Publications by authors named "Silvia Savastano"

166 Publications

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

J Transl Med 2021 07 30;19(1):324. Epub 2021 Jul 30.

Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples, Via Sergio Pansini 5, 80131, Naples, Italy.

Background: Chronotype is defined as a trait determining the subject circadian preference in behavioral and biological rhythms relative to external light-dark cycle. Although individual differences in chronotype have been associated with an increased risk of developing some types of cancer, no studies have been carried out in gastroenteropancreatic neuroendocrine tumors (GEP-NET).

Materials: We investigate the differences in chronotype between 109 GEP-NET and 109 healthy subjects, gender-, age-, and BMI-matched; and its correlation with tumor aggressiveness.

Results: GEP-NET patients have a lower chronotype score (p = 0.035) and a higher percentage of evening chronotype (p = 0.003) than controls. GEP-NET patients with morning chronotype had lower BMI, waist circumference, and higher percentage of MetS (p < 0.001) than evening type. Interestingly, considering the clinical pathological characteristics, patients with the presence of metastasis, grading G2, and in progressive disease presented the lower chronotype score (p = 0.004, p < 0.001, and p = 0.002; respectively) compared to other categories. Chronotype score was negatively associated with anthropometric measurements, metabolic profile, percentage of MetS, and Ki67 index (p < 0.001 for all).

Conclusions: GEP-NET patients have an unhealthy metabolic profile and present more commonly an evening chronotype. These results support the importance of including the assessment of chronotype in an adjunctive tool for the prevention of metabolic alterations and tumor aggressiveness of GEP-NET.
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http://dx.doi.org/10.1186/s12967-021-03010-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325322PMC
July 2021

Association of Trimethylamine N-Oxide (TMAO) with the Clinical Severity of Hidradenitis Suppurativa (Acne Inversa).

Nutrients 2021 Jun 10;13(6). Epub 2021 Jun 10.

Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O.), Endocrinology Unit, Department of Clinical Medicine and Surgery, University Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.

In this case-control, cross-sectional, observational study, we evaluated circulating trimethylamine n-oxide (TMAO) levels, a gut-derived metabolite associated with inflammation and cardiometabolic risk, in patients with hidradenitis suppurativa (HS), a highly disabling inflammatory skin disease associated with an elevated prevalence of comorbidities, especially cardiovascular and metabolic diseases. In this study, we enrolled 35 naive-treatment patients with HS and 35 controls, matched for sex, age, and body mass index (BMI). HS Sartorius score was 49.0 (33.0-75.0), while according to the Harley system 12 and 23 patients presented grade 1 and grade 2 severity, respectively. HS patients had a lower adherence to the Mediterranean diet (MD) ( = 0.002), lower phase angle (PhA) ( < 0.001), and higher circulating TMAO levels ( < 0.001) than the control group. HS patients with grade 2 rather than grade 1 of Harley grade severity showed a higher BMI ( = 0.007), waist circumference ( = 0.016), total energy intake ( = 0.005), and lower PhA ( < 0.001) and adherence to the MD ( = 0.003). Of interest, patients with Hurley grade 2 of severity exhibited higher circulating TMAO levels ( < 0.001) compared to grade 1. Circulating TMAO levels showed a positive correlation with HS Sartorius score even after adjustment for confounding covariates, including BMI, waist circumference, adherence to the MD, total energy intake, and PhA (r = 0.570, = 0.001). Using a linear regression model, circulating TMAO levels and PhA were the main predictors of the clinical severity of HS.
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http://dx.doi.org/10.3390/nu13061997DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8226830PMC
June 2021

Obesity-related gut hormones and cancer: novel insight into the pathophysiology.

Int J Obes (Lond) 2021 Jun 4. Epub 2021 Jun 4.

Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università Federico II di Napoli, Naples, Italy.

The number of cancers attributed to obesity is increasing over time. The mechanisms classically implicated in cancer pathogenesis and progression in patients with obesity involve adiposity-related alteration of insulin, sex hormones, and adipokine pathways. However, they do not fully capture the complexity of the association between obesity-related nutritional imbalance and cancer. Gut hormones are secreted by enteroendocrine cells along the gastrointestinal tract in response to nutritional cues, and act as nutrient sensors, regulating eating behavior and energy homeostasis and playing a role in immune-modulation. The dysregulation of gastrointestinal hormone physiology has been implicated in obesity pathogenesis. For their peculiar function, at the cross-road between nutrients intake, energy homeostasis and inflammation, gut hormones might represent an important but still underestimated mechanism underling the obesity-related high incidence of cancer. In addition, cancer research has revealed the widespread expression of gut hormone receptors in neoplastic tissues, underscoring their implication in cell proliferation, migration, and invasion processes that characterize tumor growth and aggressiveness. In this review, we hypothesize that obesity-related alterations in gut hormones might be implicated in cancer pathogenesis, and provide evidence of the pathways potentially involved.
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http://dx.doi.org/10.1038/s41366-021-00865-8DOI Listing
June 2021

Association of the Chronotype Score with Circulating Trimethylamine N-Oxide (TMAO) Concentrations.

Nutrients 2021 May 14;13(5). Epub 2021 May 14.

Centro Italiano per la cura e il Benessere del Paziente con Obesità (C.I.B.O), Endocrinology Unit, Department of Clinical Medicine and Surgery, University Federico II, 80131 Naples, Italy.

Individual differences in the chronotype, an attitude that best expresses the individual circadian preference in behavioral and biological rhythms, have been associated with cardiometabolic risk and gut dysbiosis. Up to now, there are no studies evaluating the association between chronotypes and circulating TMAO concentrations, a predictor of cardiometabolic risk and a useful marker of gut dysbiosis. In this study population (147 females and 100 males), subjects with the morning chronotype had the lowest BMI and waist circumference ( < 0.001), and a better metabolic profile compared to the other chronotypes. In addition, the morning chronotype had the highest adherence to the Mediterranean diet ( < 0.001) and the lowest circulating TMAO concentrations ( < 0.001). After adjusting for BMI and adherence to the Mediterranean diet, the correlation between circulating TMAO concentrations and chronotype score was still kept (r = -0.627, < 0.001). Using a linear regression analysis, higher chronotype scores were mostly associated with lower circulating TMAO concentrations (β = -0.479, = -12.08, and < 0.001). Using a restricted cubic spline analysis, we found that a chronotype score ≥59 ( < 0.001, R = -0.824) demonstrated a more significant inverse linear relationship with circulating TMAO concentrations compared with knots <59 (neither chronotype) and <41 (evening chronotype). The current study reported the first evidence that higher circulating TMAO concentrations were associated with the evening chronotype that, in turn, is usually linked to an unhealthy lifestyle mostly characterized by low adherence to the MD.
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http://dx.doi.org/10.3390/nu13051671DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8156852PMC
May 2021

Morbid Obesity and Thyroid Cancer Rate. A Review of Literature.

J Clin Med 2021 Apr 27;10(9). Epub 2021 Apr 27.

Department of Advanced Biomedical Sciences, University of Naples "Federico II", Via Pansini n. 5, 80131 Naples, Italy.

In the past three decades, several recent studies have analyzed the alarming increase of obesity worldwide, and it has been well established that the risk of many types of malignancies is increased in obese individuals; in the same period, thyroid cancer has become the fastest growing cancer of all malignancies. We investigated the current literature to underline the presence of a connection between excess body weight or Body Mass Index (BMI) and risk of thyroid cancer. Previous studies stated that the contraposition between adipocytes and adipose-resident immune cells enhances immune cell production of multiple pro-inflammatory factors with subsequent induction of hyperlipidemia and vascular injury; these factors are all associated with oxidative stress and cancer development and/or progression. Moreover, recent studies made clear the mitogenic and tumorigenic action of insulin, carried out through the stimulation of mitogen-activated protein kinase (MAPK) and phosphoinositide-3 kinase/AKT (PI3K/AKT) pathways, which is correlated to the hyperinsulinemia and hyperglycemia found in obese population. Our findings suggest that obesity and excess body weight are related to an increased risk of thyroid cancer and that the mechanisms that combine overweight with this cancer should be searched for in the adipokine pathways and chronic inflammation onset.
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http://dx.doi.org/10.3390/jcm10091894DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8123763PMC
April 2021

Phase Angle as an Easy Diagnostic Tool of Meta-Inflammation for the Nutritionist.

Nutrients 2021 Apr 24;13(5). Epub 2021 Apr 24.

Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), Endocrinology Unit, Department of Clinical Medicine and Surgery, University Medical School of Naples, Via Sergio Pansini 5, 80131 Naples, Italy.

Phase angle (PhA), a noninvasive bioimpedance marker, is a useful tool for nutritional screening in several diseases. C-reactive protein (CRP), a strong risk factor for metabolic and cardiovascular diseases, is a commonly used biomarker of meta-inflammation. As both PhA and CRP are influenced by age, BMI, and nutritional status, and exhibit a clear sex dimorphism, we examined the association between PhA and CRP levels in 1855 subjects (680 males and 1175 females), aged 18-59 years, with BMIs ranging from 19.5 to 69.4 kg/m, stratified according to sex. PhA values and CRP levels were significantly lower in females than males ( < 0.001), while the adherence to the Mediterranean diet (MD) was lower in males compared to females ( < 0.001). After adjusting for age, physical activity, BMI, waist circumference, and adherence to the MD, PhA remained negatively associated with CRP levels in both genders ( < 0.001). In the ROC analysis, PhA ≤ 5.5° in males and ≤5.4° in females were the threshold values predicting increased hs-CRP levels. These results suggested that PhA might represent a valid predictor of CRP levels in both sexes regardless of body weight and adherence to the MD, which avoids the collection of blood sampling and expensive biochemical assays.
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http://dx.doi.org/10.3390/nu13051446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8145306PMC
April 2021

The clock diet: a practical nutritional guide to manage obesity through chrononutrition.

Minerva Med 2021 Apr 29. Epub 2021 Apr 29.

Endocrinology Unit, Department of Clinical Medicine and Surgery, Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), University Medical School of Naples, Naples, Italy.

Chronobiology studies the biological rhythms or circadian cycles of living organisms and their adaptation to external changes. Biological rhythms can affect hormone production cycles such as sleep/wake, and nutrition/fasting, but these factors can also alter the circadian rhythm (CR). In recent years, numerous studies have highlighted how feeding times and frequency can influence biological rhythms. Additionally, individuals' chronotype, working shifts, and food intake can make a deep impact on people's tendency to develop obesity and metabolic diseases. In this context, a single food and a specific combination of these, can also affect the CR and fasting cycle and consequently body weight and viceversa. The purpose of the review is to propose practical nutritional recommendations to help in resynchronizing the circadian rhythm as a tool in weight control.
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http://dx.doi.org/10.23736/S0026-4806.21.07207-4DOI Listing
April 2021

Phase angle and Mediterranean diet in patients with acne: Two easy tools for assessing the clinical severity of disease.

J Transl Med 2021 04 26;19(1):171. Epub 2021 Apr 26.

Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Background: Acne is a chronic, inflammatory and debilitating skin disorder. Dietary factors and nutritional status are among the exacerbating factors of acne. Phase angle (PhA), a direct measure of Bioelectrical Impedance Analysis (BIA), represents an indicator of the chronic inflammatory state. The Mediterranean diet (MD) is a healthy dietary pattern that can exert anti-inflammatory effects in several inflammatory diseases. We aimed to investigate the difference in PhA and adherence to the MD and their associations with the severity of acne in a sample of naïve treatment patients with acne compared to control group.

Materials: In this cross-sectional, case-control, observational study, we enrolled 51 patients with acne and 51 control individuals. Body composition was evaluated by a BIA phase-sensitive system (50 kHz BIA 101 RJL, Akern Bioresearch, Florence, Italy, Akern). For adherence to the MD, we have used the PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. The clinical severity of acne was assessed by using the global acne grading system (GAGS), a quantitative scoring system to assess acne severity.

Results: Patients with acne had a worse body composition, in particular smaller PhA (p = 0.003), and a lower adherence to the MD (p < 0.001) than the control group, in spite of no differences in gender, age and BMI between the two groups. Stratifying patients with acne according to GAGS categories, both PhA (p = 0.006) and PREDIMED score (p = 0.007) decreased significantly in severe acne than mild/moderate acne. The GAGS score was negative correlations with PhA (r = - 0.478, p < 0.001) and PREDIMED score (r = - 0.504, p < 0.001). The results of the multivariate analysis showed PhA and PREDIMED score were the major determinants of GAGS score (p < 0.001). The receiver operator characteristic (ROC) analysis reporting a value of PhA of ≤ 6.1° and a PREDIMED score of ≤ 9 identified patients with acne with the highest clinical severity of the disease.

Conclusions: Novel correlations were reported between PhA and the degree of adherence to the MD with acne severity. Of interest, PhA and PREDIMED scores might represent possible markers of the severity of acne in a clinical setting. This study highlights how a cooperation between dermatologist and nutritionists might provide a combination key in the complex management of acne patients.
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http://dx.doi.org/10.1186/s12967-021-02826-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8074493PMC
April 2021

Diet as a possible influencing factor in thyroid cancer incidence: the point of view of the nutritionist.

Panminerva Med 2021 04 20. Epub 2021 Apr 20.

Endocrinology Unit, Department of Clinical Medicine and Surgery, Centro Italiano per la Cura e il Benessere del Paziente con Obesità (C.I.B.O), University Medical School of Naples, Naples, Italy.

The incidence of differentiated thyroid cancer has increased in the last decades all over the world. Different environmental factors are possible perpetrators of this exponential growth. Nutritional factors are among the main environmental factors studied for thyroid cancer in recent years. This review aims to overview the main dietary factors involved in thyroid cancer risk, providing specific nutrition recommendations from the endocrinological Nutritionist point of view. Among the single food, fish and shellfish are the primary natural source of iodine, selenium and vitamin D in the human diet. These nutrients are essential for the synthesis of thyroid hormones; however, their consumption is not consistently related to thyroid cancer risk. The high intake of fruit and vegetables, probably due to their vitamin and antioxidant content, shows a weak inverse association with thyroid cancer risk. Alcohol, meat, or other food groups/nutrients showed no significant effect on thyroid cancer. In conclusion, to date, no definite association among dietary factors, specific dietary patterns, and thyroid cancer, and its clinical severity and aggressiveness have been found. However, it is essential to underline that in the future, prospective studies should be carried out to precisely evaluate the qualitative and quantitative intake of nutrients by patients to establish with more confidence a potential correlation between food intake and the occurrence and development of thyroid cancer.
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http://dx.doi.org/10.23736/S0031-0808.21.04213-0DOI Listing
April 2021

Cut-off for the Mediterranean diet score to identify subjects with morning chronotype in middle-aged Italian adults.

Minerva Endocrinol (Torino) 2021 Apr 15. Epub 2021 Apr 15.

Unit of Endocrinology, Dipartimento di Medicina Clinica e Chirurgia, Federico II University Medical School of Naples, Naples, Italy.

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http://dx.doi.org/10.23736/S2724-6507.21.03411-8DOI Listing
April 2021

What about Mediterranean diet as tool to improve sleep quality in obesity?

Minerva Endocrinol (Torino) 2021 Apr 15. Epub 2021 Apr 15.

Unit of Endocrinology, Dipartimento di Medicina Clinica e Chirurgia, Federico II University Medical School of Naples, Naples, Italy.

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http://dx.doi.org/10.23736/S2724-6507.21.03410-6DOI Listing
April 2021

Cardio-Metabolic Indices and Metabolic Syndrome as Predictors of Clinical Severity of Gastroenteropancreatic Neuroendocrine Tumors.

Front Endocrinol (Lausanne) 2021 18;12:649496. Epub 2021 Mar 18.

Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Endocrinology Unit, Department of Clinical Medicine and Surgery, University Medical School of Naples, Naples, Italy.

Background: Obesity, 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).

Methods: A 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.

Results: We 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 ( < 0.001) and FLI ( = 0.049) and higher MetS presence ( < 0.001) compared with controls. VAI and FLI values and MetS presence were higher in G2 than in G1 patients ( < 0.001), in patients with progressive disease, and in metastatic non-metastatic patients ( < 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.

Conclusions: This 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.
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http://dx.doi.org/10.3389/fendo.2021.649496DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8018238PMC
March 2021

Nutritional guidelines for the management of insulin resistance.

Crit Rev Food Sci Nutr 2021 Apr 2:1-14. Epub 2021 Apr 2.

Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università "Federico II" di Napoli, Via Sergio Pansini, 5, Naples, Italy.

Obesity and its related co-morbidities, namely type 2 diabetes (T2D), pose a significant global public health problem. Insulin resistance (IR) in muscle and liver is the core pathophysiologic defect that underlies obesity preceding and predicting the onset of T2D in susceptible humans. There is a broad population with IR that has no indication for prescription of medications, who still need medical consultation and specific advice in this respect. This prevalent need can be achieved by appropriate diet, exercise, and other behavioral therapies for lifestyle interventions. Despite a well-recognized role of IR in the progression to metabolic diseases, no specific nutritional recommendations exist to manage this condition, to the best of our knowledge. An international panel of experts reviewed and critically appraised the updated literature published about this topic. This review primarily examines the evidence for areas of consensus and ongoing uncertainty or controversy about diet and exercise approaches for IR. The aim of this article is to present the most common IR states, namely obesity and Polycystic Ovary Syndrome (PCOS), and provide nutritional advice to manage IR, hyperinsulinemia, and reactive hypoglycemia. These nutritional guidelines could prevent progression or worsening of IR with resultant beta-cell failure and, as a result, T2D.
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http://dx.doi.org/10.1080/10408398.2021.1908223DOI Listing
April 2021

Chronotype and cardio metabolic health in obesity: does nutrition matter?

Int J Food Sci Nutr 2021 Mar 24:1-9. Epub 2021 Mar 24.

Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università "Federico II" di Napoli, Naples, Italy.

The aim of the study was to investigate the association of chronotype categories with type 2 diabetes mellitus (T2DM) and cardiovascular diseases (CVD) in 172 middle-aged adults (71.5% females; 51.8 ± 15.7 years). Anthropometric parameters, lifestyle habits, adherence to the Mediterranean Diet (MD), sleep quality, chronotype and the presence of T2DM and CVD were studied. Chronotype was classified as morning in 58.1% of subjects, evening in 12.8% and intermediate in 28.1%. Subjects with evening chronotype followed an unhealthier lifestyle than other chronotypes; indeed, they significantly performed less regular activity and were more frequently smokers. Furthermore, they had significantly higher risk to have T2DM [Odds Ratio (OR)=3.36 95% confidence interval (CI) 1.14-35.42;  = 0.03] and CVD [Odds Ratio (OR)= 5.89 95% CI 1.14-30.60;  = 0.035](CI) 2.24-407.54);  = 0.01] compared to morning chronotype after adjustment for gender, body mass index (BMI), sleep quality and adherence to the MD. The confidence intervals were wide, indicating that the sample size was too small. Thus, these data need to be replicated in a larger sample size. In addition, nutritional assessment was limited since only PREDIMED questionnaire was carried out. However, the main strengths of this study included a random sample and a population-based approach, although the cross-sectional design cannot establish causality. Although study population was unbalanced per gender and smoking and age group representing only middle-aged people,we adjusted the statistical analysis for potential confounding factors. In conclusion, the evening chronotype has an increased risk to be associated to T2DM and CVD.
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http://dx.doi.org/10.1080/09637486.2021.1885017DOI Listing
March 2021

The impact of obesity on immune response to infection: Plausible mechanisms and outcomes.

Obes Rev 2021 06 14;22(6):e13216. Epub 2021 Mar 14.

Dipartimento di Medicina Clinica e Chirurgia, Unità di Endocrinologia, Università Federico II di Napoli, Napoli, Italy.

Emerging data suggest an association between obesity and infectious diseases. Although the mechanisms underlying this link are not well established, a number of potential factors may be involved. Indeed, the obesity-related vulnerability to infectious diseases could be due to chronic low-grade inflammation, hyperglycemia, hyperinsulinemia, and hyperleptinemia, which lead to a weakening of both the innate and adaptive immune responses. In addition, obesity results in anatomical-functional changes by the mechanical obstacle of excessive adipose tissue that blunt the respiratory mechanisms and predisposing to respiratory infections. Subjects with obesity are also at risk of skin folds and sweat more profusely due to the thick layers of subcutaneous fat, favoring the proliferation of microorganisms and slowing the repair of wounds down. All these factors make subjects with obesity more prone to develop nosocomial infections, surgical site, skin and soft tissue infections, bacteremia, urinary tract infections, and mycosis. Furthermore, infections in subjects with obesity have a worse prognosis, frequently prolonging hospitalization time as demonstrated for several flu viruses and recently for COVID-19. Thus, the aim of this manuscript is to provide an overview of the current clinical evidence on the associations between obesity and infectious diseases highlighting physio pathological insights involved in this link.
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http://dx.doi.org/10.1111/obr.13216DOI Listing
June 2021

Could ketogenic diet "starve" cancer? Emerging evidence.

Crit Rev Food Sci Nutr 2020 Dec 4:1-22. Epub 2020 Dec 4.

Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Naples, Italy.

Cancer cells (CCs) predominantly use aerobic glycolysis (Warburg effect) for their metabolism. This important characteristic of CCs represents a potential metabolic pathway to be targeted in the context of tumor treatment. Being this mechanism related to nutrient oxidation, dietary manipulation has been hypothesized as an important strategy during tumor treatment. Ketogenic diet (KD) is a dietary pattern characterized by high fat intake, moderate-to-low protein consumption, and very-low-carbohydrate intake (<50 g), which in cancer setting may target CCs metabolism, potentially influencing both tumor treatment and prognosis. Several mechanisms, far beyond the originally proposed inhibition of glucose/insulin signaling, can underpin the effectiveness of KD in cancer management, ranging from oxidative stress, mitochondrial metabolism, and inflammation. The role of a qualified Nutritionist is essential to reduce and manage the short and long-term complications of this dietary therapy, which must be personalized to the individual patient for the planning of tailored KD protocol in cancer patients. In the present review, we summarize the proposed antitumor mechanisms of KD, the application of KD in cancer patients with obesity and cachexia, and the preclinical and clinical evidence on KD therapy in cancer.
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http://dx.doi.org/10.1080/10408398.2020.1847030DOI Listing
December 2020

A practical nutritional guide for the management of sleep disturbances in menopause.

Int J Food Sci Nutr 2021 Jun 30;72(4):432-446. Epub 2020 Nov 30.

Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Naples, Italy.

Sleep disturbances (SD) represent one of the main symptoms of menopause and they are caused by several factors. Hormonal changes such as the reduction of oestrogen levels and the consequent vasomotor symptoms (VMS) along with psychiatric disorders such as depression and anxiety could contribute to the onset of SD. Furthermore, obesity or through the obstructive sleep apnoea (OSA) could blunt sleep. Moreover, in menopause is usual a reduction in melatonin, that could contribute to SD. Nutritional strategies are paramount because they could contribute to manage menopause-related SD, in particular tackling obesity and overweight. Furthermore, some foods, such as soy, fish, whole grains, vegetables and fruit could decrease symptoms like depression and VMS, correlated with SD in postmenopausal women. Therefore, the aim of this review is to provide an overview of the current evidence on SD in menopause and to provide nutritional strategies for managing SD in this context.
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http://dx.doi.org/10.1080/09637486.2020.1851658DOI Listing
June 2021

Improving sleep disturbances in obesity by nutritional strategies: review of current evidence and practical guide.

Int J Food Sci Nutr 2021 Aug 25;72(5):579-591. Epub 2020 Nov 25.

Department of Clinical Medicine and Surgery, Endocrinology Unit, University Federico II, Naples, Italy.

Over the past decades, there has been an increase in overweight and obesity worldwide rates in both in adult and children. In parallel, it has been reported a worsening of sleep duration and quality. Some studies have shown an association between obesity and sleep disturbances (SD) subjects with obesity have a greater risk of SD. As well as SD influences diet, also food choices have been shown to influence various sleep-related variables, such as duration and quality. For this reason, nutrition could represent an important tool not only to lose weight but also to improve sleep in patients with obesity and sleep disturbances. Thus, the aim of this review is to provide an overview of the studies that assessed the association between obesity and SD and , highlighting possible nutritional advices as a tool to improve sleep in patients with obesity and sleep disturbances.
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http://dx.doi.org/10.1080/09637486.2020.1851659DOI Listing
August 2021

Vitamin D in obesity and obesity-related diseases: an overview.

Minerva Endocrinol (Torino) 2021 Jun 19;46(2):177-192. Epub 2020 Nov 19.

Unit of Endocrinology, Department of Clinical Medicine and Surgery, Collaborating Centers for Obesity Management (COM) of The European Association for the Study of Obesity (EASO), Federico II University Medical School of Naples, Naples, Italy.

Hypovitaminosis D and obesity represent two pandemic conditions sometimes associated with each other. Although it is known that there is a close relationship between these two health problems, the underlying pathophysiological mechanism has not yet been fully clarified. In fact, on the one hand, obesity per se seems to involve low circulating levels of vitamin D due to low sun exposure, physical activity, and intake of foods rich in vitamin D, volumetric dilution and sequestration in the adipose tissue. Conversely, since preadipocytes and adipocytes express the receptors and are involved in the metabolism of vitamin D it would seem that low levels of this vitamin may be involved in adipogenesis and therefore in the development of obesity. This connection is extremely important when considering obesity-related diseases. In fact, low vitamin D levels and severe obesity are significantly associated with some cardio-metabolic risk factors, including high Body Mass Index, waist circumference, blood pressure, impaired lipid and glycemic profile and insulin resistance, as they would seem associated with worse cardiovascular outcomes and higher cancer incidence and mortality. Therefore, the purpose of this review was to examine the recent evidence linking low vitamin D status, obesity and obesity-related diseases, highlighting the scientific achievements and the gaps to be filled with further investigations.
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http://dx.doi.org/10.23736/S0391-1977.20.03299-XDOI Listing
June 2021

Mediterranean diet as tool to manage obesity in menopause: A narrative review.

Nutrition 2020 Nov - Dec;79-80:110991. Epub 2020 Aug 28.

Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Università "Federico II" di Napoli, Naples, Italy; Centro Italiano per la cura e il Benessere del paziente con Obesità (C.I.B.O), Department of Clinical Medicine and Surgery, Endocrinology Unit, University Medical School of Naples, Naples, Italy. Electronic address:

Menopause is a physiological event in a woman's life characterized by the cessation of spontaneous menstrual cycles caused by a reduction in the sex hormones estrogen and progesterone and a consequent increase of gonadotropins, which occurs when the stocks of ovarian follicles end. Weight gain is a common phenomenon in menopause and age of onset is influenced by several factors. Among modifiable risk factors are sedentary lifestyle and unhealthy nutritional patterns, which often result in obesity that in turn contributes to an increase in cardiovascular risk in menopause, mostly through low-grade inflammation. The Mediterranean diet (MedD) is a healthy dietary pattern characterized by an adequate consumption of vegetables, fruits, whole grains, and legumes with a reduction of saturated animal fats in favor of unsaturated vegetable fats and a high intake of bioactive compounds including polyphenols and ω-3 fatty acids with anti-inflammatory and antioxidant potency. Because of its palatability and long-term sustainability, the MedD, especially if hypocaloric, combined with physical activity, has shown promising results in terms of weight loss in individuals with obesity, as well as similar beneficial effects in menopause-related obesity. It has been observed that greater adherence to the MedD in menopause is associated with reduced risk for becoming overweight/obese, better cardiometabolic profile, and an improvement in menopausal symptoms. Although it is necessary to confirm these data with future large intervention trials, the MedD can be considered a safe and healthy approach in the management of menopause-related obesity and its cardiometabolic complications.
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http://dx.doi.org/10.1016/j.nut.2020.110991DOI Listing
June 2021

Mediterranean diet and breast cancer risk: a narrative review.

Minerva Endocrinol 2020 Sep 24. Epub 2020 Sep 24.

Dipartimento di Medicina Clinica e Chirurgia, Unità di Endocrinologia, Università Federico II di Napoli, Napoli, Italia.

Breast cancer is the second most frequent type of cancer worldwide and the most commonly occurring malignancy in women, and its incidence is increasing in most developed and developing countries. There is growing evidence that lifestyle factors, in particular diet may be associated with higher Breast Cancer risk. Some evidence exists regarding the benefit of Mediterranean Diet on reduced risk of Breast Cancer in premenopausal and postmenopausal women. The protective effect of the Mediterranean Diet against the risk of Breast Cancer, is primarily due to principal foods of this nutritional pattern. The principal components of the Mediterranean Diet, such as fruits and vegetables, olive oil, fish and red wine have important antioxidants properties due to their high content of substances like polyphenols, flavonoids, carotenoids and fibers, along with a favourable fatty acid profile, that in turn could reduce the risk of Breast Cancer. Considering the severity of breast cancer and the increasing incidence in the world, there is an increasing interest in promoting prevention strategies in order to reduce the incidence. The aim of this paper is to provide a general overview of the current evidence on the relationship between Breast Cancer and Mediterranean Diet, in premenopausal and postmenopausal women, and to emphasize the potential role of Mediterranean Diet as an effective tool in primary prevention. The possible molecular mechanisms underlying this association will be also pointed out.
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http://dx.doi.org/10.23736/S0391-1977.20.03266-6DOI Listing
September 2020

Very low-calorie ketogenic diet (VLCKD) in patients with psoriasis and obesity: an update for dermatologists and nutritionists.

Crit Rev Food Sci Nutr 2020 Sep 24:1-17. Epub 2020 Sep 24.

Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Naples, Italy.

Psoriasis is a chronic skin immune-mediated disease with systemic pro-inflammatory activation; both genetic and lifestyles factors contribute to its pathogenesis and severity. In this context, nutrition plays a significant role, , in psoriasis' pathogenesis. Obesity is another important risk factor for psoriasis, and weight reduction may improve psoriasis' clinical severity. The excess body weight, particularly visceral fat mass, can affect both drug's pharmacokinetics and pharmacodynamics. Therefore, psoriasis and obesity share a certain degree of synergy, and the chronic inflammatory state represents the basis of this vicious cycle. Evidence reported that nutrition has different impact on the clinical severity of psoriasis, though some specific diets have been more investigated in clinical studies compared to others. Diets with systemic anti-inflammatory properties seem to have a higher effect on improving the clinical severity of psoriasis. Of interest, very-low-calorie ketogenic diet (VLCKD), through the production of ketone bodies, has been associated with both a significant reduction of body weight and inflammatory state. VLCKD leading to both weight loss and reduction of systemic inflammation may decrease the exacerbation of the clinical manifestations or even it may block the trigger of psoriatic disease. This dietary pattern could represent a potential first-line treatment in psoriatic patients with obesity. The review aims to summarize the current evidence regarding VLCKD and psoriasis with specific reference to antioxidant and anti-inflammatory effects of this dietary pattern.
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http://dx.doi.org/10.1080/10408398.2020.1818053DOI Listing
September 2020

Does Sars-Cov-2 threaten our dreams? Effect of quarantine on sleep quality and body mass index.

J Transl Med 2020 08 18;18(1):318. Epub 2020 Aug 18.

Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini 5, 80131, Naples, Italy.

Background: COVID 19-related quarantine led to a sudden and radical lifestyle changes, in particular in eating habits. Objectives of the study were to investigate the effect of quarantine on sleep quality (SQ) and body mass index (BMI), and if change in SQ was related to working modalities.

Materials: We enrolled 121 adults (age 44.9 ± 13.3 years and 35.5% males). Anthropometric parameters, working modalities and physical activity were studied. Sleep quality was evaluated by the Pittsburgh Sleep Quality Index (PSQI) questionnaire. At baseline, the enrolled subjects were assessed in outpatient clinic and after 40 days of quarantine/lockdown by phone interview.

Results: Overall, 49.6% of the subjects were good sleepers (PSQI < 5) at the baseline and significantly decreased after quarantine (p < 0.001). In detail, sleep onset latency (p < 0.001), sleep efficiency (p = 0.03), sleep disturbances (p < 0.001), and daytime dysfunction (p < 0.001) significantly worsened. There was also a significant increase in BMI values in normal weight (p = 0.023), in subjects grade I (p = 0.027) and II obesity (p = 0.020). In all cohort, physical activity was significantly decreased (p = 0.004). However, analyzing the data according gender difference, males significantly decreased physical activity as well as females in which there was only a trend without reaching statistical significance (53.5% vs 25.6%; p = 0.015 and 50.0% vs 35.9%, p = 0.106; in males and females, respectively). In addition, smart working activity resulted in a significant worsening of SQ, particularly in males (p < 0.001).

Conclusions: Quarantine was associated to a worsening of SQ, particularly in males doing smart working, and to an increase in BMI values.
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http://dx.doi.org/10.1186/s12967-020-02465-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7432549PMC
August 2020

Papillary thyroid carcinoma arising in ectopic thyroid tissue within sternocleidomastoid muscle: a review of current literature.

Minerva Endocrinol 2020 Dec 3;45(4):318-325. Epub 2020 Aug 3.

Unit of Endocrinology, Department of Clinical Medicine and Surgery, Federico II University Medical School, Naples, Italy.

The prevalence of ectopic thyroid tissue as consequence of an aberrant migration of thyroid during embryogenesis ranges up to 10% in autopsy studies. The differential diagnosis between the relatively rare occurrence of a primary carcinoma arising in ectopic thyroid tissue and the more frequent presence of cervical lymph node metastasis from papillary thyroid carcinoma (PTC) might represent a difficult challenge in the clinical practice. The clinical relevance of these lesions lies in their risk of hidden primary thyroid cancer. Our intention is to provide in this review the current limited data available and to report an unusual localization of primary PTC arising from an extra-thyroid area, responsible for a solitary cervical mass as initial manifestation. The tumor developed in an ectopic thyroid tissue embedded within the clavicular head of the sternocleidomastoid muscle and was completely separated from the thyroid. Surgical excision of ectopic thyroid tissue with clavicular head of sternocleidomastoid muscle along with total thyroidectomy and central and selective lateral neck dissection were carried out. Histopathology was diagnostic for ectopic PTC and no primary lesions in the thyroid gland neither metastatic lymph nodes were found. Tumor cells were positive for thyroid transcription factor-1and thyroglobulin, and negative for CD56. A postoperative adjuvant radioiodine ablation was given after recombinant human thyroid-stimulating hormone (TSH) stimulation and the post-treatment whole body scan was negative. After the evaluation at six months showing negative neck ultrasound and undetectable thyroglobulin levels, while TSH suppressed and after recombinant human TSH stimulation, the patient was re-evaluated every six months. At two years, the patient remained completely free of disease and is currently on substitutive dose of l-thyroxine. Endocrinologists and neck surgeons must be aware of the rare possibility of primary PTC arising from ectopic thyroid tissue within the sternocleidomastoid muscle.
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http://dx.doi.org/10.23736/S0391-1977.20.03167-3DOI Listing
December 2020

Impact of current anti-psoriatic systemic treatments on male and female fertility: what the endocrinologist needs to know.

Minerva Endocrinol 2020 Jul 23. Epub 2020 Jul 23.

Section of Dermatology, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Fertility is a function of the body that often is overlooked as a site for the expression of the side effects of certain drugs. With the approval of new drugs with a totally innovative mechanism of action, the risk assessment on fertility both in male and female is more difficult. This is particularly true in psoriasis, an invalidating inflammatory skin disease. The estimated prevalence of psoriasis in adults ranged from 0.51% to 11.43%, and in children from 0% to 1.37%, with frequent diagnosis in young patients of childbearing age. With the increasing use of new, predominantly immunosuppressive or biologic drugs for psoriasis, questions frequently arise in clinical practice as to their safety in men and women wishing to procreate. Both psoriatic patients and their physicians are concerned about adverse effects of the disease and its treatment on their future fertility, causing additional concerns in the therapeutic management of these patients. Among anti-psoriatic drugs, conventional therapies are mainly involved in the onset of infertility in both sexes, exerting in some cases toxic effects against reproductive organs. Conversely, biologic agents appear to improve male and female fertility especially when gonadal impairment is related to inflammatory phenomena. There is a lack of review articles of commonly used medications in psoriasis with respect to their potential effects on fertility. This paper aims to provide a practical guide for both dermatologist and endocrinologist in therapeutic management of psoriatic patients of childbearing age, considering the impact of prescribed drugs on their current and future fertility.
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http://dx.doi.org/10.23736/S0391-1977.20.03236-8DOI Listing
July 2020

Sleep disturbances: one of the culprits of obesity-related cardiovascular risk?

Int J Obes Suppl 2020 Jul 20;10(1):62-72. Epub 2020 Jul 20.

Endocrinology Unit, Department of Clinical Medicine and Surgery, University Federico II, Naples, Italy.

Growing evidence suggested that Sleep Disorders (SD) could increase the risk of developing obesity and could contribute to worsen obesity-related cardiovascular risk. Further, obesity has been reported to blunt sleep homeostasis. This happens through several mechanisms. First of all, the excessive adipose tissue at neck and chest levels could represent a mechanical obstacle to breathe. Moreover, the visceral adipose tissue is known to release cytokines contributing to low-grade chronic inflammation that could impair the circadian rhythm. Also, nutrition plays an important role in sleep homeostasis. High fat and/or high carbohydrate diets are known to have a negative impact on both sleep quality and duration. In addition, obesity predisposes to a condition called "" that has a detrimental effect on sleep. SD could increase the risk and/or could contribute to worsen cardiovascular risk usually associated with obesity. The chronic low grade inflammation associated with obesity has been reported to increase the risk of developing hypertension, type 2 diabetes and dyslipidemia. In turn, improving quality of sleep has been reported to improve the management of these cardiovascular risk factors. Thus, the aim of this manuscript is to provide evidence on the association of obesity and SD and on how they could contribute to the risk of developing cardiovascular risk factors such as hypertension, dyslipidemia and type 2 diabetes in obesity.
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http://dx.doi.org/10.1038/s41367-020-0019-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371737PMC
July 2020

What is the best diet for cardiovascular wellness? A comparison of different nutritional models.

Int J Obes Suppl 2020 Jul 20;10(1):50-61. Epub 2020 Jul 20.

Dipartimento di Medicina Clinica e Chirurgia, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini 5, 80131 Naples, Italy.

Cardiovascular diseases (CVD) represent to date the leading cause of mortality in both genders in the developed countries. In this context, a strong need for CVD prevention is emerging through lifestyle modification and nutrition. In fact, several studies linked CVD with unhealthy nutrition, alcohol consumption, stress, and smoking, together with a low level of physical activity. Thus, the primary aim is to prevent and reduce CVD risk factors, such as impaired lipid and glycemic profiles, high blood pressure and obesity. Different types of diet have been, therefore, established to optimize the approach regarding this issue such as the Mediterranean diet, Dietary Approaches to Stop Hypertension diet (DASH), vegetarian diet, ketogenic diet, and Japanese diet. Depending on the diet type, recommendations generally emphasize subjects to increase vegetables, fruits, whole grains, and pulses consumption, but discourage or recommend eliminating red meat, sweets, and sugar-sweetened beverages, along with processed foods that are high in sugar, salt, fat, or low in dietary fiber. In particular, we evaluated and compared the peculiar aspects of these well-known dietary patterns and, thus, this review evaluates the critical factors that increase CVD risk and the potential application and benefits of nutritional protocols to ameliorate dietary and lifestyle patterns for CVD prevention.
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http://dx.doi.org/10.1038/s41367-020-0018-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371887PMC
July 2020

From obesity through gut microbiota to cardiovascular diseases: a dangerous journey.

Int J Obes Suppl 2020 Jul 20;10(1):35-49. Epub 2020 Jul 20.

Unit of Endocrinology, Dipartimento di Medicina Clinica e Chirurgia, Federico II University, 80131 Naples, Italy.

The co-existence of humans and gut microbiota started millions of years ago. Until now, a balance gradually developed between gut bacteria and their hosts. It is now recognized that gut microbiota are key to form adequate immune and metabolic functions and, more in general, for the maintenance of good health. Gut microbiota are established before birth under the influence of maternal nutrition and metabolic status, which can impact the future metabolic risk of the offspring in terms of obesity, diabetes, and cardiometabolic disorders during the lifespan. Obesity and diabetes are prone to disrupt the gut microbiota and alter the gut barrier permeability, leading to metabolic endotoxaemia with its detrimental consequences on health. Specific bacterial sequences are now viewed as peculiar signatures of the metabolic syndrome across life stages in each individual, and are linked to pathogenesis of cardiovascular diseases (CVDs) via metabolic products (metabolites) and immune modulation. These mechanisms have been linked, in association with abnormalities in microbial richness and diversity, to an increased risk of developing arterial hypertension, systemic inflammation, nonalcoholic fatty liver disease, coronary artery disease, chronic kidney disease, and heart failure. Emerging strategies for the manipulation of intestinal microbiota represent a promising therapeutic option for the prevention and treatment of CVD especially in individuals prone to CV events.
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http://dx.doi.org/10.1038/s41367-020-0017-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371682PMC
July 2020

Maternal obesity: focus on offspring cardiometabolic outcomes.

Int J Obes Suppl 2020 Jul 20;10(1):27-34. Epub 2020 Jul 20.

Endocrinology Unit, Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy.

Several human and animal studies have demonstrated that cardiometabolic parameters in infancy, childhood, adolescence and even adulthood are negatively influenced by many factors besides energy imbalance. Interestingly, maternal weight excess both before and during pregnancy seems to be a negative determinant of metabolic and cardiovascular outcomes in the offspring. This review includes both human and animal studies and finally highlights the link between maternal obesity and cardiometabolic disorders in offspring.
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http://dx.doi.org/10.1038/s41367-020-0016-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371867PMC
July 2020

Cardiovascular effects of antiobesity drugs: are the new medicines all the same?

Int J Obes Suppl 2020 Jul 20;10(1):14-26. Epub 2020 Jul 20.

Department of Clinical Medicine and Surgery, Unit of Endocrinology, Federico II University Medical School of Naples, Via Sergio Pansini 5, 80131 Naples, Italy.

Waiting for a definite answer from well-designed randomized prospective clinical trials, the impact of the new antiobesity drugs -liraglutide, bupropion/naltrexone, phentermine/topiramate and lorcaserin- on cardiovascular outcomes remains uncertain. What has been learned from previous experience with older medicines is that antiobesity drugs may influence cardiovascular health not only causing weight reduction but also through direct actions on the cardiovascular system. Therefore, in the present review, we examine what is known, mainly from preclinical investigations, about the cardiovascular pharmacology of the new antiobesity medicines with the aim of highlighting potential mechanistic differences. We will show that the two active substances of the bupropion/naltrexone combination both exert beneficial and unwanted cardiovascular effects. Indeed, bupropion exerts anti-inflammatory effects but at the same time it does increase heart rate and blood pressure by potentiating catecholaminergic neurotransmission, whereas naltrexone reduces TLR4-dependent inflammation and has potential protective effects in stroke but also impairs cardiac adaption to ischemia and the beneficial opioid protective effects mediated in the endothelium. On the contrary, with the only exception of a small increase in heat rate, liraglutide only exerts favorable cardiovascular effects by protecting myocardium and brain from ischemic damage, improving heart contractility, lowering blood pressure and reducing atherogenesis. As far as the phentermine/topiramate combination is concerned, no direct cardiovascular beneficial effect is expected for phentermine (as this drug is an amphetamine derivative), whereas topiramate may exert cardioprotective and neuroprotective effects in ischemia and anti-inflammatory and antiatherogenic actions. Finally, lorcaserin, a selective 5HT receptor agonist, does not seem to exert significant direct effects on the cardiovascular system though at very high concentrations this drug may also interact with other serotonin receptor subtypes and exert unwanted cardiovascular effects. In conclusion, the final effect of the new antiobesity drugs on cardiovascular outcomes will be a balance between possible (but still unproved) beneficial effects of weight loss and "mixed" weight-independent drug-specific effects. Therefore comparative studies will be required to establish which one of the new medicines is more appropriate in patients with specific cardiovascular diseases.
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http://dx.doi.org/10.1038/s41367-020-0015-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371629PMC
July 2020
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