreas. 2019; 48: 594-597Crossref PubMed Scopus (5) Google Scholar⁠ Hyperglycemia and hyperinsulinemia can increase tumor burden and is already present during the stages of prediabetes, thus suggesting that prediabetes could also increase the risk of developing PDAC.3Liao W.C. et al.BMJ. 2015; 349: 1-11Crossref Scopus (2) Google Scholar⁠ Liao et al3Liao W.C. et al.BMJ. 2015; 349: 1-11Crossref Scopus (2) Google Scholar reported that every 0.56 mmol/L increase in fasting blood glucose (FBG) is associated with a 14% increase in the risk of developing PDAC.⁠ Koo et al4Koo D.H. et al.J Clin Endocrinol Metab. 2019; 104: 4594-4599Crossref PubMed Scopus (19) Google Scholar also showed that the incidence of PDAC significantly increases with increasing FBG levels even in prediabetes range.⁠ Both studies showed a linear relationship between FBG and PDAC in prediabetes after adjusting for known risk factors. This is possibly explained by the fact that pancreatic cancer cells require glucose for growth.3Liao W.C. et al.BMJ. 2015; 349: 1-11Crossref Scopus (2) Google Scholar⁠ It is also known that after resection of pancreatic cancer, the diabetes mellitus resolved in 57% of the patients with PDAC.5Sharma A. et al.Gastroenterology. 2018; 155: 490-500.e2Abstract Full Text Full Text PDF PubMed Scopus (94) Google Scholar⁠ Boursi et al6Boursi B. et al.Eur J Gastroenterol Hepatol. 2022; 34: 33-38Crossref PubMed Scopus (11) Google Scholar were able to develop an unvalidated clinical prediction model to assess risk for PDAC among patients with prediabetes. They retrospectively included patients from the general UK population with impaired FBG who developed PDAC within 3 years of the initial diagnosis. The final model included age, body mass index, proton pump inhibitor use, and other biochemical laboratory values and achieved good discrimination (area under the curve, 0.71 [95% confidence interval, 0.67–0.75]). Because there is a clear association between high blood glucose levels and PDAC, we need to ask whether prediabetes is an independent risk factor for the development of PDAC in the general population, if so, we need better predictive models to assess the risk of developing PDAC and institute early management strategies to reverse the prediabetic state. Prospective Assessment for Prediabetes and New-Onset Diabetes in High-Risk Individuals Undergoing Pancreatic Cancer ScreeningGastroenterologyVol. 161Issue 5PreviewPancreatic cancer screening guidelines recommend that individuals at high risk for pancreatic cancer be screened for new-onset diabetes annually, in addition to undergoing screening with endoscopic ultrasound (EUS) and Magnetic Resonance Imaging.1 Although studies have found that new-onset diabetes may be an early sign of pancreatic cancer, incorporating this parameter into a screening program has not been reported.2 The aim of our study was to determine the incidence of prediabetes and diabetes in high-risk individuals undergoing pancreatic cancer screening. Full-Text PDF ReplyGastroenterologyVol. 162Issue 6PreviewThe association between type 2 diabetes and pancreatic cancer has been well established. A large meta-analysis that included mostly patients with type 2 diabetes showed that patients with diabetes were almost twice as likely to develop pancreatic cancer compared with those without diabetes.1 Patients with diabetes have also been shown to have larger tumor size and higher rates of nodal and perineural invasion.2 Full-Text PDF