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Pleural mesothelioma (PM) is a tumor related to adverse prognosis. The PM WHO classification has mainly identified three major subtypes of PM which are epithelioid, biphasic, and sarcomatoid. Sarcopenia is a medical issue related to a reduction in muscle mass and strength. It represents a major health issue globally because it is related to adverse effects such as hospitalization, increased length of stay, disability, increased morbidity and mortality and augmented health care expenditures. In this literature review, we attempted to examine the upcoming association between sarcopenia and PM. As recorded by the current literature, muscle loss in PM subjects was related to poorer survival and lower levels of activity. Subjects with PM had increased rates of pre-sarcopenia and malnutrition, while pre-sarcopenia was related to worse activity levels, and malnutrition was related to worse quality of life (QoL). Both tumor volume and sarcopenia were related to long-term mortality in surgically treated PM subjects, while sarcopenia was present both pre-operatively and post-operatively in these subjects. In addition, post-operative sarcopenic subjects showed a decreased 3-year overall survival (OS) in comparison with those who did not have sarcopenia, while pre-operative sarcopenia was importantly related to an increased rate of post-operative adverse outcomes. More studies are needed to validate these claims.

Ischemic stroke (IS) exhibits significant heterogeneity in terms of etiology and pathophysiology. Several recent studies highlight the significance of inflammation in the onset and progression of IS. White blood cell subtypes, such as neutrophils and monocytes, participate in the inflammatory response in various ways. On the other hand, high-density lipoproteins (HDL) exhibit substantial anti-inflammatory and antioxidant actions. Consequently, novel inflammatory blood biomarkers have emerged, such as neutrophil to HDL ratio (NHR) and monocyte to HDL ratio (MHR). Literature research of two databases (MEDLINE and Scopus) was conducted to identify all relevant studies published between 1 January 2012 and 30 November 2022 dealing with NHR and MHR as biomarkers for IS prognosis. Only full-text articles published in the English language were included. Thirteen articles have been traced and are included in the present review. Our findings highlight the utility of NHR and MHR as novel stroke prognostic biomarkers, the widespread application, and the calculation of which, along with their inexpensive cost, make their clinical application extremely promising.

Circulating cell-free DNA (ccfDNA) of mitochondrial origin (ccf-mtDNA) consists of a minor fraction of total ccfDNA in blood or in other biological fluids. Aberrant levels of ccf-mtDNA have been observed in many pathologies. Here, we introduce a simple and effective standardized Taqman probe-based dual-qPCR assay for the simultaneous detection and relative quantification of nuclear and mitochondrial fragments of ccfDNA. Three pathologies of major burden, one malignancy (Breast Cancer, BrCa), one inflammatory (Osteoarthritis, OA) and one metabolic (Type 2 Diabetes, T2D), were studied. Higher levels of ccf-mtDNA were detected both in BrCa and T2D in relation to health, but not in OA. In BrCa, hormonal receptor status was associated with ccf-mtDNA levels. Machine learning analysis of ccf-mtDNA datasets was used to build biosignatures of clinical relevance. (A) a three-feature biosignature discriminating between health and BrCa (AUC: 0.887) and a five-feature biosignature for predicting the overall survival of BrCa patients (Concordance Index: 0.756). (B) a five-feature biosignature stratifying among T2D, prediabetes and health (AUC: 0.772); a five-feature biosignature discriminating between T2D and health (AUC: 0.797); and a four-feature biosignature identifying prediabetes from health (AUC: 0.795). (C) a biosignature including total plasma ccfDNA with very high performance in discriminating OA from health (AUC: 0.934). Aberrant ccf-mtDNA levels could have diagnostic/prognostic potential in BrCa and Diabetes, while the developed multiparameter biosignatures can add value to their clinical management.

Evidence from large epidemiological studies has shown that obesity may predispose to increased Th2 inflammation and increase the odds of developing asthma. On the other hand, there is growing evidence suggesting that metabolic dysregulation that occurs with obesity, and more specifically hyperglycemia and insulin resistance, may modify immune cell function and in some degree systemic inflammation. Insulin resistance seldom occurs on its own, and in most cases constitutes a clinical component of metabolic syndrome, along with central obesity and dyslipidemia. Despite that, in some cases, hyperinsulinemia associated with insulin resistance has proven to be a stronger risk factor than body mass in developing asthma. This finding has been supported by recent experimental studies showing that insulin resistance may contribute to airway remodeling, promotion of airway smooth muscle (ASM) contractility and proliferation, increase of airway hyper-responsiveness and release of pro-inflammatory mediators from adipose tissue. All these effects indicate the potential impact of hyperinsulinemia on airway structure and function, suggesting the presence of a specific asthma phenotype with insulin resistance. Epidemiologic studies have found that individuals with severe and uncontrolled asthma have a higher prevalence of glycemic dysfunction, whereas longitudinal studies have linked glycemic dysfunction to an increased risk of asthma exacerbations. Since the components of metabolic syndrome interact with one another so much, it is challenging to identify each one’s specific role in asthma. This is why, over the last decade, additional studies have been conducted to determine whether treatment of type 2 diabetes mellitus affects comorbid asthma as shown by the incidence of asthma, asthma control and asthma-related exacerbations. The purpose of this review is to present the mechanism of action, and existing preclinical and clinical data, regarding the effect of insulin resistance in asthma.

Abstract Objective to assess the effects of cilostazol on pain-free walking distance in PAD patients with IC at 3 and 6 months in a real world, prospective, observational study. We included 1015 PAD patients presenting with IC (71.3% men, 93.5% white, mean age 69.2 ± 8.7 years). Patients were followed up for 6 months by their physicians. Results Cilostazol significantly increased pain-free walking distance by a median of 285 and 387 m at 3 and 6 months, respectively (p

Abstract Background Diabetic kidney disease (DKD), the most common cause of kidney failure and end-stage kidney disease worldwide, will develop in almost half of all people with type 2 diabetes. With the incidence of type 2 diabetes continuing to increase, early detection and management of DKD is of great clinical importance. Main body This review provides a comprehensive clinical update for DKD in people with type 2 diabetes, with a special focus on new treatment modalities. The traditional strategies for prevention and treatment of DKD, i.e., glycemic control and blood pressure management, have only modest effects on minimizing glomerular filtration rate decline or progression to end-stage kidney disease. While cardiovascular outcome trials of SGLT-2i show a positive effect of SGLT-2i on several kidney disease-related endpoints, the effect of GLP-1 RA on kidney-disease endpoints other than reduced albuminuria remain to be established. Non-steroidal mineralocorticoid receptor antagonists also evoke cardiovascular and kidney protective effects. Conclusion With these new agents and the promise of additional agents under clinical development, clinicians will be more able to personalize treatment of DKD in patients with type 2 diabetes.

Abstract Background Osteoprotegerin (OPG) and osteopontin (OPN) are vascular calcification inhibitors with a known role in the atherosclerotic and inflammatory process. We investigated their relationship with adverse outcomes (restenosis/adverse cardiovascular events) after endovascular revascularisation of patients with peripheral arterial disease (PAD). Methods 203 consecutive patients were enrolled in the PAD group (PADG) and 78 age and sex-matched subjects with less than two cardiovascular risk factors served as control group (COG). PADG underwent standard medical assessment at baseline and 12 months after the procedure. During follow up major adverse cardiovascular events (MACEs) including arterial restenosis with need for reintervention were documented and the PADG was divided accordingly into two subgroups. Results During 12-month follow-up, 82 MACE were recorded (MACE subgroup). The rest of 124 PAD patients remained free of MACE (non-MACE subgroup). At baseline, OPG (9.89 ± 2.85 ng/ml vs 3.47 ± 1.95 ng/ml, p

The past two decades have witnessed telemedicine becoming a crucial part of health care as a method to facilitate doctor-patient interaction. Due to technological developments and the incremental acquisition of experience in its use, telemedicine’s advantages and cost-effectiveness has led to it being recognised as specifically relevant to diabetology. However, the pandemic created new challenges for healthcare systems and the rate of development of digital services started to grow exponentially. It was soon discovered that COVID-19-infected patients with diabetes had an increased risk of both mortality and debilitating sequelae. In addition, it was observed that this higher risk could be attenuated primarily by maintaining optimal control of the patient’s glucose metabolism. As opportunities for actual physical doctor-patient visits became restricted, telemedicine provided the most convenient opportunity to communicate with patients and maintain delivery of care. The wide range of experiences of health care provision during the pandemic has led to the development of several excellent strategies regarding the applicability of telemedicine across the whole spectrum of diabetes care. The continuation of these strategies is likely to benefit clinical practice even after the pandemic crisis is over.

Abstract Background RBP4 is an adipokine with an established role in atherosclerosis, while adiponectin has unique anti-inflammatory properties. We investigated the association of RBP4 and adiponectin with the presence of symptomatic peripheral artery disease (PAD) and their possible prognostic role in major adverse cardiovascular events (MACE). Methods We enrolled 168 consecutive patients with symptomatic, established PAD, requiring revascularization by endovascular means of any or both of their lower limbs. 88 age- and sex-matched subjects with less than 2 classical cardiovascular risk factors served as controls. Clinical parameters, glycemic and lipid profile, RBP4 and adiponectin levels were assayed. The occurrence of MACE was recorded during the 6-month follow-up and patients were assigned to MACE and non-MACE subgroups. Results The presence of symptomatic PAD was significantly correlated with age, diabetes, hsCRP, RBP4 and low adiponectin levels (p

Abstract Diabetic sensorimotor polyneuropathy (DSPN) is encountered in approximately one‐third of people with diabetes. This, in turn, might markedly impoverish their quality of life, mainly owing to neuropathic pain and foot ulcerations. Painful DSPN might be as frequent as 25% in diabetes patients. Symptoms as a result of DSPN typically comprise pain, paresthesia and numbness in the distal lower limbs. Asymptomatic DSPN might reach 50% among patients with this condition. Unfortunately, DSPN is still not adequately diagnosed and treated. Its management has three priorities: (i) lifestyle improvement, near‐normoglycemia and multifactorial cardiovascular risk intervention; (ii) pathogenesis‐oriented pharmacotherapy; and (iii) symptomatic alleviation of pain. Intensive diabetes therapy showed evidence for favorable effects on the incidence and deterioration of DSPN in type 1 diabetes, but not type 2 diabetes. Among pathogenesis‐oriented treatments, α‐lipoic acid, actovegin, benfotiamine and epalrestat are currently authorized to treat DSPN in several countries. Symptomatic therapy uses analgesics, notably antidepressants, opioids and anticonvulsants, reducing pain by ≥50% in approximately 50% of individuals, but might be limited, particularly by central nervous system‐related adverse events. Local treatment with the capsaicin 8% patch might offer an alternative. In addition to pain relief, therapy should improve sleep, mobility and quality of life. In conclusion, multimodal treatment of DSPN should consider the individual risk profile, pathogenetic treatment and pain management using pharmacotherapy (combinations, if required), as well as non‐pharmacological options.

Abstract Advanced glycation end-products (AGEs) are heterogeneous molecules produced by the non-enzymatic glycation of proteins, lipids, or nucleic acids during hyperglycaemia. Accumulation of AGEs in the peripheral nerves has recently been proposed as an additional risk factor for the development of diabetic neuropathy (DN). The gold standard for measurement of tissue-bound AGEs is tissue biopsy. However, their assessment with the newer, fast and simple method of skin autofluorescence (sAF) has recently gained special interest by virtue of its non-invasive, highly reproducible nature and its acceptable correlation with the reference method of skin biopsy. Accumulation of tissue AGEs evaluated by sAF has been shown to independently correlate with DN. Importantly, increasing evidence underscores their potential value as early biomarkers of the latter. Further important associations include diabetic nephropathy, diabetic retinopathy and cardiovascular autonomic neuropathy. However, the value of the implementation of screening with skin AGEs for DN remains unclear. The aim of the present review is to critically summarise current evidence on the association between skin AGEs and diabetic microvascular complications, with a particular emphasis on diabetic neuropathy, and to note the most important limitations of existing knowledge. Longer follow-up studies are also highly anticipated to clarify its role and provide data on patient selection and cost-effectiveness.

Diabetic nephropathy (DN) is the leading cause of end-stage renal disease (ESRD) worldwide. Its pathogenesis encompasses functional alterations involving elevated intraglomerular and systemic pressure, increased activity of the renin-angiotensin system (RAS) and oxidative stress, and the eventual development of renal fibrosis. The management of DN involves the optimization of blood pressure (BP) and blood glucose targets. However, treatment of these risk factors slows down but does not stop the progression of DN. Innovative pharmacologic therapies for dyslipidemia and type 2 diabetes mellitus (T2DM) could play a key role in bridging this gap and attenuating the residual risk of DN beyond traditional risk factor management. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sodium-glucose cotransporter-2 inhibitors (SGLT-2is), and inhibitors of mineralocorticoid receptor-mediated sodium reabsorption are recently introduced drug classes that have been shown to have positive effects on kidney function in individuals with T2DM. The aim of this review is to provide an update on the therapeutic options available in order to prevent or slow the onset and progression of DN in diabetic patients.

Major cardiovascular (CV) outcome trials with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are currently available. These agonists have proven their CV safety, in harmony with the US Food and Drug Administration (FDA) recommendation for antidiabetic drugs. The potential cardioprotective effect of incretin-based therapies is attributed to their multiple non-glycaemic actions in the CV system, including changes in insulin resistance, weight loss, reduction in blood pressure, improved lipid profile and direct effects on the heart and vascular endothelium. Liraglutide, semaglutide and albiglutide have been demonstrated to reduce the risk of major adverse cardiac events (MACE), whereas lixisenatide and extended-release exenatide had a neutral effect. Thus, it is conceivable that there are different drug-specific properties across the class of GLP-1 RAs. In this review, we discuss the results of the five recently published randomised CV outcome trials with GLP-1 RAs, along with the potential differences and the pleiotropic actions of these agents on the CV system. Keywords: Cardiovascular disease, Diabetes mellitus, Randomised controlled trials, Treatment

Efforts in the fight against COVID-19 are achieving success in many parts of the world, although progress remains slow in other regions. We believe that a syndemic approach needs to be adopted to address this pandemic given the strong apparent interplay between COVID-19, its related complications, and the socio-structural environment. We have assembled an international, multidisciplinary group of researchers and clinical practitioners to promote a novel syndemic approach to COVID-19: the CArdiometabolic Panel of International experts on Syndemic COvid-19 (CAPISCO). This geographically diverse group aims to facilitate collaborative-networking and scientific exchanges between researchers and clinicians facing a multitude of challenges on different continents during the pandemic. In the present article we present our “manifesto”, with the intent to provide evidence-based guidance to the global medical and scientific community for better management of patients both during and after the current pandemic.

Periodontitis is a microbially driven, host-mediated disease that leads to loss of periodontal attachment and resorption of bone. It is associated with the elevation of systemic inflammatory markers and with the presence of systemic comorbidities. Coronavirus disease 2019 (COVID-19) is a contagious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the majority of patients have mild symptoms, others experience important complications that can lead to death. After the spread of the COVID-19 pandemic, several investigations demonstrating the possible relationship between periodontitis and COVID-19 have been reported. In addition, both periodontal disease and COVID-19 seem to provoke and/or impair several cardiometabolic complications such as cardiovascular disease, type 2 diabetes, metabolic syndrome, dyslipidemia, insulin resistance, obesity, non-alcoholic fatty liver disease, and neurological and neuropsychiatric complications. Therefore, due to the increasing number of investigations focusing on the periodontitis-COVID-19 relationship and considering the severe complications that such an association might cause, this review aims to summarize all existing emerging evidence regarding the link between the periodontitis-COVID-19 axis and consequent cardiometabolic impairments.

Guidelines have increasingly stressed the concept that adequate glycemic control is required to prevent or decrease the macro- and microvascular complications of type 2 diabetes mellitus (T2DM). PPAR-gamma agonists (“glitazones”) are no longer prioritized due to their effects on heart failure. However, the association between these drugs and innovative therapies could be a valuable tool to attenuate the risk factors of the metabolic syndrome. Glitazones are used for the treatment of diabetes and associated comorbidities. There is substantial scientific evidence demonstrating the effect of glitazones at a cardiometabolic level, as well as on hematological and neurological pathologies that point to their usefulness. The use of glitazones has always been controversial both for the type of patients who must take these drugs and for the side effects associated with them. Unfortunately, the recent guidelines do not include them among the preferred drugs for the treatment of hyperglycemia and rosiglitazone is out of the market in many countries due to an adverse cardiovascular risk profile. Even though real-life studies have proven otherwise, and their pleiotropic effects have been highlighted, they have been unable to achieve primacy in the choice of antihyperglycemic drugs. It would be appropriate to demonstrate the usefulness of pioglitazone and its therapeutic benefit with further cardiovascular safety studies.

Coronavirus disease 2019 (COVID-19) is a highly heterogeneous disease regarding severity, vulnerability to infection due to comorbidities, and treatment approaches. The hypothalamic–pituitary–adrenal (HPA) axis has been identified as one of the most critical endocrine targets of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that might significantly impact outcomes after infection. Herein we review the rationale for glucocorticoid use in the setting of COVID-19 and emphasize the need to have a low index of suspicion for glucocorticoid-induced adrenal insufficiency, adjusting for the glucocorticoid formulation used, dose, treatment duration, and underlying health problems. We also address several additional mechanisms that may cause HPA axis dysfunction, including critical illness-related corticosteroid insufficiency, the direct cytopathic impacts of SARS-CoV-2 infection on the adrenals, pituitary, and hypothalamus, immune-mediated inflammations, small vessel vasculitis, microthrombotic events, the resistance of cortisol receptors, and impaired post-receptor signaling, as well as the dissociation of ACTH and cortisol regulation. We also discuss the increased risk of infection and more severe illness in COVID-19 patients with pre-existing disorders of the HPA axis, from insufficiency to excess. These insights into the complex regulation of the HPA axis reveal how well the body performs in its adaptive survival mechanism during a severe infection, such as SARS-CoV-2, and how many parameters might disbalance the outcomes of this adaptation.

Aim of the Study. To examine the correlation between skin AGEs and parameters of distal sensorimotor polyneuropathy (DSPN) in type 2 diabetes mellitus (T2DM). Materials and Methods. We included 132 subjects (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm. The device enables single and automated triplicate measurements: both of these were performed. DSPN was diagnosed through the neuropathy disability score (NDS). Small nerve fibre function was assessed by temperature and pinprick sensation on the foot. Bilateral measurement of the vibration perception threshold (VPT) on the hallux was carried out by using a neurothesiometer (Horwell Scientific Laboratory Supplies). Results. Single and triplicate AGE measurements were positively correlated with each other (Pearson’s correlation coefficient r=0.991, 95%CI=0.987-0.994, p

Background Type 2 diabetes mellitus is a risk factor for lower extremity arterial disease. Cilostazol expresses antiplatelet, anti‐inflammatory, and vasodilator actions and improves the claudication intermittent symptoms. We investigated the efficacy and safety of adjunctive cilostazol to clopidogrel‐treated patients with type 2 diabetes mellitus exhibiting symptomatic lower extremity arterial disease, in the prevention of ischemic vascular events and improvement of the claudication intermittent symptoms. Methods and Results In a prospective 2‐arm, multicenter, open‐label, phase 4 trial, patients with type 2 diabetes mellitus with intermittent claudication receiving clopidogrel (75 mg/d) for at least 6 months, were randomly assigned in a 1:1 ratio, either to continue to clopidogrel monotherapy, without receiving placebo cilostazol (391 patients), or to additionally receive cilostazol, 100 mg twice/day (403 patients). The median duration of follow‐up was 27 months. The primary efficacy end point, the composite of acute ischemic stroke/transient ischemic attack, acute myocardial infarction, and death from vascular causes, was significantly reduced in patients receiving adjunctive cilostazol compared with the clopidogrel monotherapy group (sex‐adjusted hazard ratio [HR], 0.468; 95% CI, 0.252–0.870; P=0.016). Adjunctive cilostazol also significantly reduced the stroke/transient ischemic attack events (sex‐adjusted HR, 0.38; 95% CI, 0.15–0.98; P=0.046) and improved the ankle‐brachial index and pain‐free walking distance values (P=0.001 for both comparisons). No significant difference in the bleeding events, as defined by Bleeding Academic Research Consortium criteria, was found between the 2 groups (sex‐adjusted HR, 1.080; 95% CI, 0.579–2.015; P=0.809). Conclusions Adjunctive cilostazol to clopidogrel‐treated patients with type 2 diabetes mellitus with symptomatic lower extremity arterial disease may lower the risk of ischemic events and improve intermittent claudication symptoms, without increasing the bleeding risk, compared with clopidogrel monotherapy. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02983214.

Research Question: Previous cross-sectional studies have shown an association between sudomotor dysfunction and diabetic foot ulceration (DFU). The aim of this prospective multicenter study was to determine the role of dryness of foot skin and of established neurological modalities in the prediction of risk for foot ulceration in a cohort of individuals with diabetes mellitus (DM).Design: The study was conducted from 2012 to 2017. A total of 308 subjects with DM without history of DFU or critical limb ischemia completed the study. Diabetic neuropathy was assessed using the neuropathy symptom score (NSS) and neuropathy disability score (NDS). In a subset of participants, vibration perception threshold (VPT) was evaluated. Dryness of foot skin was assessed by the visual indicator plaster method (IPM). The diagnostic performance of the above neurological modalities for prediction of DFU was tested by receiver operating characteristic curve (ROC) analysis.Results: During the 6-year follow-up, 55 patients (annual ulceration incidence 2.97%) developed DFU. Multivariate Cox-regression analysis after controlling for the effect of age, gender, and DM duration demonstrated that the risk (hazard ratio, 95% confidence intervals) of DFU increased significantly with either abnormal IPM (3.319, 1.460–7.545, p = 0.004) or high (≥6) NDS (2.782, 1.546–5.007, p = 0.001) or high (≥25 volts) VPT (2.587, 1.277–5.242, p = 0.008). ROC analysis showed that all neurological modalities could discriminate participants who developed DFU (p < 0.001). IPM testing showed high sensitivity (0.86) and low specificity (0.49), while high vs. low NDS and VPT showed low sensitivity (0.40 and 0.39, respectively) and high specificity (0.87 and 0.89, respectively) for identification of patients at risk for DFU.Conclusion: Dryness of foot skin assessed by the IPM predicts the development of DFU. IPM testing has high sensitivity, whereas high NDS and VPT have high specificity in identifying subjects at risk for DFU. The IPM can be included in the screening methods for identification of the foot at risk.

The current management of Type 2 Diabetes Mellitus (T2DM) includes incretin-based treatments able to enhance insulin secretion and peripheral insulin sensitivity as well as improve body mass, inflammation, plasma lipids, blood pressure, and cardiovascular outcomes. Dietary Free Fatty Acids (FFA) regulate metabolic and anti-inflammatory processes through their action on incretins. Selective synthetic ligands for FFA1-4 receptors have been developed as potential treatments for T2DM. To comprehensively review the available evidence for the potential role of FFA receptor agonists in the treatment of T2DM, we performed an electronic database search assessing the association between FFAs, T2DM, inflammation, and incretins. Evidence indicates that FFA1-4 agonism increases insulin sensitivity, induces body mass loss, reduces inflammation, and has beneficial metabolic effects. There is a strong inter-relationship between FFAs and incretins. FFA receptor agonism represents a potential target for the treatment of T2DM and may provide an avenue for the management of cardiometabolic risk in susceptible individuals. Further research promises to shed more light on this emerging topic.

There is increasing presence of fructose in food and drinks, and some evidence suggests that its higher consumption increases cardiovascular risk, although the mechanisms still remain not fully elucidated. Cardiovascular diseases (CVD) are still responsible for one-third of deaths worldwide, and therefore, their prevention should be assessed and managed comprehensively and not by the evaluation of individual risk factor components. Lifestyle risk factors for CVD include low degree of physical activity, high body mass index, alcohol consumption, smoking, and nutritional factors. Indeed, nutritional risk factors for CVD include unhealthy dietary behaviors, such as high intake of refined foods, unhealthy fats, added sugars, and sodium and a low intake of fruits, vegetables, whole grains, fiber, fish, and nuts. Even though there is no definitive association between CVD incidence and high consumption of total sugar, such as sucrose and fructose, there is, however, evidence that total sugars, added sugars, and fructose are harmfully associated with CVD mortality. Since high fructose intake is associated with elevated plasma triglyceride levels, as well as insulin resistance, diabetes hyperuricemia, and non-alcoholic fatty liver disease, further longitudinal studies should be conducted to fully elucidate the potential association between certain sugars and CVD.

Obstructive sleep apnoea syndrome (OSAS) is a common disorder of multifactorial pathogenesis and is associated with obesity, diabetes and cardiovascular disease. Vitamin D is a fat-soluble vitamin with an important function in calcium absorption and homeostasis, which is also implicated in several nonskeletal conditions. The prevalence of vitamin D deficiency is increasing worldwide and is associated with similar metabolic disturbances to OSAS. Moreover, recent data suggest that in OSAS patients serum levels of vitamin D are lower compared with non-apnoeic subjects. However, the mechanisms linking vitamin D deficiency and OSAS are not completely understood and several hypotheses have been advanced. To date, a limited number of studies have assessed the association between lower serum concentrations of vitamin D and OSAS, and have reported inconsistent results. Similarly, contradictory results have been produced by studies which evaluated the effect of continuous positive airway pressure treatment on serum vitamin D levels. The aim of this review is to summarise current knowledge on the association between OSAS and vitamin D levels. Key points Vitamin D insufficiency prevalence is increasing worldwide and presents with similar comorbidities and risk factors to OSAS. The nonskeletal actions of vitamin D may contribute to the development of OSAS through immune system modulation, myopathy and inflammation. Studies evaluating serum vitamin D concentrations in OSAS patients and the effect of CPAP treatment report contradictory results, often influenced by confounding factors, such as obesity. There appears to be potential for use of vitamin D supplementation in OSAS patients as a means of reducing the incidence of cardiovascular disease, a comorbidity common in both conditions. Educational aims To assess the potential association between OSAS and serum levels of vitamin D. To discuss the pathogenetic mechanisms linking OSAS and vitamin D insufficiency. To illustrate the effect of CPAP treatment on vitamin D concentration in OSAS patients.

Chronic obstructive pulmonary disease (COPD) is a common disorder with an increasing prevalence, characterised by persistent respiratory symptoms and airflow limitation. Systemic inflammation is involved in the pathogenesis of COPD and can also predispose to metabolic disorders (e.g., metabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD)). Such comorbidities can negatively affect COPD outcomes, cardiovascular risk, and quality of life. Apart from NAFLD, abnormal peri-organ or intra-organ fat (APIFat) could be considered as markers for cardiometabolic diseases and even for COPD. The present narrative review considers the associations of COPD with MetS, NAFLD, and other APIFat, including epicardial, perirenal, peripancreatic, and intramuscular adipose tissue. Further research is needed to define these relationships and identify any potential clinical implications.

Background and Objectives: Distal symmetrical polyneuropathy (DSPN) is one of the most common chronic complications of diabetes mellitus. Although it is usually characterized by progressive sensory loss, some patients may develop chronic pain. Assessment of DSPN is not difficult, but the biggest challenge is making the correct diagnosis and choosing the right treatment. The treatment of DSPN has three primary objectives: glycemic control, pathogenic mechanisms, and pain management. The aim of this brief narrative review is to summarize the current pharmacological treatment of painful DSPN. It also summarizes knowledge on pathogenesis-oriented therapy, which is generally overlooked in many publications and guidelines. Materials and Methods: The present review reports the relevant information available on DSPN treatment. The search was performed on PubMed, Cochrane, Semantic Scholar, Medline, Scopus, and Cochrane Library databases, including among others the terms “distal symmetrical polyneuropathy”, “neuropathic pain treatment”, “diabetic neuropathy”, “diabetes complications”, ”glycaemic control”, “antidepressants”, “opioids”, and “anticonvulsants”. Results: First-line drugs include antidepressants (selective serotonin reuptake inhibitors and tricyclic antidepressants) and pregabalin. Second- and third-line drugs include opioids and topical analgesics. While potentially effective in the treatment of neuropathic pain, opioids are not considered to be the first choice because of adverse reactions and addiction concerns. Conclusions: DSPN is a common complication in patients with diabetes, and severely affects the quality of life of these patients. Although multiple therapies are available, the guidelines and recommendations regarding the treatment of diabetic neuropathy have failed to offer a unitary consensus, which often hinders the therapeutic options in clinical practice.

Hormonal changes during pregnancy can trigger gestational diabetes (GDM), which is constantly increasing. Its main characteristic is pronounced insulin resistance, but it appears to be a multifactorial process involving several metabolic factors; taken together, the latter leads to silent or clinically evident cardiovascular (CV) events. Insulin resistance and central adiposity are of crucial importance in the development of metabolic syndrome, and they appear to correlate with CV risk factors, including hypertension and atherogenic dyslipidaemia. Hypertensive disease of pregnancy (HDP) is more likely to be an accompanying co-morbidity in pregnancies complicated with GDM. There is still inconsistent evidence as to whether or not co-existent GDM and HDP have a synergistic effects on postpartum risk of cardiometabolic disease; however, this synergism is becoming more accepted since both these conditions may promote endothelial inflammation and early atherosclerosis. Regardless of the presence or absence of the synergism between GDM and HDP, these conditions need to be dealt early enough, in order to reduce CV morbidity and to improve health outcomes for both women and their offspring.

Corneal confocal microscopy (CCM) has revealed reduced corneal nerve fiber (CNF) length and density (CNFL, CNFD) in patients with diabetes, but the spatial pattern of CNF loss has not been studied. We aimed to determine whether spatial analysis of the distribution of corneal nerve branching points (CNBPs) may contribute to improving the detection of early CNF loss. We hypothesized that early CNF decline follows a clustered rather than random distribution pattern of CNBPs. CCM, nerve conduction studies (NCS), and quantitative sensory testing (QST) were performed in a cross-sectional study including 86 patients recently diagnosed with type 2 diabetes and 47 control subjects. In addition to CNFL, CNFD, and branch density (CNBD), CNBPs were analyzed using spatial point pattern analysis (SPPA) including 10 indices and functional statistics. Compared to controls, patients with diabetes showed lower CNBP density and higher nearest neighbor distances, and all SPPA parameters indicated increased clustering of CNBPs (all P97.5th percentile of controls in up to 23.5% of patients. When combining an individual SPPA parameter with CNFL, ≥1 of 2 indices were >99th or

Background and objectives: Obstructive sleep apnea syndrome (OSAS) is associated with cardiovascular and metabolic risk factors, such as insulin resistance. Furthermore, OSAS has been associated with decreased levels of vitamin D (Vit D). The aim of the study was to assess the association between Vit D levels (expressed as 25(OH)D serum levels) and insulin resistance in patients with OSAS. Materials and Methods: Serum 25(OH)D levels were measured in consecutive subjects who had undergone polysomnography and pulmonary function testing. OSAS patients were divided into those with (homeostatic model assessment [HOMA-IR] ≥ 2) and without insulin resistance (HOMA-IR < 2). Results: Overall, 92 patients (81 males) were included in the study. OSAS patients with insulin resistance significantly differed from those without insulin resistance in terms of the body-mass index (BMI) (36.3 ± 5.8 compared to 32 ± 5.6 kg/m2, respectively, p = 0.001), apnoea-hypopnoea index (AHI) (57.4 ± 28.9 compared to 40.9 ± 27.9 events/h, respectively, p = 0.009) and indices of hypoxia during sleep. Patients with OSAS and insulin resistance had lower levels of serum 25 (OH) D compared with OSAS but without insulin resistance (19.3 ± 11.5 vs 26.7 ± 12.2 ng/mL, respectively, p = 0.005). Regression analysis demonstrated a negative association of 25(OH)D levels (β = −0.048, odds ratio [OR]: 0.953, 95% confidence interval [CI]: 0.913−0.995, p = 0.030) and a positive association of BMI (β = 0.110, OR: 1.116, 95% CI: 1.007−1.237, p = 0.036) with insulin resistance. Conclusions: Vit D insufficiency was significantly more frequent among OSAS patients with insulin resistance. Both low 25(OH)D levels and high BMI were associated with the risk of insulin resistance in this population.

Mounier-Kuhn syndrome (MKS), or tracheobronchomegaly, is a rare clinical and radiologic condition characterized by pronounced tracheobronchial dilation and recurrent lower respiratory tract infections. Tracheobronchomegaly presents when the defect extends to the central bronchi. MKS can be diagnosed in adult women when the transverse and sagittal diameters of the trachea, right mainstem bronchus, and left mainstem bronchus exceed 21, 23, 19.8, and 17.4 mm, respectively. Its diagnosis is based on chest radiograph and chest computed tomography (CT). Patients, usually middle-aged men, may be asymptomatic or present with clinical manifestations ranging from minimal symptoms with preserved lung function to severe respiratory failure. Pulmonary function tests (PFTs) typically reveal a restrictive pattern. This report presents an elderly woman with previously diagnosed pulmonary fibrosis with symptoms of increased sputum production and haemoptysis. High-resolution chest CT showed tracheal and main stem bronchi dilatation along with bronchial diverticulosis. PFTs indicated a restrictive pattern characteristic of the underlying pulmonary fibrosis. The patient is the oldest, referred to the female gender, at presentation of MKS hitherto reported. This case highlights the need to include MKS in the differential diagnosis of recurrent lower respiratory tract infections, even in older subjects.

Nikolaos Papanas1, Paschalis Steiropoulos2, Evangelia Nena2, Argyris Tzouvelekis2, Athanasios Skarlatos2, Maria Konsta2, Vasileios Vasdekis3, Efstratios Maltezos1, Demosthenes Bouros21Outpatient Clinic of Obesity, Diabetes and Metabolism, Second Department of Internal Medicine, Medical School, Democritus University of Thrace, Alexandroupolis, Greece; 2Sleep Laboratory, Department of Pneumonology, Medical School, Democritus University of Thrace, Alexandroupolis, Greece; 3Department of Statistics, Athens University of Economic and Business, Athens, GreeceAbstract: The aim of the present study was to examine the prevalence of metabolic syndrome (MS) and its components among obstructive sleep apnea (OSA) patients vs controls, as well as to investigate which of these components are strongly associated with the presence of OSA in subjects reporting symptoms indicating sleep-disordered breathing. Included were 83 consecutive male subjects, without known concomitant diseases, who visited an outpatient clinic of obesity, diabetes and metabolism. Based on polysomnography, these were divided into two groups: OSA patients (n = 53) and controls (n = 30). Parameters indicating MS, according to the NCEP ATP III criteria (blood pressure, waist circumference, glucose, triglycerides, and HDL-cholesterol levels) were evaluated in both groups. The criteria for MS were fulfilled in 49 participants. Presence of MS was significantly correlated with the presence of OSA. However, after adjustment for BMI, only serum glucose was significantly associated with the presence of OSA (P = 0.002). Conversely, the presence of MS was associated with a significant reduction in percentage of slow-wave sleep (P = 0.030). In conclusion, these results provide further evidence for the association between OSA and MS. Between subjects with MS, elevated serum glucose levels indicate a higher probability for the presence of OSA. Keywords: diabetes mellitus, glucose, metabolic syndrome, obstructive sleep apnea

Nikolaos Papanas1, Paschalis Steiropoulos2, Evangelia Nena2, Argyris Tzouvelekis2, Efstratios Maltezos1, Georgia Trakada2, Demosthenes Bouros21Outpatient Clinic of Obesity, Diabetes and Metabolism at the 2nd Department of Internal Medicine, 2Department of Pneumonology, Democritus University of Thrace, Alexandroupolis, GreeceAbstract: The aim of this study was to examine the potential correlation of sleep characteristics with glucose metabolism in nondiabetic men with obstructive sleep apnea syndrome (OSAS). Included were 31 male patients (mean age 46.7 ± 11 years), recently diagnosed with OSAS by full polysomnography. There was a significant correlation of fasting glucose and glycosylated hemoglobin (HbA1c) levels with arousal index (P = 0.047 and P = 0.014, respectively). Moreover, HbA1c levels were correlated with apnea hypopnea index (P = 0.009), a widely accepted marker of the severity of OSAS, and with percentage of sleep time with saturation of hemoglobin with oxygen as measured by pulse oximetry (SpO2)

Nikolaos Papanas, Efstratios MaltezosOutpatient Clinic of Obesity, Diabetes and Metabolism at the Second Department of Internal Medicine, Democritus University of Thrace, GreeceAbstract: Diabetic foot ulcers remain a major cause of morbidity. Significant progress has been accomplished in ulcer healing by improved management of both ischemia and neuropathy in the diabetic foot. Nevertheless, there is a vital need for further improvement. Becaplermin gel represents an important therapeutic advance for diabetic neuropathic foot ulcers with adequate blood supply. Randomized controlled trials have shown that it is effective in increasing healing rates. However, this efficacy has not translated to positive clinical experience, and the drug is not widely used. Moreover, becaplermin is an expensive medication. Even though it has repeatedly been estimated as cost-effective, its high cost may be prohibitive for some clinicians, especially in developing countries. Clearly, further work is needed to clarify whether use of becaplermin is justified in everyday clinical practice. Future research also needs to assess the potential room for improvement with becaplermin, for instance by combination with other growth factors or by exploring alternative modes of drug delivery.Keywords: becaplermin, diabetes mellitus, diabetic foot, neuropathy, PDGF

Aims. We sought to determine the association between levels of adiponectin and oxidized low-density lipoprotein (ox-LDL) in patients with diabetic nephropathy as well as their effect on carotid intima-media thickness (cIMT). Methods. Adiponectin and ox-LDL were determined in 25 diabetic patients without nephropathy and 94 patients at different stages of diabetic nephropathy including subjects on hemodialysis. cIMT was measured using real-time B-mode ultrasonography. Results. Plasma adiponectin levels increased significantly with severity of diabetic nephropathy (P=0.002), on the contrary to ox-LDL which decreased with disease severity (P

Obstructive sleep apnea syndrome (OSAS) is characterized by recurrent episodes of upper airway collapse associated with oxygen desaturation and sleep disruption. It is proposed that these periodic changes lead to molecular variations that can be detected by assessing serum biomarkers. Studies have identified inflammatory, oxidative, and metabolic perturbations attributable to sleep-disordered breathing. Given that OSAS is associated with increased cardiovascular and cerebrovascular morbidity, the ideal biomarker should enable timely recognition with the possibility of intervention. There is accumulating data on the utility of serum biomarkers for the evaluation of disease severity, prognosis, and response to treatment. However, current knowledge is limited by data collection techniques, disease complexity, and potential confounding factors. The current paper reviews the literature on the use of serum biomarkers in OSAS. It is concluded that the ideal serum biomarker still needs to be discovered, while caution is needed in the interpretation of hitherto available results.

Background. Obstructive Sleep Apnea Syndrome (OSAS) is associated with inflammation, but obesity may be a confounding factor. Thus, the aim of this study was to explore differences in serum levels of inflammation markers between obese individuals with or without OSAS. Methods. Healthy individuals (n=61) from an outpatient obesity clinic were examined by polysomnography and blood analysis, for measurement of TNF-α, IL-6, CRP, and fibrinogen levels. According to Apnea-Hypopnea Index (AHI), participants were divided into two BMI-matched groups: controls (AHI