Abstract
The determinants for gastroenteropancreatic neuroendocrine tumors (GEP-NET) recent burden are matters of debate. Obesity and metabolic syndrome (MetS) are well established risks for several cancers even though no link with GEP-NETs was yet established. Our aim in this study was to investigate whether well-differentiated GEP-NETs were associated with obesity and MetS. Patients with well-differentiated GEP-NETs (n = 96) were cross-matched for age, gender, and district of residence with a control group (n = 96) derived from the general population in a case-control study. Patients presented gastro-intestinal (75.0%) or pancreatic (22.9%) tumors, grade G1 (66.7%) or G2 (27.1%) with localized disease (31.3%), regional metastasis (16.7%) or distant metastasis (43.8%) at diagnosis, and 45.8% had clinical hormonal syndromes. MetS was defined according to Joint Interim Statement (JIS) criteria. Well-differentiated GEP-NETs were associated with MetS criteria as well as the individual components’ waist circumference, fasting triglycerides, and fasting plasma glucose (p = 0.003, p = 0.002, p = 0.011 and p < 0.001, respectively). The likelihood of the association was higher when the number of individual MetS components was greater than four. MetS and some individual MetS components including visceral obesity, dyslipidemia, and increased fasting glucose are associated with well-differentiated GEP-NET. This data provides a novel insight in unraveling the mechanisms leading to GEP-NET disease.
Highlights
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are considered a rare entity even though a 6.5-fold increase in incidence was observed in the past four decades [1], which are believed to be predominantly driven by the rising number of the incidental detection of low-stage tumors [2].gastroenteropancreatic neuroendocrine tumors (GEP-NET) are currently the second most frequent digestive tumor only surpassed by colorectal cancer [3]
A large percentage of patients were under blood pressure lowering drugs (50.5%), lipid lowering medications (37.9%), statins (91.7%), and glucose lowering therapy (14.2%) including dipeptidyl peptidase-4 (DPP-4) inhibitors and/or metformin (58.3%), sulfonylureas (16.7%), or insulin
There was no significant difference between WD GEP-NET patients and controls concerning the use of glucose lowering therapy, the proportion of patients under blood pressure (BP) or lipid lowering therapy was significantly higher in patients than in controls (p < 0.001)
Summary
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are considered a rare entity even though a 6.5-fold increase in incidence was observed in the past four decades [1], which are believed to be predominantly driven by the rising number of the incidental detection of low-stage tumors [2].GEP-NETs are currently the second most frequent digestive tumor only surpassed by colorectal cancer [3]. Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are considered a rare entity even though a 6.5-fold increase in incidence was observed in the past four decades [1], which are believed to be predominantly driven by the rising number of the incidental detection of low-stage tumors [2]. Despite the fact that significant advances were made towards the understanding of the genetics and molecular mechanisms associated with NETs, very little is known about the etiology of sporadic tumors or the reasons for the rising incidence observed over the past several decades [5]. Obesity is frequently associated with insulin resistance (IR), which is related to a state of systemic and local low grade chronic inflammatory state responsible for the activation of a number of signaling pathways involving hormone control, cell proliferation, and immunity [6,7] that led to neoplastic transformation of cells
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