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We evaluated the clinical impact, in daily clinical practice, of sodium-glucose co-transporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP1RA) therapies in patients with type 2 diabetes. Data from 500 unselected consecutive patients were retrospectively analyzed. Only those with a full assessment at baseline (T0) and after 3 (T3), 6 (T6), and 12 (T12) months of treatment with SGLT2i or GLP1RA were included in the study (n = 167). At baseline, patients had a high mean body weight (BW), abdominal circumference (AC), body mass index (BMI), and HOMA index. Despite normal C-peptide values, 39 patients were being treated with insulin (up to 120 IU/day). During therapy, a progressive improvement in BW, BMI, and AC was observed with both the molecules. Fasting glucose and glycated Hb decrease was already significant at T3 in all patients, while the HOMA index selectively improved with SGLT2i therapy. Renal function parameters remained stable regardless of the drug used. Finally, SGLT2i reduced serum uric acid and improved the lipid profile, while GLP1RA reduced serum levels of liver enzymes. Both the therapeutic regimens allowed a significant reduction or complete suspension of unnecessary insulin therapies. Our real life data confirm the results obtained from randomized clinical trials and should be taken as a warning against inappropriate use of insulin in patients with preserved β-cell function.

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) induce body weight loss, but their effect on skeletal muscle mass (SMM) and strength needs to be better elucidated., Objectives: This study aimed to evaluate the effects of SGLT2i on SMM in a real-life population setting of patients with type 2 diabetes (T2D). Secondary outcomes included changes in liver steatosis and in anthropometric and glucometabolic parameters., Methods: Seventy-one patients were treated with SGLT2is as an add-on to metformin for 52 consecutive weeks. Visits were scheduled at baseline (T0) and after 6 (T6) and 12 months of therapy (T12) and included the checking of laboratory tests, measurement of anthropometric parameters, bioimpedance analysis of body composition, and abdominal ultrasound (US)., Results: Fat mass (FM) and visceral adipose tissue (VAT) progressively decreased compared to the baseline (FM: -2.9 ± 0.6 kg at T6; -2.8 ± 0.6 kg at T12; VAT: -0.3 ± 0.1 L at T6; -0.4 ± 0.1 L at T12; all p < 0.01). Changes in SMM were less pronounced (-0.4 ± 0.3 kg at T6, ns; -0.7 ± 0.4 kg at T12, p < 0.05), yielding a beneficial increase in the SMM/FM ratio (+0.3 ± 0.05 at T6 and +0.2 ± 0.05 at T12, all p < 0.01). No significant changes in sarcopenia, sarcopenic obesity, fat-free mass, muscle strength, and water compartments were observed at the end of the follow-up period. Anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and biometric indices and US grading of hepatic steatosis improved throughout this study., Conclusions: In a real-life setting, SGLT2i therapy is associated with weight loss attributable to FM rather than SMM loss without any relevant deterioration in muscle strength. In addition, SGLT2is proved to have beneficial effects on steatotic liver disease.

Subclinical hypothyroidism (SH), defined as increased serum thyroid-stimulating hormone (TSH) with normal free T4 (fT4) levels, is frequently observed in the general population. Prevalence ranges from 0.6% to 1.8% in the adult population, depending on age, sex, and iodine intake. Several studies reported a worse prognosis in patients with heart failure with reduced ejection fraction (HFrEF) and SH, but they considered heterogeneous populations suffering mainly from severe SH. Aim of this study was to evaluate if SH was independently associated with the occurrence of cardiovascular death considering 30 months of follow-up. 277 HFrEF patients enrolled in the prospective, multicenter, observational T.O.S.CA. (Terapia Ormonale Scompenso CArdiaco) registry, were included in this analysis. Patients were divided into two groups according to the presence of SH (serum TSH levels > 4.5 mIU/L with normal fT4 levels). Data regarding clinical status, echocardiography, and survival were analyzed. Twenty-three patients displayed SH (87% mild vs 13% severe), while 254 were euthyroid. No differences were found in terms of age, sex, HF etiology, and left ventricular ejection fraction. When compared with the euthyroid group, SH patients showed higher TSH levels (7.7 ± 4.1 vs 1.6 ± 0.9, p < 0.001), as expected, with comparable levels of fT4 (1.3 ± 0.3 vs 1.3 ± 0.3, p = NS). When corrected for established predictors of poor outcome in HF, the presence of SH resulted to be an independent predictor of cardiovascular mortality (HR: 2.96; 5-95% CI:1.13-7.74; p = 0.03). Since thyroid tests are widely available and inexpensive, they should be performed in HF patients to detect subclinical disorders, evaluate replacement therapy, and improve prognosis., (© 2024. The Author(s).)

Background: One hundred years have passed since the discovery of insulin, which is one of the most relevant events of the 20th century. This period resulted in extraordinary progress in the development of novel molecules to improve glucose control, simplify the insulin regimen, and ameliorate the quality of life. In late March 2024, the first once-weekly basal analog Icodec was approved for diabetes mellitus, generating high expectations. Our aim was to systematically review and meta-analyze the efficacy and safety of Icodec compared to once-daily insulin analogs in type 1 (T1D) and type 2 diabetes (T2D)., Methods: PubMed/MEDLINE, Cochrane Library, and ClinicalTrials.gov were searched for randomized clinical trials (RCTs). Studies were included for the synthesis according to the following prespecified inclusion criteria: uncontrolled T1D or T2D, age ≥ 18 years, insulin Icodec vs. active comparators (Degludec U100, Glargine U100, Glargine U300, and Detemir), phase 3, multicenter, double-blind or open-label RCTs, and a study duration ≥ 24 weeks., Results: The systematic review included 4347 patients with T1D and T2D inadequately controlled (2172 randomized to Icodec vs. 2175 randomized to once-daily basal analogs). Icodec, compared to once-daily basal analogs, slightly reduced the levels of glycated hemoglobin (HbA1c) with an estimated treatment difference (ETD) of -0.14% [95%CI -0.25; -0.03], p = 0.01, and I 2 68%. Patients randomized to Icodec compared to those on once-daily basal analogs had a greater probability to achieve HbA1c < 7% without clinically relevant or severe hypoglycemic events in 12 weeks from randomization with an estimated risk ratio (ERR) of 1.17, [95%CI 1.01, 1.36], p = 0.03, and I 2 66%. We did not find a difference in fasting glucose levels, time in range, and time above range between Icodec and comparators. Icodec, compared to once-daily basal analogs, resulted in a slight but statistically significant weight gain of 0.62 kg [95%CI 0.25; 0.99], p = 0.001, and I 2 25%. The frequency of hypoglycemic events (ERR 1.16 [95%CI 0.95; 1.41]), adverse events (ERR 1.04 [95%CI 1.00; 1.08]), injection-site reactions (ERR 1.08 [95%CI 0.62; 1.90]), and the discontinuation of treatments were similar between the two groups. Icodec was found to work better when used in a basal-only than basal-bolus regimen with an ETD in HbA1c of -0.22%, a probability of achieving glucose control of +33%, a probability of achieving glucose control without clinically relevant or severe hypoglycemia of +28%, more time spent in target (+4.55%) and less time spent in hyperglycemia (-5.14%). The risk of clinically relevant or severe hypoglycemic events was significantly higher when background glinides and sulfonylureas were added to basal analogs (ERR 1.42 [95%CI 1.05; 1.93])., Conclusion: Insulin Icodec is substantially non-inferior to once-daily insulin analogs in T2D, either insulin-naïve or insulin-treated. However, Icodec works slightly better than competitors when used in a basal-only rather than basal-bolus regimen. Weight gain and hypoglycemic risk are substantially low but not negligible. Patients' education, adequate lifestyle and pharmacological interventions, and appropriate therapy adjustments are essential to minimize risks. This systematic review is registered as PROSPERO CRD42024568680.

Polyphenols are secondary metabolites found in plants, foods, and drinks, occurring in small quantities and showcasing antioxidant and anti-inflammatory qualities. The primary polyphenols consist of flavonoids, phenolic acids, stilbenes, and lignans. However, there is currently no comprehensive quantitative analysis of epidemiological data on overall death rates. This systematic review with meta-analysis aims to identify the exposure-response relationship between dietary polyphenol intake and all-cause mortality. The literature was reviewed from its earliest study to May 2024, utilizing six distinct electronic databases. No specific criteria were used to choose participants based on the recruiting environment, their general health condition, country, or ethnicity. The inclusion criteria for studies were as follows: a longitudinal design, exposure to dietary polyphenols, all-cause mortality as the outcome, and hazard risk (HR) as the impact measure. The Newcastle-Ottawa Scale was used to evaluate the methodological rigor of the study. The hazard risks (HRs) and 95% confidence intervals (CIs) were estimated by pooling data using common effects models. A protocol has been registered on PROSPERO with the identification number CRD42024545524. The meta-analysis comprised seven cohort studies that involved 178,657 adult people aged 18 years and older. These studies examined the relationship between total dietary polyphenol consumption and the risk of all-cause death. The recruitment settings exclusively used community-based approaches, with a preference for Europe (71%) in terms of geographic distribution. The study's quality was assessed to be moderate to high. The meta-analysis showed consistent evidence that increased dietary exposure to polyphenols reduces the risk of all-cause mortality by 7% (HR 0.93, 95% CI 0.91-0.95, I 2 : 48%). Pooled data from the available evidence consistently show that individuals exposed to an antioxidant diet rich in polyphenol sources may be at lower risk of all-cause mortality.

Introduction: Perchlorates are ionic inhibitors antagonizing iodine transport into thyrocytes, hampering thyroid hormone synthesis. Nevertheless, perchlorates are not considered as first-line treatment in hyperthyroidism and thyrotoxicosis as compared to other pharmacological and non-pharmacological interventions., Aim: Reassessing the therapeutic role of perchlorates in hyperthyroidism and thyrotoxicosis throughout a systematic review of the Literature., Methods: Guidelines were searched and examined to summarize current recommendations on the use of perchlorates in the management of hyperthyroidism. Randomized and non-randomized clinical trials were also searched and reviewed to summarize the efficacy/effectiveness and safety of perchlorates in hyperthyroidisms and thyrotoxicosis., Results: The management of specific forms of hyperthyroidism was considered, including Graves' disease (GD) in non-pregnant adults, hyperthyroidisms in pregnancy, iodine media contrast-induced hyperthyroidism, amiodarone-induced hyperthyroidisms, and thyroid storm. Most of the reported studies had remarkable limitations in terms of study design (non-controlled trials, lack of blinding), low number of participants, and the lack of clinically relevant endpoints, such as cardiovascular events, cardiovascular mortality, and teratogenicity. Overall, perchlorates could be considered a second-line treatment after thionamides, radioiodine, and total thyroidectomy in both GD and hyperthyroidisms in pregnancy. The therapeutic potential of perchlorates alone or in combination with other agents could be considered a second-line treatment of iodine-related hyperthyroidisms and thyroid storm., Conclusion: Despite the low level of evidence, perchlorates could be considered in such specific forms of thyroid disorders, including iodine-induced hyperthyroidism and thyroid storm., (© 2024. The Author(s).)

Introduction: Erectile dysfunction (ED) represents the major cause of male sexual dysfunction, which is often associated with obesity, diabetes mellitus, atherosclerotic cardiovascular disease, and cigarette smoking. Peyronie's disease is a chronic disorder associated with irreversible fibrotic damage of the tunica albuginea leading to ED, painful erection, coital disturbance, and physical and social complaints. Both conditions are characterized by chronic inflammation, oxidative stress, and significant changes in intracavernous hydrodynamics. In this scenario, oxidized lipoproteins, M1-polarized macrophages, proinflammatory cytokines (such as the tumor necrosis factor α), endothelial nitric oxide synthase, penile smooth muscle cells, and toll-like receptors represent the main triggers of the inflammatory process in ED. Phosphodiesterase-5 inhibitors are the most common treatment for ED. This treatment is used intermittently, as it is conceived as a symptomatic and not curative therapy. Moreover, not all patients respond to phosphodiesterase-5 inhibitors (35%-85%), particularly those with dysmetabolic phenotypes. Additional or alternative treatments are therefore desirable, mostly in refractory cases., Objectives: In this review, we describe the immune-mediated pathogenesis of ED and Peyronie's disease (PD). In our literature search we placed particular emphasis on potentially practical therapeutic approaches, including natural products (such as polyphenols), due to their anti-inflammatory and antioxidant activities, stem cell therapy, and platelet-derived preparations., Methods: We searched PubMed/MEDLINE, Web of Science, Scopus, Cochrane Library, Google Scholar, and institutional websites. Original studies, narrative reviews, systematic reviews, and meta-analyses written in English were searched, screened, and selected., Results: In animal models of ED and PD, therapeutic approaches, including anti-inflammatory and antioxidant agents, stem cell therapy, and platelet-derived preparations, have provided positive results, including improved penile function, reduced inflammation and oxidative stress, and promotion of tissue repair. However, clinical evidence of improvement in human patients is still insufficient., Conclusion: Promising results for treating ED and PD have been shown in preclinical and pilot clinical studies, but specific clinical trials are needed to validate the efficacy of these therapeutic approaches in men with ED., (© The Author(s) 2024. Published by Oxford University Press on behalf of The International Society of Sexual Medicine.)

Background: The neuropeptide oxytocin (OT) is crucial in several conditions, such as lactation, parturition, mother-infant interaction, and psychosocial function. Moreover, OT may be involved in the regulation of eating behaviors., Methods: This review briefly summarizes data concerning the role of OT in eating behaviors. Appropriate keywords and medical subject headings were identified and searched for in PubMed/MEDLINE. References of original articles and reviews were screened, examined, and selected., Results: Hypothalamic OT-secreting neurons project to different cerebral areas controlling eating behaviors, such as the amygdala, area postrema, nucleus of the solitary tract, and dorsal motor nucleus of the vagus nerve. Intracerebral/ventricular OT administration decreases food intake and body weight in wild and genetically obese rats. OT may alter food intake and the quality of meals, especially carbohydrates and sweets, in humans., Discussion: OT may play a role in the pathophysiology of eating disorders with potential therapeutic perspectives. In obese patients and those with certain eating disorders, such as bulimia nervosa or binge/compulsive eating, OT may reduce appetite and caloric consumption. Conversely, OT administered to patients with anorexia nervosa may paradoxically stimulate appetite, possibly by lowering anxiety which usually complicates the management of these patients. Nevertheless, OT administration (e.g., intranasal route) is not always associated with clinical benefit, probably because intranasally administered OT fails to achieve therapeutic intracerebral levels of the hormone., Conclusion: OT administration could play a therapeutic role in managing eating disorders and disordered eating. However, specific studies are needed to clarify this issue with regard to dose-finding and route and administration time., (© 2023. The Author(s).)

Introduction: The pharmacological management of erectile dysfunction (ED) in type 2 diabetes (T2D) is challenging as ED has a multifactorial etiology. The therapeutic potential of certain antihyperglycemic medications, such as glucagon-like peptide 1 receptor agonists (GLP-1RAs), has yet to be entirely studied in this setting., Material and Methods: A retrospective cohort study was conducted on 108 outpatients (median age 60 [56, 65] years) with T2D complaining of ED. Data were extracted from a database referring to patients with a 1-year follow-up on stable treatment with metformin alone (n = 45) and GLP-1RAs as an add-on to metformin (n = 63). Erectile function was assessed by the 5-item International Index of Erectile Function (IIEF5) at baseline and after 1 year of stable treatment . Values were compared between baseline (T0) and after 12 months of treatment (T12)., Results: ED was confirmed in all at baseline, with an IIEF5 score range between 13 and 19 points. After 12 months of treatment, glucose management was better in patients treated with GLP-1RAs plus metformin (HbA1c T0: 8.3 ± 0.2 vs. HbA1c T12: 7% ± 0.3%, p < 0.0001) than in those on metformin alone (HbA1c T0: 7 ± 0.5 vs. HbA1c T12: 7.3 ± 0.4, p = 0.0007). GLP-1RAs plus metformin over metformin alone resulted in a significant weight loss (-5.82 ± 0.69 kg, p < 0.0001), reduction in waist circumference (-4.99 ± 0.6 cm, p < 0.0001), improvement in HbA1c (-0.56% ± 0.13%, p < 0.0001), and fasting plasma glucose (-25.54 ± 3.09 mg/dL, p < 0.0001), increase in total (+41.41 ± 6.11 ng/dL, p < 0.0001) and free (0.44 ± 0.09 ng/dL, p < 0.0001) testosterone levels, and gain in self-reported erectile function (IIEF5 score: +2.26 ± 0.26, p < 0.0001). The gain in the IIEF5 score was more relevant in patients with higher baseline IIEF5 score (estimated coefficient: 0.16 ± 0.08, p = 0.045), those having carotid stenosis (0.50 ± 0.24, p = 0.045), and showing weight loss from baseline (-0.08 ± 0.03, p = 0.013). The leading determinant of the final IIEF5 score was a 1-year treatment with GLP-1RAs plus metformin over metformin alone (2.74 ± 0.53, p < 0.0001)., Discussion: GLP-1RAs plus metformin over metformin alone improved ED regardless of different background characteristics of patients and partially irrespective of therapeutic targets achieved after 12 months of treatment. GLP-1RAs may have induced positive vasculature effects, resulting in improved erectile function in T2D., Conclusion: Due to the retrospective nature of the study, a potential cause-effect relationship between the use of GLP-1RAs plus metformin over metformin alone in improving ED cannot be verified and confirmed. Randomized clinical trials are needed to provide evidence supporting the use of GLP-1RAs for treating ED in T2D., (© 2023 The Authors. Andrology published by Wiley Periodicals LLC on behalf of American Society of Andrology and European Academy of Andrology.)

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to some metabolic disorders, such as central obesity and type 2 diabetes (T2D). Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide, may have therapeutic roles in MASLD associated with T2D. This study aims to investigate the molecular mechanisms underlying the effectiveness of semaglutide on MASLD in terms of progression from liver steatosis to fibrosis. We characterized exosomes from ten patients with type 2 diabetes (T2D) before (T0) and after 12 months (T12) of treatment with once-weekly subcutaneous semaglutide. Six of ten patients were considered responders to therapy (R) based on MASLD severity downgrading by at least one class according to a validated ultrasonographic (US) score. Normal hepatocytes (HEPA-RG) and stellate (LX-2) cells were challenged with exosomes from R and NR patients, isolated before and after 12 months of therapy. Exosomes from both R and NR patients isolated at T0 significantly affected LX-2 viability. After 12 months of treatment, only those isolated from R patients restored cell viability, whereas those from NR patients did not. No effects were observed on HEPA-RG cells. Exosomes at T12 from R but not from NR patients significantly decreased the production of α-SMA, a marker of LX-2 activation, a liver stellate cell model, and ph-SMAD2 and CTGF, involved in fibrosis processes. TGF-β1 was not modulated by the exosomes of R and NR patients. As a downstream effect, Vimentin, Collagen 1A1, and Fibronectin extracellular matrix components were also downregulated, as measured by droplets digital PCR. In conclusion, these results shed light on the potential effectiveness of semaglutide in improving liver fibrosis in MASLD.

Background: Chronic stress is a condition of pressure on the brain and whole body, which in the long term may lead to a frank disease status, even including type 2 diabetes (T2D). Stress activates the hypothalamus-pituitary-adrenal axis with release of glucocorticoids (GCs) and catecholamines, as well as activation of the inflammatory pathway of the immune system, which alters glucose and lipid metabolism, ultimately leading to beta-cell destruction, insulin resistance and T2D onset. Alteration of the glucose and lipid metabolism accounts for insulin resistance and T2D outcome. Furthermore, stress-related subversion of the intestinal microbiota leads to an imbalance of the gut-brain-immune axis, as evidenced by the stress-related depression often associated with T2D. A condition of generalized inflammation and subversion of the intestinal microbiota represents another facet of stress-induced disease. In fact, chronic stress acts on the gut-brain axis with multiorgan consequences, as evidenced by the association between depression and T2D. Oxidative stress with the production of reactive oxygen species and cytokine-mediated inflammation represents the main hallmarks of chronic stress. ROS production and pro-inflammatory cytokines represent the main hallmarks of stress-related disorders, and therefore, the use of natural antioxidant and anti-inflammatory substances (nutraceuticals) may offer an alternative therapeutic approach to combat stress-related T2D. Single or combined administration of nutraceuticals would be very beneficial in targeting the neuro-endocrine-immune axis, thus, regulating major pathways involved in T2D onset. However, more clinical trials are needed to establish the effectiveness of nutraceutical treatment, dosage, time of administration and the most favorable combinations of compounds. Therefore, in view of their antioxidant and anti-inflammatory properties, the use of natural products or nutraceuticals for the treatment of stress-related diseases, even including T2D, will be discussed. Several evidences suggest that chronic stress represents one of the main factors responsible for the outcome of T2D., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The initial phases of the COVID-19 pandemic posed a real need for clinicians to identify patients at risk of poor prognosis as soon as possible after hospital admission., Aims: The study aimed to assess the role of baseline anamnestic information, clinical parameters, instrumental examination, and serum biomarkers in predicting adverse outcomes of COVID-19 in a hospital setting of Internal Medicine., Methods: Fifty-two inpatients consecutively admitted to the Unit of Internal Medicine "Baccelli," Azienda Ospedaliero - Universitaria Policlinico of Bari (February 1 - May 31, 2021) due to confirmed COVID-19 were grouped into two categories based on the specific outcome: good prognosis (n=44), patients discharged at home after the acute phase of the infection; poor prognosis, a composite outcome of deaths and intensive care requirements (n=8). Data were extracted from medical records of patients who provided written informed consent to participate., Results: The two study groups had similar demographic, anthropometric, clinical, and radiological characteristics. Higher interleukin 6 (IL-6) levels and leucocyte count, and lower free triiodothyronine (fT 3 ) levels were found in patients with poor than those with good prognosis. Higher IL-6 levels and leucocyte count, lower fT 3 concentration, and pre-existing hypercholesterolemia were independent risk factors of poor outcomes in our study population. A predicting risk score, built by assigning one point if fT 3 < 2 pg/mL, IL-6 >25 pg/mL, and leucocyte count >7,000 n/mm 3 , revealed that patients totalizing at least 2 points by applying the predicting score had a considerably higher risk of poor prognosis than those scoring <2 points (OR 24.35 (1.32; 448), p = 0.03). The weight of pre-existing hypercholesterolemia did not change the risk estimation., Conclusion: Four specific baseline variables, one anamnestic (pre-existing hypercholesterolemia) and three laboratory parameters (leucocyte count, IL-6, and fT3), were significantly associated with poor prognosis as independent risk factors. To prevent adverse outcomes, the updated 4-point score could be useful in identifying at-risk patients, highlighting the need for specific trials to estimate the safety and efficacy of targeted treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: The prevalence of hypothyroidism increases along with aging, resulting in one of the most common comorbidities among patients over 75 years. The leading causes of hypothyroidism in older adults are iatrogenic, Hashimoto's thyroiditis, and medications. The narrative review aimed to discuss the clinical characteristics of hypothyroidism in older adults and the impact of hormonal replacement therapy on survival rates. Thyroid function declines over time due to physiological changes in the thyroid stimulating hormone signaling, iodine absorption and metabolism, thyroid hormone metabolism, and activity at peripheral sites. A serum TSH value over the upper limit of the normal reference range is not necessarily attributable to hypothyroidism. However, an appropriate diagnostic work-up is required to rule out true hypothyroidism and discriminate the etiology (i.e., thyroid autoimmune diseases, iodine deficiency, drug-induced hypothyroidism). Levothyroxine treatment should be considered in cases of overt hypothyroidism. A complete risk-to-benefit assessment, particularly considering the overall health status, life expectancy, cognitive function, mood, and cardiovascular and neurological background, should be considered before treating subclinical hypothyroidism with more potential benefits in patients under 75 years old. Levothyroxine formulations facilitating hormone absorption and increasing compliance to long-term treatment should be preferred. TSH target should usually be set over 3 mIU/ml. Defining optimal diagnostic approaches and targeted therapeutic strategies should be considered in the personalized management of aged patients with hypothyroidism., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Sarcopenia is an age-related clinical complaint characterized by the progressive deterioration of skeletal muscle mass and strength over time. Type 2 diabetes (T2D) is associated with faster and more relevant skeletal muscle impairment. Both conditions influence each other, leading to negative consequences on glycemic control, cardiovascular risk, general health status, risk of falls, frailty, overall quality of life, and mortality. PubMed/Medline, Scopus, Web of Science, and Google Scholar were searched for research articles, scientific reports, observational studies, clinical trials, narrative and systematic reviews, and meta-analyses to review the evidence on the pathophysiology of di-abetes-induced sarcopenia, its relevance in terms of glucose control and diabetes-related outcomes, and diagnostic and therapeutic challenges. The review comprehensively addresses key elements for the clinical definition and diagnostic criteria of sarcopenia, the pathophysiological correlation be-tween T2D, sarcopenia, and related outcomes, a critical review of the role of antihyperglycemic treatment on skeletal muscle health, and perspectives on the role of specific treatment targeting myokine signaling pathways involved in glucose control and the regulation of skeletal muscle metabolism and trophism. Prompt diagnosis and adequate management, including lifestyle inter-vention, health diet programs, micronutrient supplementation, physical exercise, and pharmaco-logical treatment, are needed to prevent or delay skeletal muscle deterioration in T2D.

Dopamine regulates several functions, such as voluntary movements, spatial memory, motivation, sleep, arousal, feeding, immune function, maternal behaviors, and lactation. Less clear is the role of dopamine in the pathophysiology of type 2 diabetes mellitus (T2D) and chronic complications and conditions frequently associated with it. This review summarizes recent evidence on the role of dopamine in regulating insular metabolism and activity, the pathophysiology of traditional chronic complications associated with T2D, the pathophysiological interconnection between T2D and chronic neurological and psychiatric disorders characterized by impaired dopamine activity/metabolism, and therapeutic implications. Reinforcing dopamine signaling is therapeutic in T2D, especially in patients with dopamine-related disorders, such as Parkinson's and Huntington's diseases, addictions, and attention-deficit/hyperactivity disorder. On the other hand, although specific trials are probably needed, certain medications approved for T2D (e.g., metformin, pioglitazone, incretin-based therapy, and gliflozins) may have a therapeutic role in such dopamine-related disorders due to anti-inflammatory and anti-oxidative effects, improvement in insulin signaling, neuroinflammation, mitochondrial dysfunction, autophagy, and apoptosis, restoration of striatal dopamine synthesis, and modulation of dopamine signaling associated with reward and hedonic eating. Last, targeting dopamine metabolism could have the potential for diagnostic and therapeutic purposes in chronic diabetes-related complications, such as diabetic retinopathy.

Background: Type 2 diabetes (T2D) is a chronic disease that negatively affects vascular health. A careful assessment of chronic complications, including microcirculation, is mandatory. The computerized nailfold video-capillaroscopy (CNVC) accurately examines the nailfold microvasculature, but its suitability in T2D is currently under investigation., Aims: To describe nailfold microvasculature in T2D patients regarding the level of glucose control and chronic microvascular and macrovascular complications., Methods: This is a cross-sectional study on 102 consecutive and unselected outpatients with T2D who had undergone CNVC examination. The examination was carried out by using an electronic video-capillaroscope with 300x magnification. Capillaroscopic appearance and capillary changes were described according to well-established parameters. Capillaroscopic parameters were compared between patients with poor glucose control (HbA1c ≥7%) and those with better glucose control (HbA1c <7%) and between patients with chronic complications and those without. Chronic complications were deduced from the anamnestic, laboratory, and instrumental data and the five-item International Index of Erectile Function (IIEF-5) questionnaire., Results: Nailfold capillaries in patients with HbA1c ≥7% were thicker (p = .019) and longer (p = .021) than in those with better glucose control. Ectasias (p = .017) and microaneurysms (p = .045) were more frequently observed in patients with HbA1c ≥7.0% than those with HbA1c <7.0%. Patients with ED, compared to those without, had a lower frequency of bizarre-shaped capillaries (p = .02). Microaneurysms (p = .02) were more frequently described in patients with carotid stenosis (>20%) than those without., Conclusion: Relevant nailfold microvascular alterations were observed in T2D, most of which were associated with poor glycemic control, ED, and carotid stenosis. Further investigation is needed to recognize the role of CNVC in predicting the onset and evolution of chronic complications and monitoring the effectiveness of antihyperglycemic treatments on microcirculation., (© 2023 The Authors. Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have changed considerably the management of type 2 diabetes (T2D). However, recently published data from retrospective cohort studies suggest that chronic exposure to GLP-1RAs in T2D may increase the risk of papillary and medullary thyroid cancer. In this perspective, the role of the incretin system in thyroid carcinogenesis has been reviewed and critically commented on, aiming to understand if the time has arrived to be concerned about the risk. Although evidence suggested, speculative hypotheses should be verified, and further studies are urgently needed to clarify the issue.

Background: Oral semaglutide is the first glucagon-like peptide-1 receptor agonist (GLP-1RA) designed for oral administration; it offers a promising opportunity to facilitate an early approach to Type 2 Diabetes (T2D). The study aimed to evaluate, in a real-life setting, the effects of oral semaglutide on the body composition of patients with T2D after 26 weeks of therapy., Methods: Thirty-two patients with T2D were evaluated at baseline (T0) and after three (T3) and six (T6) months of therapy with oral semaglutide. At each time point, body composition was assessed using a phase sensitive bioimpedance analyzer. Clinical, anthropometric and laboratory parameters, and the main biometric surrogates of liver steatosis and fibrosis, were also analyzed and compared., Results: A significant and early reduction in anthropometric and glucometabolic parameters, alanine aminotransferase, Fatty Liver Index, and Fat Mass was observed. Visceral Adipose Tissue (VAT) decreased, while Fat Free Mass and Skeletal Muscle Mass (SMM) were preserved during therapy, resulting in a beneficial increase in the SMM/VAT ratio. Finally, an overall improvement in body fluid distribution was observed., Conclusion: Our real-world data confirm the clinical efficacy of oral semaglutide and highlight its ability to improve the nutritional status of patients with T2D., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Volpe, Lisco, Fanelli, Racaniello, Colaianni, Lavarra, Triggiani, Crudele, Triggiani, Sabbà, De Pergola and Piazzolla.)

Background: Erectile function depends on a complex interaction between demographic, metabolic, vascular, hormonal, and psychological factors that trigger erectile dysfunction (ED). In the present study we carried out a cross-sectional study assessing the impact of non-communicable chronic diseases (NCDs), male hypogonadism, and demographic factors in characterizing men with ED. Four hundred thirty-three consecutive outpatients with ED were extracted from the electronic database from January 2017 to December 2019. The International Index of Erectile Function (IIEF) 5 score was used to diagnose ED and stratify its severity, standardized values of serum testosterone (10.5 nM/L) and luteinizing hormone (LH 9.4 IU/L) to diagnose and classify male hypogonadism and the Charlson Comorbidity Index (CCI) to weigh the role of each NCD on ED., Results: Forty-six percent of participants were eugonadal (EuG), 13% had organic hypogonadism (OrH), and the remaining 41% had functional hypogonadism (FuH). Hypogonadal men had a significantly lower IIEF 5 score (p < .0001) than EuG. FuH had a higher CCI than OrH and EuG (all p < .0001). In a multivariable model, only free T (FT) and Sex Hormone Binding Globulin (SHBG) showed a direct correlation with the IIEF 5 score (all p < .0001). Age and CCI had an inverse correlation with IIEF 5 score (all p < .0001)., Conclusion: Serum FT, SHBG, and CCI are the leading determinants of ED severity. Besides overt hypogonadism, a relevant burden of severe NTCDs in middle-aged or older adults features the patient's characteristics who will suffer from severe ED. Appropriate clinical approaches and, when necessary, treatments are required in these clusters of patients., (© 2023. The Author(s).)

The thyroid gland requires iodine to synthesize thyroid hormones, and iodine deficiency results in the inadequate production of thyroxine and related thyroid, metabolic, developmental, and reproductive disorders. Iodine requirements are higher in infants, children, and during pregnancy and lactation than in adult men and non-pregnant women. Iodine is available in a wide range of foods and water and is susceptible to almost complete gastric and duodenal absorption as an iodide ion. A healthy diet usually provides a daily iodine consumption not exceeding 50% of the recommended intake. Iodine supplementation is usually necessary to prevent iodine deficiency disorders (IDDs), especially in endemic areas. The community-based strategy of iodine fortification in salt has eradicated IDDs, such as endemic goiter and cretinism, in countries providing adequate measures of iodine prophylaxis over several decades in the 20th century. Iodized salt is the cornerstone of iodine prophylaxis in endemic areas, and the continuous monitoring of community iodine intake and its related clinical outcomes is essential. Despite the relevant improvement in clinical outcomes, subclinical iodine deficiency persists even in Western Europe, especially among girls and women, being an issue in certain physiological conditions, such as pregnancy and lactation, and in people consuming unbalanced vegetable-based or salt-restricted diets. Detailed strategies to implement iodine intake (supplementation) could be considered for specific population groups when iodized salt alone is insufficient to provide adequate requirements.

Background: The detection of thyroid nodules has been increasing over time, resulting in an extensive use of fine-needle aspiration (FNA) and cytology. Tailored methods are required to improve the management of thyroid nodules, including algorithms and web-based tools., Study Aims: To assess the performance of the Thyroid Nodule App (TNAPP), a web-based, readily modifiable, interactive algorithmic tool, in improving the management of thyroid nodules., Methods: One hundred twelve consecutive patients with 188 thyroid nodules who underwent FNA from January to December 2016 and thyroid surgery were retrospectively evaluated. Neck ultrasound images were collected from a thyroid nodule registry and re-examined to extract data to run TNAPP. Each nodule was evaluated for ultrasonographic risk and suitability for FNA. The sensitivity, specificity, positive and negative predictive values, and overall accuracy of TNAPP were calculated and compared to the diagnostic performance of the other two algorithms by the American Association of Clinical Endocrinology/American College of Endocrinology/Associazione Medici Endocrinologi ( AACE/ACE/AME), which it was derived from the American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS)., Results: TNAPP performed better in terms of sensitivity (>80%) and negative predictive value (68%) with an overall accuracy of 50.5%, which was similar to that found with the AACE/ACE/AME algorithm. TNAPP displayed a slightly better performance than AACE/ACE/AME and ACR TI-RADS algorithms in selectively discriminating unnecessary FNA for nodules with benign cytology (TIR 2 - Bethesda class II: TNAPP 32% vs. AACE/ACE/AME 31% vs. ACR TI-RADS 29%). The TNAPP reduced the number of missed diagnoses of thyroid nodules with suspicious and highly suspicious cytology (TIR 4 + TIR 5 - Bethesda classes V + VI: TNAPP 18% vs. AACE/ACE/AME 26% vs. ACR TI-RADS 20.5%). A total of 14 nodules that would not have been aspirated were malignant, 13 of which were microcarcinomas (92.8%)., Discussion: The TNAPP algorithm is a reliable, easy-to-learn tool that can be readily employed to improve the selection of thyroid nodules requiring cytological characterization. The rate of malignant nodules missed because of inaccurate characterization at baseline by TNAPP was lower compared to the other two algorithms and, in almost all the cases, the tumors were microcarcinomas. TNAPP's use of size >20 mm as an independent determinant for considering or recommending FNA reduced its specificity., Conclusion: TNAPP performs well compared to AACE/ACE/AME and ACR-TIRADS algorithms. Additional retrospective and, ultimately, prospective studies are needed to confirm and guide the development of future iterations that incorporate different risk stratification systems and targets for diagnosing malignancy while reducing unnecessary FNA procedures., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Triggiani, Lisco, Renzulli, Frasoldati, Guglielmi, Garber and Papini.)

Background: Insulin resistance (IR) and type 2 diabetes mellitus (T2D) are known to affect the progression of chronic heart failure (CHF), but little evidence exists about the impact of IR and T2D on right ventricular dysfunction and exercise tolerance. Insights from the T.O.S.C.A. Registry: Echocardiographic hallmarks and cardiopulmonary exercise test (CPET) results were evaluated at baseline and after an average time of 36 months. T2D patients exhibited a greater intraventricular septum (IVS) thickness (11 ± 2 mm, 10 ± 2 mm, 10 ± 2 mm, in T2D, IR, and EU, respectively; p<.05) and LV wall thickness (0.34 ± 0.1, 0.32 ± 0.1, and 0.32 ± 0.1, in T2D, IR, and EU, respectively; p<.05). Moreover, T2D patients exhibited worse LV filling dynamics with larger left atrial volume index compared to IR and EU. Right ventricle dysfunction, expressed as a lower TAPSE/PASP ratio, was found in T2D [0.52(0.32-0.72)] than in EU and IR [0.60(0.30-0.90); p<.05]. T2D patients showed a significantly lower VO2 max peak when compared to IR and EU patients (15.8 ± 3.8 vs. 16.5 ± 4.3 vs. 18.4 ± 4.3 ml/Kg/min; p<.003), with an inverse relationship between the HOMAIR classes and VO2 max. Right ventricle structure and function deteriorated more rapidly in T2D, as suggested by more relevant deterioration in TAPSE/PASP ratio (-10% in EU patients, -14% in IR patients, -21% in T2D; p<.05)., Commentary: The study findings suggest that the right ventricle structure, function, and cardiopulmonary performance deteriorate with IR and, more evidently, due to chronic exposure to hyperglycemia in T2D. Impaired exercise tolerance, poor cardiorespiratory fitness, diastolic dysfunction, and left atrial enlargement predispose patients to poor quality of life, suboptimal adherence to physical activity, and an overall increase in the risk of all-cause and cardiovascular mortality. In addition, chronic hyperglycemia accelerates the progression of these alterations, especially in patients with poor glycemic control over time. Highly selective and even more non-selective sodium glucose transporter type 2 inhibitors and glucagon-like peptide 1 receptor agonists should be considered as the first-line therapy for improving CV outcomes in T2D and CHF. Further studies are needed to understand the role of these molecules in treating pre-clinical conditions, such as IR and metabolic syndrome., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Introduction: Atherosclerotic Cardiovascular Diseases (CVD) are among the most relevant causes of morbidity and mortality worldwide, especially in aged people. Statins are one of the leading pharmacological interventions against atherosclerosis and are widely used to reduce the risk of occurring coronary artery diseases and related outcomes in both primary and secondary prevention. The management of chronic diseases is improved considerably over time, leading to an increase in life expectancy despite heavier comorbidity-related burdens in the elderly., Aims: The paper focused on the role of statins in the management of atherosclerosis and related burdens in elderly patients., Results: Statins are essential in reducing the risk of CVD in secondary and primary prevention, particularly in high-risk individuals. Guidelines encourage using specific algorithms with age-specific cutoffs to assess individual cardiovascular risk irrespective of baseline age, as the expansion of life expectancy produces favorable effects of statin treatment in those over 70., Discussion: Besides the estimation of baseline CV risk, a specific age-related assessment is also necessary before prescribing statin treatment in aged people focusing on frailty, potential pharmacological interactions due to polypharmacotherapy, cognitive impairment, and background chronic comorbidities, such as diabetes mellitus. Before starting statin therapy, an accurate choice of type and dose of statins is needed as potential adverse events are more prevalent with high-dose than low-to-moderatedose regimens and with lipophile than hydrophile statins (e.g., potential implication on intra-cerebral cholesterol metabolism)., Conclusion: Despite possible adverse events, elderly patients should receive statins, when appropriate, to avoid the first occurrence of recurrent cardiovascular events and related burdens., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Bone health relies on the equilibrium between resorption and new bone generation. Postmenopausal osteoporosis depends on estrogen deficiency which favorite bone resorption and elevated risk of fractures. Moreover, osteoporosis is characterized by a high release of proinflammatory cytokines suggesting the role of the immune system in the pathogenesis of this complex disease (immunoporosis)., Aims: To review the pathophysiology of osteoporosis from an endocrinological and immunological viewpoint and treatments with a specific focus on nutraceuticals., Methods: PubMed/MEDLINE, Scopus, Google Scholar, and institutional web site were searched. Original articles and reviews were screened and selected by September 2022., Results: The activation of the Gut Microbiota-Bone Axis contributes to bone health by releasing several metabolites, including short-chain fatty acids (SCFAs), that facilitate bone mineralization directly and indirectly by the induction of T regulatory cells, triggering anti-inflammatory pathways., Conclusion: Treatments of postmenopausal osteoporosis are based on lifestyle changes, calcium and vitamin D supplementation, and anti-resorptive and anabolic agents, such as bisphosphonates, Denosumab, Teriparatide, Romosozumab. However, phytoestrogens, polyphenols, probiotics, and polyunsaturated fatty acids may improve bone health by several mechanisms, including anti-inflammatory properties. Specific clinical trials are needed to assess the efficacy/effectiveness of the possible anti-osteoporotic activity of natural products as add on to background treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Evidence shows that a low-grade inflammation sustains type 2 diabetes (T2D). Pancreatic macrophages release cytokines and chemokines that play a fundamental role in the pathophysiology of islet damage and destruction of beta-cells., Methods: The authors discuss the main mechanism by which resident (pancreatic) and circulating macrophages regulate beta-cell development and survival in several scenarios, including T2D, type 1 diabetes mellitus, obesity, and insulin resistance. Data are mostly related to in vitro and animal studies., Results: Lastly, an overview of the role of the Mediterranean diet components (i.e., polyphenols, polyunsaturated fatty acids, prebiotics, probiotics, and vitamins) will be illustrated as potential agents for reducing inflammation and oxidative stress in patients with T2D when used along with antihyperglycemic treatments., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Due to the COVID-19 pandemic, current epidemiological conditions may exacerbate the risk of new-onset, recurrence and relapse of eating disorders. This perspective aims to better analyse the phenomenon., Results: Some data suggest that new-onset and recurrence/relapse of eating disorders are increasing due to the pandemic. Government restrictions, self-confinement, social isolation, restriction to healthcare facilities access, delayed access to diagnosis and cure, fear of contagion, distress and difficulties related to the telemedicine approach contribute to this burden. The Immune system dysfunction usually observed in undernourishment (e.g., anorexia nervosa) could delay the diagnosis of respiratory infections, including COVID-19, and predispose to possible bacterial superinfections. Conversely, patients with binge eating, obesity or metabolic syndrome are susceptible to high-grade systemic inflammation and poor prognosis once the infection has occurred., Discussion: More detailed data combining research on eating disorders and COVID-19 are required despite some evidence. Many data show that telemedicine has beneficial aspects, but its impact on long-term mental health is still poorly understood. Short- and long-term consequences of COVID-19 in patients with eating disorders are unknown, but they will likely become more apparent over time., Conclusion: Working on emotion regulating strategies in a post-pandemic world, when people have inadequate control over the background of negative emotions, could be a future treatment strategy. Long-term studies with a larger sample size are essential to assess the long-term consequences of the blockade on patients and their healthcare providers and identify useful strategies to improve clinical management., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Late-Onset Hypogonadism (LOH) is defined as a clinical and biochemical syndrome associated with advancing age. It is characterized by specific symptoms and less specific manifestations due to deficiency of serum testosterone (T) levels., Objective: This review aims to summarize the evidence related to LOH definition, diagnostic approach, and treatment to answer a clinical question: "Is Testosterone the fountain of youth for aging men?"., Methodology: MEDLINE/PubMed and institutional websites were searched for original papers, guidelines, and position statements published in the last ten years., Results: Observational and randomized controlled studies on T replacement therapy in older men have been reported., Discussion and Conclusion: Despite some heterogeneities regarding diagnostic definition, therapeutic target, and testosterone prescription, all guidelines agreed that male hypogonadism should be diagnosed and managed in aged men as in adulthood. However, trials assessing the efficacy of T therapy conducted for male rejuvenating are lacking; thus, T prescription for this purpose is not recommended., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The Italian population's habits changed dramatically during the "COVID- 19 lockdown" due to physical distancing and self-isolation. Moreover, medical consultations of patients with chronic diseases, such as type 2 diabetes (T2D), were suspended or postponed, unless urgent or semi-urgent, for several consecutive months. Thus, it is expected that the lockdown could have affected glucometabolic control in T2D. v Purpose: The aim of the study was to assess changes in glucometabolic control in a cohort of T2D patients before (T1) and after (T2) the COVID-19 lockdown (March-May 2020)., Methods: The study was approved by the Ethics Committee of the University of Bari, and all patients provided informed written consent to participate. Medical history, complete physical examination, and laboratory assessment were conducted as real-life clinical practice. Changes in clinical and laboratory variables between T1 and T2 were calculated., Results: In detail, 13 patients were on metformin as monotherapy, 36 on GLP-1RA, 12 on sodiumglucose transporter 2 inhibitors (SGLT-2i), and 2 on dipeptidyl-peptidase 4 inhibitors (DPP4i). The mean age was 65.3 years (43-83). Study participants were mainly men (73%). The body weight (BW) ranged from 56 to 145 kg, and the waist circumference ranged from 88 to 146 cm. The mean HbA1c was 51.0 mmol/mol. At T2, no statistically significant changes were observed frombaseline except for BW [-1.6 (-2.60 to -0.62)] and HbA1c [-2.90 (-4.69; -1.12)]., Conclusion: We evaluated the effects of the COVID-19 lockdown on glucometabolic control in patients with background well-controlled T2D. We found that the lockdown had no adverse effects on metabolic profile regardless of background clinical characteristics and antihyperglycemic management. Despite limitations due to the nature of this study (sample size, retrospective observation, lack of data on lifestyle changes in our patients' everyday lives), T2D patients managed in our Diabetes Centers faced the lockdown-related restrictions without any detrimental consequence., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: The prevalence of erectile dysfunction (ED) rises with the number and severity of chronic diseases., Aims: This cross-sectional study assessed the frequency and severity of ED in patients with multiple chronic conditions., Methods: The 5-item International Index of Erectile Function questionnaire (IIEF-5) was used to diagnose and classify ED. The Charlson Comorbidity Index (CCI) was used to assess the burden of chronic comorbidity. The primary outcome was to assess the ED frequency according to CCI severity. The secondary outcomes included the assessment of the correlation between 1) IIEF-5 and total testosterone (TT), 2) CCI and TT, and 3) IIEF-5 and CCI. Lastly, the CCI and modified CCI (mCCI) performances were compared with each other., Results: The overall frequency of ED increased along with the CCI score severity: 45% for CCI=0; 95% for CCI=1; 91% for CCI=2; 99% for CCI≥3 (p<.0001). CCI correlated negatively with TT levels and IIEF-5 score (r=-0.34 and -0.44; p<.0001). Compared to the CCI, a novel proposed mCCI performs well., Discussion: The frequency and severity of ED are relevant in outpatients with sexual complaints and those with chronic comorbidities. Despite limitations, mCCI may be considered a reliable tool to assess the overall burden of multiple chronic conditions in patients with comorbidities., Conclusion: ED is a reliable proxy of overall male health. Further studies are needed to confirm this potential application., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aims: Metformin is the most widely used drug for the first-line treatment of type 2 diabetes mellitus (T2DM), but its use and schedule have been poorly investigated in elderly patients., Methods: We conducted an observational, cross-sectional, multicentric study on metformin in T2DM outpatients older than 65 years who were taking the drug for at least 6 months and referred to Italian Endocrinology and Diabetology Services. The primary endpoint was daily metformin dose, and secondary endpoints were the correlations between metformin dose and age, comorbidities, and concomitant use of other drugs. The study was open to all members of AME (Associazione Medici Endocrinologi)., Results: Fifteen Italian centers recruited 751 consecutive participants (42.9% older than 75 years, 48.6% females). T2DM duration was 12.9 ± 9.7 years (longer than 10 years in 53.8%). Metformin had been used for 10.3 ± 6.8 years (longer than 10 years in 52.4%). Metformin dose was 1.6 ± 0.9 g/day (>1.5 g/day in 63.4%). As compared to the youngest, participants older than 75 years did not differ for metformin daily dose or number of administrations. Metformin dose was significantly directly correlated to eGFR, diabetes duration, and metformin treatment duration., Conclusion: In this real-world study, the minimum daily effective dose of metformin was prescribed in more than half of older T2DM outpatients., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Nonalcoholic fatty liver disease (NAFLD) is commonly observed in patients with type 2 diabetes (T2D). Semaglutide, a glucagon-like peptide 1 receptor agonist, may have a therapeutic role by targeting common mechanisms involved in the pathophysiology of T2D and NAFLD. The study aimed to assess the effectiveness of Semaglutide on NAFLD in patients with T2D., Methods: Forty-eight patients were treated with subcutaneous Semaglutide in add-on to metformin for 52 weeks. After the baseline visit (T0), follow-up was scheduled quarterly (T3, and T6) and then at 12 months of therapy (T12). During each visit, body composition was analyzed by phase-sensitive bio-impedance, and NAFLD was diagnosed and staged by Ultrasound (US) imaging. Surrogate biomarkers of NAFLD were also calculated and followed over time., Results: A significant decrease in anthropometric and glucometabolic parameters, insulin resistance, liver enzymes, and laboratory indices of hepatic steatosis was observed during treatment. Similarly, fat mass and visceral adipose tissue (VAT) decreased over time more than skeletal muscle and free-fat mass. US-assessed VAT thickness and the 12-point steatosis score also declined at T3 up to T12. Liver steatosis improved in most patients (70%), showing a reduction by at least one class in the semiquantitative US staging., Conclusion: Besides glucose control and body composition improvements, Semaglutide was effective in ameliorating the clinical appearance and severity of NAFLD in T2D patients.

Background: Endocrine-disrupting chemicals (EDCs) are natural or synthetic compounds deriving from different human activities and are widely spread into the environment, contributing to indoor and outdoor pollution. EDCs may be conveyed by food and water consumption and skin, airways, placental, and breastfeeding. Upon entering the circulation, they can interfere with endocrine system homeostasis by several mechanisms., Aim: In this narrative review, the authors overviewed the leading mechanisms by which EDCs interact and disrupt the endocrine system, leading to possible human health concerns., Results: The leading mechanisms of EDCs-related toxicity have been illustrated in in vitro studies and animal models and may be summarized as follows: receptor agonism and antagonism; modulation of hormone receptor expression; interference with signal transduction in hormone-responsive cells; epigenetic modifications in hormone-producing or hormone-responsive cells; interference with hormone synthesis; interference with hormone transport across cell membranes; interference with hormone metabolism or clearance; interference with the destiny of hormone-producing or hormone- responsive cells., Discussion: Despite these well-defined mechanisms, some limitations do not allow for conclusive assumptions. Indeed, epidemiological and ecological studies are currently lacking and usually refer to a specific cluster of patients (occupational exposure). Methodological aspects could further complicate the issue since these studies could require a long time to provide useful information. The lack of a real unexposed group in environmental conditions, possible interference of EDCs mixture on biological results, and unpredictable dose-response curves for some EDCs should also be considered significant limitations., Conclusion: Given these limitations, specific observational and long-term studies are needed to identify at-risk populations for adequate treatment of exposed patients and effective prevention plans against excessive exposure to EDCs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Endocrine Disrupting Chemicals (EDCs) are ubiquitous and may significantly contribute to environmental pollution and contamination in humans and wildlife. Ecological pollutants could interfere with bone homeostasis through different mechanisms, including hormonal imbalance, direct osteoblast toxicity, and enhancement of osteoclasts activity, leading to either osteopenia or osteoporosis. Among these chemicals, bisphenols, dioxins, polycyclic aromatic hydrocarbons, polychlorobiphenyls, poly- and perfluoroalkyl, phthalates, parabens, organotins, and cadmium may play a role in the bone disruption., Methods: Authors searched PubMed/MEDLINE, ISI-web of knowledge, and Google scholar databases for medical subject headings terms and free-text words related to the classes mentioned above of chemicals and bone metabolism and remodeling for better clarifying and understanding the main mechanisms of bone disruption., Results: Several EDCs act as xeno-estrogens. Considering that estrogens play a significant role in regulating bone remodeling, most of these chemicals generate hormonal imbalance with possible detrimental consequences on bone tissue structure and its mechanical and non-mechanical properties., Discussion: Much evidence about bone disruptors was obtained from in vitro studies or animal models with equivocal results. Besides, a few data have been acquired from humans, and most of these data focused on the impact of EDCs on bone mineral density without considering their influence on long-term fracture risk. Moreover, humans may be exposed to a mixture of EDCs, and the final effect on bone metabolism might be attributable to either synergistic or antagonist effects. Age of first exposure, cumulative exposure over time, and the usually observed non-monotonic dose-response curve for EDCs should be considered as other essential variables influencing bone metabolism's final effect., Conclusion: Given these variables, observational studies are needed to analyze this issue for ecological purposes better and preserve bone health., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Foam cells, mainly derived from monocytes-macrophages, contain lipid droplets essentially composed of cholesterol in their cytoplasm. They infiltrate the intima of arteries, contributing to the formation of atherosclerotic plaques., Pathogenesis: Foam cells damage the arterial cell wall via the release of proinflammatory cytokines, free radicals, and matrix metalloproteinases, enhancing the plaque size up to its rupture., Therapy: A correct dietary regimen seems to be the most appropriate therapeutic approach to minimize obesity, which is associated with the formation of foam cells. At the same time, different types of antioxidants have been evaluated to arrest the formation of foam cells, even if the results are still contradictory. In any case, a combination of antioxidants seems to be more efficient in the prevention of atherosclerosis., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Body weight (BW) loss is an essential therapeutic goal in type 2 diabetes (T2D). Glucagon-like peptide-1 receptor agonists are effective in reducing BW, but their effect on body composition has not yet been fully explored. The study aim was to assess the impact of Semaglutide on body composition in patients with T2D., Methods: Forty patients with T2D were treated with subcutaneous Semaglutide and evaluated at the baseline (T0) and after three (T3) and six (T6) months. Body composition was assessed by a phase-sensitive bioimpedance analyzer. Visceral adipose tissue (VAT) thickness was also measured with an ultrasonographic method (US-VAT). Anthropometric variables, muscular strength, and laboratory tests were analyzed and compared., Results: A significant decrease in VAT, the fat mass index (FMI), and BW loss was observed at all observation times. US-VAT, the skeletal mass index (SMI), the fat-free mass index (FFMI), waist circumferences, and glycated hemoglobin had lessened after three months and remained stable at T6. No variations in muscle strength, the muscle quality index, and body water were found., Discussion: In a real-life setting, Semaglutide provided significant weight loss mainly due to a reduction in the FMI and VAT, with non-clinically relevant changes in the SMI, the FFMI, and muscle strength. Most importantly, the results were obtained after three months of treatment and persisted thereafter.

Introduction: There is scientific consistency in the concept of ultra-processed foods (UPFs) as a descriptor of an unhealthy diet. The most recent literature points to troubling evidence that policies adopted to address the SARS-CoV-2 pandemic may have contributed to diverting eating habits toward a poorer diet. Considering the historically unique SARS-CoV-2 pandemic lockdown scenario, and the health burden imposed by UPFs on human health, it is critical to investigate how the epidemic has influenced UPF intake directly. Reviewing the literature, we aimed to assess the changes in the consumption of UPFs during the pandemic lockdown compared to previous habits in the general population. Methods: Consulting six databases, we examined articles investigating the consumption of UPFs according to the NOVA classification both before the SARS-CoV-2 pandemic and during lockdowns. In total, 28 reports were included in the final analysis. Results: A clear trend of an increasing consumption of sweets (chocolate, candy, cookies, pastries, cakes, desserts, and confectionery, 31.75% increase vs. 21.06% decrease), packaged fatty or salty snacks (23.71% increase vs. 20.73% decrease), and baked goods (bread products, pizza, and sandwiches, 28.03% increase vs. 13.5% decrease) emerged, versus a decrease in ready-to-eat dishes (16.2% increase vs. 22.62% decrease) and ready-made meals (10.6% increase vs. 31.43% decrease), such as instant soups, canned foods, fast food, and chips, as well as sugary drinks in general (14.55% increase vs. 22.65% decrease). No trend was observed for processed meat consumption. Conclusion: The current pandemic scenario raises concerns about the increased consumption of UPFs, especially sweets, snacks, and baked goods, and points to an urgent need to implement policy strategies to manage the trade in these foods from a preventive perspective.

Chronic heart failure (CHF) leads to an excess of urgent ambulatory visits, recurrent hospital admissions, morbidity, and mortality regardless of medical and non-medical management of the disease. This excess of risk may be attributable, at least in part, to comorbid conditions influencing the development and progression of CHF. In this perspective, the authors examined and described the most common endocrine disorders observed in patients with CHF, particularly in individuals with reduced ejection fraction, aiming to qualify the risks, quantify the epidemiological burden and discuss about the potential role of endocrine treatment. Thyroid dysfunction is commonly observed in patients with CHF, and sometimes it could be the consequence of certain medications (e.g., amiodarone). Male and female hypogonadism may also coexist in this clinical context, contributing to deteriorating the prognosis of these patients. Furthermore, growth hormone deficiency may affect the development of adult myocardium and predispose to CHF. Limited recommendation suggests to screen endocrine disorders in CHF patients, but it could be interesting to evaluate possible endocrine dysfunction in this setting, especially when a high suspicion coexists. Data referring to long-term safety and effectiveness of endocrine treatments in patients with CHF are limited, and their impact on several "hard" endpoints (such as hospital admission, all-cause, and cardiovascular mortality) are still poorly understood., (© 2021. The Author(s).)

Obesity is a growing pandemic. Endocrine-disrupting chemicals are widespread in the environment. In this perspective, the authors examine the issue related to the exposure to several chemicals with endocrine-disrupting properties as promoting factors to obesity. Data show that Phthalates, Bisphenol compounds, Persistent Organic Pollutants (POPs), solvents, and personal care products can modify metabolic properties in a dose-response and sex-specific manner. Phthalates and bisphenol compounds increase body mass index, waist circumference, waist to height ratio, and the sum of skinfold thicknesses in women and not in men. Low-dose exposure to Persistent Organic Pollutants is strongly associated with increased body mass index in men and decreased this parameter in women. The mechanism through which these compounds act on anthropometric parameters is not entirely understood. Several studies suggest a possible interference in gonadotropin secretion and the thyroid axis. These inspire a decrease in both total and free testosterone levels in men and FT3 and FT4 levels in women, particularly after a pregnancy. The impact of endocrine disruptor chemicals on adipose tissue inflammation and future cardio-metabolic disorders remains to be elucidated. Therefore, studies involving both healthy and obese individuals are needed to unambiguously confirm results from in vitro and animal models., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A wealth of information suggests that hyperglycemia plays a paramount role in diabetes- related chronic complications. Notably, in Type 2 Diabetes Mellitus (T2DM), a persistent condition of hyperglycemia and altered insulin signaling seems to account for a status of chronic low-grade inflammation. This systemic inflammatory condition, in turn, depends on the profound impairment of the immune machinery, especially in some corporeal districts such as the adipose tissue, pancreatic islets, endothelia, and circulating leukocytes. Interestingly, poor glycemic control has been associated with cardiac autoimmunity in patients with Type 1 Diabetes (T1DM), and cardiac autoantibody positivity is associated with an increased risk of Cardiovascular Diseases (CVD) decades later. This condition also suggests a role for autoimmune mechanisms in CVD development in patients with T1DM, possibly through inflammatory pathways. Evidence has been provided for an elevated release of cytokines, such as interleukin (IL)-1 beta and IL-6, as well as chemokines (C-C motif Ligand 2 and IL-8). Of note, these mediators are responsible for abnormal leukocyte trafficking into many tissues, contributing to insulin resistance, reduced insulin secretion, and vascular complications. In fact, hyperglycemia in individuals with diabetes mellitus is associated with higher circulating E-selectin, soluble Cell Adhesion Molecule (sCAM)-1, and vascular CAM-1 compared to normoglycemic healthy volunteers. Therefore, patients with diabetes mellitus exhibit an exaggerated adhesion of leukocytes to endothelia, and this phenomenon is related to hyperglycemia. The increased production of advanced glycosylation end products or AGEs activates a further cascade of noxious events with a massive generation of Reactive Oxygen Radicals (ROS) and enhanced expression of CAMs., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)