Disseminated Well-Differentiated Gastro-Entero-Pancreatic Tumors Are Associated with Metabolic Syndrome

Abstract

The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs (n = 134), classified according to primary tumor location (gastrointestinal or pancreatic), pathological grading (G1 (Ki67 ≤ 2%) and G2 (>3 ≤ 20%) (WHO 2010), disease extension (localized, loco-regional, and metastatic), and presence of hormonal secretion syndrome (functioning/non-functioning), was evaluated for the presence of MetS criteria. After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.

Visceral Obesity Is Associated with Shorter Progression-Free Survival in Well-Differentiated Gastro-Entero-Pancreatic Neuroendocrine Neoplasia

“…Our group has recently described an association between MetS and some MetS individual components, such as visceral obesity and abnormal FPG with WD GEP-NEN [ 17 ]. We have also found that patients with WD GEP-NEN and MetS had a higher risk of presenting a lower tumor grade yet disseminated disease at diagnosis, independently of primary tumor site and hormonal status [ 27 ]. In support of our previous study’s findings, a metanalysis published by Leoncini et.…”

Association between somatostatin analogues and diabetes mellitus in gastroenteropancreatic neuroendocrine tumor patients: A Surveillance, Epidemiology, and End Results‐Medicare analysis of 5235 patients

“…One group has previously observed an association between well‐differentiated GEP‐NETs and metabolic syndrome and visceral obesity. 17 , 18 Higher fasting glucose and glucose intolerance were described previously in two small samples of patients with NETs; however, the prevalence of DM diagnoses in the GEP‐NET population has not been studied. 17 , 25 It has been proposed that DM and neuroendocrine tumors share components in their pathogenesis, though the exact mechanism is not known.…”

“… 17 , 18 Higher fasting glucose and glucose intolerance were described previously in two small samples of patients with NETs; however, the prevalence of DM diagnoses in the GEP‐NET population has not been studied. 17 , 25 It has been proposed that DM and neuroendocrine tumors share components in their pathogenesis, though the exact mechanism is not known. 26 This is supported by studies showing that some medications for diabetes such as metformin have been associated with slower tumor progression in NET patients.…”

“…[14][15][16] Though less common than instances of hyperglycemia, hypoglycemia was observed in 4% of NET patients in the octreotide clinical trials. 11 In NET patients, small studies have suggested an association between GEP-NETs and metabolic syndrome 17 and higher fasting glucose, 18 but these initial studies showed no statistically significant difference in these measures in patients treated with SSAs. Overall, although hyperglycemia is more often suggested than hypoglycemia, the net effect of SSAs on glucose homeostasis in GEP-NET patients is not well-understood.…”

Chronotype: what role in the context of gastroenteropancreatic neuroendocrine tumors?

“…The prevalence and incidence of gastroenteropancreatic neuroendocrine tumors (GEP-NET) is increasing over the past 2 decades, partly due to the growing availability of advanced endoscopic and radiological imaging techniques in detecting more accurately benign and incidentally discovered lesions [ 9 ]. The complex clinical presentation and course of GEP-NET deserves special attention in early diagnosis and treatment, particularly in their association with metabolic consequences that represent risk determinants of well-differentiated GEP-NET, similarly to other types of cancers [ 10 ]. Thus, the management of patients with GEP-NET requires an integrated multidisciplinary approach, and nutrition is an essential component of the assessment and management of these patients [ 11 ].…”