Abstract
BackgroundObesity, mainly visceral obesity, and metabolic syndrome (MetS) are major risk factors for the development of type 2 diabetes, cardiovascular diseases, and cancer. Data analyzing the association of obesity and MetS with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are lacking. Fatty liver index (FLI) is a non-invasive tool for identifying individuals with non-alcoholic fatty liver disease (NAFLD). Visceral adiposity index (VAI) has been suggested as a gender-specific indicator of adipose dysfunction. Both indexes have been proposed as early predictors of MetS. This study aimed to investigate the association of FLI VAI as early predictors of MetS with gastroenteropancreatic neuroendocrine tumors (GEP-NETs).MethodsA cross-sectional, case–control, observational study was carried out at the ENETS Centers of Excellence Multidisciplinary Group for Neuroendocrine Tumors, University “Federico II”. VAI and FLI were calculated.ResultsWe enrolled 109 patients with histologically confirmed G1/G2 GEP-NET (53 M; 57.06 ± 15.96 years), as well as 109 healthy subjects, age, sex- and body mass index-matched. Forty-four GEP-NET patients were G2, of which 21 were with progressive disease, and 27 patients had metastases. GEP-NET patients had a higher value of VAI (p < 0.001) and FLI (p = 0.049) and higher MetS presence (p < 0.001) compared with controls. VAI and FLI values and MetS presence were higher in G2 than in G1 patients (p < 0.001), in patients with progressive disease, and in metastatic vs non-metastatic patients (p < 0.001). In addition, higher values of VAI and FLI and higher MetS presence were significantly correlated with the worst clinical severity of NENs. The cut-off values for the FLI and MetS to predict high grading of GEP-NETs and the presence of metastasis were also provided.ConclusionsThis is the first study investigating an association between VAI and FLI as early predictors of MetS and GEP-NET. Our findings report that the worsening of clinicopathological characteristics in GEP-NET is associated with higher presence of MetS, NAFLD, evaluated by FLI, and visceral adiposity dysfunction, evaluated by VAI. Addressing the clinical evaluation of MetS presence, NAFLD, and visceral adiposity dysfunction might be of crucial relevance to establish targeted preventive and treatment interventions of NEN-related metabolic comorbidities.
Highlights
Neuroendocrine neoplasms (NENs) represent a group of tumors characterized by a wide biological variability and clinical heterogeneity
Even when we considered the difference of Visceral adiposity index (VAI), Fatty liver index (FLI), and metabolic syndrome (MetS) according to specific cut-off points, GEP-Neuroendocrine tumors (NET) patients with progressive disease had the highest percentage of cardiometabolic indices, single risk factors of MetS and presence of MetS (p = 0.014) compared to GEP-NET patients free of the disease or with stable disease, Figure 3
A MetS >1 (p < 0.001, sensitivity 81.5%, specificity 52.4%, area under the curve (AUC) 0.72, standard error 0.059; Figure 5C) and a FLI >61.2 (p = 0.001, sensitivity 74.1%, specificity 70.3%, AUC 0.72, standard error 0.058; Figure 5D) could serve as a threshold for significantly increased risk of presence of metastasis. In this cross-sectional, case–control, observational study, we evaluated the associations of VAI and FLI, as cardiometabolic indices, and MetS with tumor clinicopathological characteristics in a selected group of GEP-NET patients
Summary
Neuroendocrine neoplasms (NENs) represent a group of tumors characterized by a wide biological variability and clinical heterogeneity. When NENs are not associated with any endocrine syndrome, their diagnosis may be delayed for years by non-specificity of presenting, with the frequent progression to a metastatic stage prior to clinical diagnosis [3,4,5]. Data analyzing the association of obesity and MetS with gastroenteropancreatic neuroendocrine neoplasms (GEP-NEN) are lacking. Visceral adiposity index (VAI) has been suggested as a gender-specific indicator of adipose dysfunction. Both indexes have been proposed as early predictors of MetS. This study aimed to investigate the association of FLI VAI as early predictors of MetS with gastroenteropancreatic neuroendocrine tumors (GEP-NETs)
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