Exploring the link between diabetes and pancreatic cancer

Pizzato, Margherita; Turati, Federica; Rosato, Valentina; Vecchia, Carlo La

doi:10.1080/14737140.2019.1642109

Cited by 19 publications

(21 citation statements)

References 88 publications

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“…Based on the biological complexity of PC, a bidirectional relationship between DM and PC has been identified, since 2005 [35]. As stated earlier, many recent studies have concluded that DM is both a consequence, as well as, a cause for PC [36]. Overall, studies report that most patients with pancreatic cancer have hyperglycemia or diabetes.…”

Section: The Pancreas and Insulinmentioning

confidence: 97%

“…The connection between PC and DM has been explained by several translational, clinical and epidemiological studies. The largest original epidemiological studies showed clearly that new-onset hyperglycemia and DM are early signs of PC [28,30,35,36]. As PC is usually diagnosed at the late stage of the disease, given the overall 5 year survival rate is less than 5%, the duration of survival actually depends on the histological TNM grading of tumor and the resection ratio [29,37,38].…”

Section: The Pancreas and Insulinmentioning

confidence: 99%

“…Recent epidemiological studies, and meta-analyses examining the association between the diabetes mellitus and pancreatic cancer indicate that; there is a multidirectional relationship between T2D and PC. Long-standing diabetes is an increased risk factor (1.5 to 2 fold) for PC; and new-onset diabetes (type 3c) is a possible clinical marker of asymptomatic pancreatic cancer [30,35,36,40]. DM, being the most significant disorder of glucose metabolism and as DM is genetically heterogeneous, variants of more than 50 nuclear genes have been found for the genetic risk by genome-wide association studies [16,39].…”

Section: Diabetes Mellitus and Pancreatic Cancer Association At The Cellular Levelmentioning

confidence: 99%

“…To date, several characteristics are identified in genetically engineered mouse models and summarized below for the association of DM and PC. Overall possible mechanisms could be due to mechanical defects, mechanical obstruction and/or enlargement of pancreatic ducts [11,42]; glycogen synthesis defects which are caused by the post-insulin receptor defects and glycogen storage [42]; plasma glucagon levels and islet amyloid polypeptide [39,43]; presence of K-ras codon 12 mutations (p.G12D;p.G12V) [4,13]; prognostic factors as tumor sizes and molecular factors [13]; increased levels of Insulin Growth Factor 1 (IGF-1) and its receptor in promoting carcinogenesis [36,39,44]; activation of Transforming Growth Factor (TGF-β) signaling and depletion of β-cells in Langerhans islets [45,46]; hyperglycemia induced levels of hydrogen peroxide that up regulates manganese superoxide dismutase (SOD2) expression that activates ERK and p38MAPK pathways, NF-kP and AP-1 transcription factors [25,47] and hyperglycemia induced levels of glycation end products that increases inflammation and metastatic ability, increased cytokines and receptors like epidermal growth factor (EGF), epidermal growth factor receptor (EGFR), Glial cell line derived neutrophilic factor (GDNF) [36,46,48] are potentially involved mechanisms in the pathobiology of pancreatic cancer [13,15,38,46,[49][50][51].…”

Section: Diabetes Mellitus and Pancreatic Cancer Association At The Cellular Levelmentioning

confidence: 99%

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Review of Diabetes Mellitus in Relation to Pancreatic Cancer

2021

Clinical Medical Case Reports and Reviews

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Background Global Epidemiology of Pancreatic CancerToday's statistical studies implicate that PC is the fourth leading cause of death among all the cancers, and is even projected to become the second leading cause of death in the coming years [1]. For this highly aggressive and devastating malignancy it is known that pancreatic cancer's incidence and mortality patterns differ among populations. Overall clinical data show 93% pancreatic cancers are exocrine adenocarcinoma with the remainder (7%) being pancreatic neuroendocrine tumors. Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal with a 5-year survival rate of 8.2% in United States and Europe [1,2] (American Cancer Society; https://www. cancer.org). ASCO guidelines for the management of locally advanced pancreatic (LAPC) with an expected 5-year overall survival rate of less than 5% are more limited than for a potentially curable disease, and much more so for metastatic pancreatic cancer whose patients have less than 1-year median life expectancy with the 5-year overall survival rate of only 2% [3].It is estimated that during 2020 in the United States, 57,600 adults (30,400 men and 27,200 women) will be diagnosed with PC, 3-7% of all cancers in the US population [4]. Whereas Europe and the European Union (40 total countries) comprise 9% of the world population, the region has a 25% share of the global cancer (burden) and thus provides key cancer planning programs (European Network of Cancer Registries, ENCR, www.encr.eu and United Nations, population division, World Population Prospects, https://esa.un.org/ unpd/wpp/). In 2018, estimated incidence of new PC cases and

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Section: The Pancreas and Insulinmentioning

confidence: 97%

Section: The Pancreas and Insulinmentioning

confidence: 99%

Section: Diabetes Mellitus and Pancreatic Cancer Association At The Cellular Levelmentioning

confidence: 99%

Section: Diabetes Mellitus and Pancreatic Cancer Association At The Cellular Levelmentioning

confidence: 99%

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Review of Diabetes Mellitus in Relation to Pancreatic Cancer

2021

Clinical Medical Case Reports and Reviews

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“…Obesity and high caloric intake linked co-morbidities like type 2 diabetes (T2D) have been attributed as being risk factors for a number of cancers including pancreatic cancer [1,2]. Apart from being considered as one of the risk factors for pancreatic cancer, late onset of diabetes is now being evaluated as a potential early biomarker for pancreatic cancer [3][4][5]. Studies have shown that pancreatic cancer patients with T2D have poor survival statistics [6].…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes induced microbiome dysbiosis is associated with therapy resistance in pancreatic adenocarcinoma

et al. 2020

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Resistance to therapy is one of the major factors that contribute to dismal survival statistics in pancreatic cancer. While there are many tumor intrinsic and tumor microenvironment driven factors that contribute to therapy resistance, whether pre-existing metabolic diseases like type 2 diabetes (T2D) contribute to this has remained understudied. It is well accepted that hyperglycemia associated with type 2 diabetes changes the gut microbiome. Further, hyperglycemia also enriches for a "stem-like" population within the tumor. In the current study, we observed that in a T2D mouse model, the microbiome changed significantly as the hyperglycemia developed in these animals. Our results further showed that, tumors implanted in the T2D mice responded poorly to gemcitabine/paclitaxel (Gem/Pac) standard of care compared to those in the control group. A metabolomic reconstruction of the WGS of the gut microbiota further revealed that an enrichment of bacterial population involved in drug metabolism in the T2D group. Additionally, we also observed an increase in the CD133+ tumor cells population in the T2D model. These observations indicated that in an animal model for T2D, microbial dysbiosis is associated with increased resistance to chemotherapeutic compounds.© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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

Wang,

Ruan,

et al. 2024

Cancer Medicine

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BackgroundThe incidence of pancreatic cancer (PC) is higher in diabetic patients due to disturbances in glucose and lipid metabolism caused by insulin resistance (IR). However, the effect of diabetes as well as IR on the prognosis of PC patients remains inconclusive. Our study aims to assess the impact of IR on the prognosis of PC patients with diabetes.MethodsWe conducted a retrospective analysis of 172 PC patients with diabetes in our institute from 2015 to 2021. Prognostic assessment was performed using univariate/multifactorial analysis and survival analysis. The predictive efficacy of metabolic indices was compared using receiver operator characteristic (ROC) curve analysis.ResultsOne hundred twenty‐one of 172 patients died during follow‐up, with a median follow‐up of 477 days and a median overall survival (OS) of 270 days. Survival analysis showed a significant difference in OS by IR related parameters, which were triglyceride‐glucose index (TyG), triglyceride‐glucose index‐body mass index (TyG‐BMI), and triglyceride/high‐density lipoprotein cholesterol ratio (TG/HDL‐c). The ROC curve indicated that TyG, TyG‐BMI, and TG/HDL‐c had prognostic efficacy for PC with diabetes. We next optimized TyG‐BMI and obtained a new parameter, namely glucose‐lipid metabolism index (GLMI), and the patients were classified into GLMI low group and high group based on the calculated cutoff value. The GLMI high group had higher TyG, TyG‐BMI, TyG/HDL‐c, BMI, TG, total cholesterol (TC), TC/HDL‐c, fasting plasma glucose, CA199, and more advanced tumor stage compared to low group. Univariate and multivariate analyses showed that GLMI was an independent prognostic factor. Furthermore, the patients of GLMI high group had worse OS compared to low group and the ROC curves showed GLMI had better predictive ability than TyG and TyG‐BMI.ConclusionsIR is associated with the outcome of PC patients with diabetes and higher level of IR indicates worse prognosis. GLMI has a good predictive value for PC with diabetes.

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Exploring the link between diabetes and pancreatic cancer

Cited by 19 publications

References 88 publications

Review of Diabetes Mellitus in Relation to Pancreatic Cancer

Review of Diabetes Mellitus in Relation to Pancreatic Cancer

Type 2 diabetes induced microbiome dysbiosis is associated with therapy resistance in pancreatic adenocarcinoma

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

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