Diabetes used to be considered as a coronary heart disease equivalence and universally classified high cardiovascular risk population. However increasing epidemiological evidence now indicates the heterogeneity of risk among the diabetic patients and imposes animportance of stratifying those with relative low-risk from high-risk ones. Despite the existing risk assessment tools, current cardivoascualr disease prevention guidelines fail to provide more detailed stratification strategies for patient with diabetes and expose them to either overtreatment or undertreatment. On the other hand, various screening modality, including novel biomarkers and subclinical asthrosclerosis scanning, including coronary calcium scanning, carotid intima-media thickness, myocardial perfusion imaging and coronary computed tomography angiography, have provided very promising usage is risk stratification. With better developed test techniques and more extensive evidence, these modalities may serve in standardized screening algorithm to improve the cardiovascular risk assessment of patients with diabetes and better instruct their individualized preventive therapy.
OBJECTIVE:Inadvertently submitting a paper to a journal that is unlikely to publish it is a waste of resources and ultimately delays dissemination of one's research. A high proportion of manuscripts are rejected by their author's first-choice journal. The aim of the present work was to review guidance provided within the literature for journal selection that might minimize the chance of manuscript rejection. We also consider papers that encompass more than one main medical science and describe the selection process that we used with a paper that was published in Cardiovascular Endocrinology. METHODS:A database search (Embase, PubMed and Medworm) was performed for all articles published in the scientific literature providing guidance on journal selection. Articles were identified that either had journal selection as their principal topic or included journal selection as part of a broader discussion of publishing. The relative performance of four free-to-use, web-based applications that claim to provide guidance on journal selection was compared. RESULTS:The searches identified 286 hits, of which 249 were in English. Of these papers, 16 discussed journal selection and a further 10 articles were identified from citations within the original 16 articles. Only one article described a comprehensive model for submission decision-making. Identification of appropriate candidate journals by various web-based applications was erratic, with the Jane database providing the most robust suggestions. CONCLUSION:Our work suggests that little attention has been focused in the scientific literature on the mechanisms that authors use to select a journal for their work. Nevertheless, scientists for the most part seem to have a good sense of where their papers are most likely to be accepted. Beyond ensuring that a manuscript fulfils all the target journal's requirements, the literature suggests that it is important to have an objective view of the scientific contribution or 'value' of your work.
Type 2 diabetes mellitus (DM) is a significant cause of premature complications and mortality in patients with cardiovascular disease (CVD). In addition to lifestyle modifications, conventional treatment of DM consists of oral hypoglycemic agents, insulin sensitizers, and subcutaneous insulin. In diabetic individuals with or at risk for CVD, aspirin and statin therapy reduce CVD morbidity and mortality. Several natural or herbal supplements have shown potential benefit in patients with CVD and DM. We provide an overview of the current guidelines for treatment of DM and CVD. We then review the literature to describe the efficacy of natural approaches to CVD risk reduction in diabetic patients, with a focus on physical activity, dietary modification, and natural/herbal supplements. Activity and diet improve cardiovascular outcomes in patients with CVD and DM. Natural and herbal supplements have potential for benefit but require further research to determine their efficacy and safety.
Nonalcoholic fatty liver disease (NAFLD) is a growing epidemic in the USA affecting ∼30% of the population. It has been closely linked to metabolic syndrome and type 2 diabetes, with strong implications for cardiovascular disease (CVD). This review focuses on the relationship between NAFLD and CVD and the proposed interactions interlinking these two diseases. This appraisal also discusses treatments targeting NAFLD in the context of CVD. NAFLD is a multisystem disease and ultimately the goals of therapy are to ameliorate CVD and prevent coronary artery disease morbidity and mortality.
Patients with diabetes have a high residual risk for cardiovascular disease (CVD) and adverse outcomes despite statin therapy and lifestyle modifications. Particular to individuals with diabetes is the pattern of elevated triglycerides, small dense low density lipoprotein cholesterol, and reduced levels of high density lipoprotein cholesterol, described as dyslipidemia of diabetes. The role of combination therapy with an additional agent such as niacin, ezetimibe, fenofibrate, and n-3 fatty acids has been studied; however, at the same time, these agents have come under criticism for their limitations. We performed a review of key trials assessing the benefit of combination therapy to reduce CVD risk from dyslipidemia. Of the currently available agents that can be used in combination with statins, ezetimibe has the most favorable risk profile, with a recent trial demonstrating modest incremental benefit when given in addition to statins. PCSK9 inhibitors are a promising category, although clinical outcome data in individuals with diabetes are pending.
As one of the leading causes of death in the USA, diabetes mellitus (DM) has become an epidemic over the past few decades. Despite the high prevalence of diagnosed DM, close to half of all people with DM are unaware of their disease. The risk of type 2 DM is determined by interplay of genetic and metabolic factors. Patients with type 2 DM have a higher risk of death from cardiovascular causes compared with their nondiabetic counterparts, and the mortality rate of DM associated cardiovascular disease is different among ethnicity groups and sex groups. Because of its adverse effect on people's health, DM also imposes an economic burden on individuals and households affected, as well as on the healthcare system. Current guidelines for cardiovascular disease prevention have focused on lifestyle management, blood pressure control, lipid control, blood glucose control, antiplatelet agent use, and tobacco use cessation.
Although metformin has been in clinical use as a diabetes medication for six decades, its mechanism of action remains uncertain [1]. Hepatic gluconeogenesis is reduced by metformin without increasing insulin secretion, inducing weight gain, or risking hypoglycemia. Widely regarded as an insulin sensitizer, the main glucose-lowering effect of metformin is to reduce inappropriate rates of hepatic glucose production [2]; effects on whole-body insulin sensitivity appear to be secondary to lowered blood glucose concentrations [3]. Suggestions that metformin reduces glucose production by the activation of enzyme AMPactivated protein kinase were subsequently challenged by genetic loss-of-function studies [4]. While rodent and tissue culture studies reported that metformin inhibited the stimulatory effect of glucagon on hepatic glucose production [5] clinical studies suggest a more complex picture [6]. Results of in-vitro and in-vivo studies from Gerald Shulman’s Yale group propose that metformin noncompetitively inhibits the redox shuttle enzyme mitochondrial glycerophosphate dehydrogenase [7]. In turn, this results in an altered hepatocellular redox state, reduced conversion of lactate and glycerol to glucose, and hence decreased hepatic gluconeogenesis. Clinical studies with delayed-release metformin, formulated to deliver the drug to the lower bowel, have implicated gut hormones (glucagon-like peptide-1, peptide YY) in the glucose-lowering effect of metformin [8,9].
Hypertension (HTN) is an important risk factor for cardiovascular disease and its many manifestations. It shares pathogenic pathways with diabetes and is part of a common metabolic entity, the metabolic syndrome. When combined with diabetes, HTN has been shown to predict and promote increased risk for cardiovascular disease events over and above each risk factor alone. Of the components of this metabolic syndrome, HTN is relatively easy to diagnose and thereby more accessible for implementing preventive and treatment strategies. The recent release of Joint National Committee-8 guidelines for the treatment of HTN has fueled a debate on treatment target goals.
Pheochromocytoma and paraganglioma are catecholamine-secreting tumours associated with major haemodynamic upheavals. The cardiovascular and other organ-related morbidity and even mortality has been ascribed to the major haemodynamic effects of these tumours. Many factors affect the nature and intensity of these haemodynamic changes. The rarity of these tumours as well as their extremely varied clinical presentation preclude conduct of randomized-controlled trials that may provide evidence in terms of these factors and the ways to predict and control them. Many retrospective studies and case reports, however, do provide some insight into their haemodynamic behaviour. Factors such as tumour pathology, associated genetic syndromes, anatomical attributes and perioperative drug therapy affect the haemodynamics of patients with these unique tumours. Knowledge of these factors and their presumed and known association with haemodynamic behaviour of the patients is important during the perioperative care of these patients. The review focuses on the tumour-related, patient-related and the perioperative care-related factors that affect the haemodynamic behaviour of these patients during the surgical removal of these tumours.
OBJECTIVE:Cardiovascular disease (CVD) complicates type 2 diabetes. Empagliflozin and liraglutide have demonstrated improved survival in patients with type 2 diabetes and established CVD. We assessed prevalence and standard of care of patients with type 2 diabetes and established CVD managed in primary care.PATIENTS AND METHODS:A total of 129 general practitioners in both rural and urban areas, responsible for 348 373 patients, identified their patients with type 2 diabetes. The identification was based on a search for International Classification of Primary Health Care 2 codes in the general practitioners' electronic patient record systems. Patients with concomitant CVD were identified and characterized.RESULTS:A total of 17 113 (4.9%) patients were diagnosed with type 2 diabetes. Type 2 diabetes with concomitant CVD was found in 3665 (21.4%) patients, with their mean age being 72 years, and 34.6% were women. Mean estimated glomerular filtration rate was 68.2 ml/min, and 22.2% had microalbuminuria or macroalbuminuria. Standard of care was fair: mean glycated hemoglobin was 52.3 mmol/mol (Diabetes Control and Complications Trial=6.9%), mean blood pressure was 131.4/75.7 mmHg, and mean low-density lipoprotein cholesterol was 2.0 mmol/l.CONCLUSION:In a nationwide database survey in primary care, the prevalence of CVD in patients with type 2 diabetes was high (21.4%). Standard of care was largely in accordance with national guidelines. Identification of eligible patients is possible with existing electronic patient record systems. Identifying this high-risk subgroup of patients with type 2 diabetes and optimizing their treatment might add further cardiovascular benefits as suggested by recent cardiovascular outcome trials.
Insulin resistance, a fundamental pathophysiological abnormality in patients with type 2 diabetes, is associated with increased cardiovascular (CV) disease risk. In diabetes management, the macrovascular impact of antihyperglycemic agents that do not improve insulin sensitivity has generally been disappointing. In contrast, glucose-lowering drugs that work as insulin sensitizing agents have been postulated to reduce CV complications. The data to support this hypothesis have, however, been inconsistent. The impact of thiazolidinediones on macrovascular events is of particular interest. In this review, we discuss the results of trials reporting CV outcomes in patients treated with thiazolidinediones. We focus on the findings of the recent Insulin Resistance Intervention after Stroke trial that demonstrated a beneficial effect of pioglitazone on CV outcomes in stroke patients with insulin resistance. We discuss the Insulin Resistance Intervention after Stroke results and its implications for clinical practice. We discuss the selective use of pioglitazone as secondary prevention to reduce CV risk in insulin resistant patients. Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
Introduction Hypercholesterolemia is a causal risk factor for cardiovascular diseases, which is recommended to be treated at least in high-risk patients. Yet, currently there is a lack of epidemiological data on the number of high-risk patients in Germany who do not respond adequately to high-dose statin monotherapy or statin therapy in combination with other lipid-lowering agents. Methods Of a total of over 2.6 million patient records from general practitioners in the IMS Disease Analyzer database, all high-risk cardiovascular patients with hypercholesterolemia who did not reach target low-density lipoprotein-cholesterol (LDL-C) levels despite at least 12 months of maximum lipid-lowering therapy and optimal medication supply (medication possession rate≥80%) were selected over a defined period. Results On the basis of the practice data, a total of 602 133 patients with a high cardiovascular risk who were treated with statin monotherapy or statin combination therapy with optimal medication supply (medication possession rate≥80%) for at least 12 months were identified. Of them, 49 406 patients received high-dose statin therapy, and 51 869 patients received statin therapy in any dose in combination with another lipid-lowering agent. A total of 79 848 high-risk patients did not reach the target LDL-C level of 70 mg/dl or less despite consistent lipid-lowering therapy; of them, 12 808 had a documented LDL-C level of at least 130 mg/dl. Conclusion The prevalence of high-risk cardiovascular patients with therapy-resistant hypercholesterolemia is substantial in Germany.
Objective This study examined the associations between 25-hydroxyvitamin D (25-OHD), dietary calcium (Ca) intake, and individual components of the metabolic syndrome (MetS). Methods We analyzed a population-based sample of 18–75-year-old adults (n=3387) from the Victorian Health Monitor survey. Results After adjustment for sociodemographic, physical, and dietary factors, as well as other MetS components, every 10 nmol/l increment in 25-OHD was associated with reduced adjusted odds ratio (AOR) of elevated triglycerides (TG) [AOR: 0.79, 95% confidence interval (CI): 0.74–0.84, P<0.001], and higher fasting plasma glucose (AOR: 0.91, 95% CI: 0.86–0.96, P=0.002). After adjustment for confounders, every 500 mg/day increment in dietary Ca intake significantly reduced the odds of elevated diastolic blood pressure (AOR: 0.80, 95% CI: 0.66–0.99, P=0.038). When nine combinations of 25-OHD and Ca tertiles were examined, certain combinations were associated with reduced AOR for elevated TG (P<0.001), when referenced against the combination of low 25-OHD (median: 33 nmol/l) and low Ca (median: 579 mg/day). At low 25-OHD, increasing Ca intake decreased the AOR for low high-density lipoprotein cholesterol in a dose-dependent manner, but at high 25-OHD; such effects of Ca were blunted. Conclusion Higher vitamin D status and Ca intake or their combination were associated with reduced odds for a number of individual MetS components.
The annual meeting of the European Group for the study of Insulin Resistance (EGIR) was held in Dublin, Ireland in May 2017. Ably organized by Dr. Mesud Hatunic, Consultant Endocrinologist at Mater Misericordiae University Hospital, the conference explored the pathophysiology and treatment of insulin resistance and extended a perspective to include aspects of clinical diabetes care including diabetic retinopathy (Dr. David Keegan, Consultant Vitreo-Retinal Surgeon, Mater University Hospital, Dublin, Ireland), monogenic forms of diabetes (Dr. Maria Byrne, Consultant in Endocrinology and Diabetes, Mater Misericordiae Hospital, Dublin, Ireland) and the impact of gastric bypass surgery (Professor Carel le Roux, Co-Director of the Metabolic Medicine Group, University College, Dublin, Ireland). The group actively welcomed the participation of members who have recently joined from the Pasteur Institute in Lille, France, including Dr. Caroline Bonner, who will co-host the Spring 2018 EGIR meeting there with Professor Francois Pattou. New members are always welcome, e-mail: egir@med.unipi.it for details.
Cardiovascular mortality has decreased by 25% in Romania in the last 10 years, but it is still high despite renewed efforts between the Romanian Cardiac Societies and the government to increase life expectancy and decrease death rates through coronary heart disease or stroke. Ranking fifth among the European countries in terms of high cardiovascular risk, according to an ESC statistic, Romania has been struggling with hypertension as the leading risk factor (39.1%) together with hypercholesterolemia (39.1%), followed by smoking (26.7%) and obesity (21.3%) 1. Another alarming fact is that the prevalence of insufficient physical activity in adults over 18 years of age is 25.3% (2010). Moreover, the prevalence of diabetes is estimated to be 11.6% in the population between 20 and 79 years of age (between 535 413 and 1 967 200 individuals). Newly reported cases represent 20.69% 2. However, in 2010, Romania joined the 'Stent for Life' program, with a tremendous impact on cardiovascular mortality, which has decreased from 13.5 to 8.15% in 2013. Currently, there are 35 public and private centers in Romania for interventional cardiology, representing an average of 0.8 percutaneous coronary intervention centers/million inhabitants (the estimated number of percutaneous coronary intervention procedures/million inhabitants is 325) 3. General practitioners are the key actors of both primary and secondary prevention, but their main role is to detect cardiovascular risk factors in the general population. School doctors are also important for the implementation of a healthy lifestyle during childhood. Secondary prevention is offered to the public through cardiologists, internal medicine specialists, and general practitioners. At the national level, primary prevention is provided by the Ministry of Health through the 'National Program for The Prevention of Chronic Diseases'. National prevention programs are also jointly developed by the Romanian Society of Cardiology (RSC), namely, the Working Group for Prevention and Rehabilitation, and the Romanian Heart Foundation. There are two national coordinators for these programs. The RSC and the Romanian Heart Foundation are members of the World Heart Federation. The Romanian Heart Foundation is a member of the European Heart Network and the National Forum for cardiovascular disease (CVD) Prevention is a member of the European Network for Smoking and Tobacco Prevention 3. Primary prevention is delivered at the national level through mass media (broadcast and digital media), but it is also enforced by law as the Parliament recently decided to ban smoking in all indoor public spaces. In primary care, including in schools, general advice for a healthy lifestyle is provided, but there is no dedicated national program. The main arena for both primary and secondary prevention is the country's hospitals, through their departments of cardiology and internal medicine. During admission and before discharge, the patient receives recommendations for the prevention and treatment of the main cardiovascular risk factors, which include printed flyers 3. Numerous associations, clubs, and foundations are also committed to promoting cardiovascular prevention, but they are not working in a synchronized and quantifiable manner. Such an initiative is 'The Athletic Club of the Romanian Society of Cardiology', a real success story in promoting daily physical activity. There are no national guidelines on the prevention of CVDs because the RSC has fully embraced and translated the European Guidelines on Cardiovascular Prevention, Dyslipidemia, or Hypertension. The use of the SCORE risk charts in both primary prevention and cardiology practice is promoted. Unfortunately, we do not have an audit system to evaluate the results of nationwide cardiovascular prevention. There is an ongoing national survey called SEPHAR, organized by the Romanian Society of Hypertension, on the prevalence and control of arterial hypertension in Romania, which is now in its third edition. Romania has also participated in the EuroASPIRE trials III, IV, which is now currently undergoing the fifth edition. There are a number of country-wide campaigns aimed at cardiovascular prevention such as 'Alianta Romania Respira', the largest national campaign designed to approve and implement the smoking ban in closed public places, or 'PROFI iubeste sanatatea', a smoking-cessation project delivered to the first private company member of National Forum for CVD Prevention. 'Romanian Heart Week' comprises of a series of events taking place during the whole week that include World Heart Day, raising awareness of the importance of physical activity. Also, 'Promenada Inimilor' (based on 'Sli na Slainte' project of Irish Heart Foundation) is a project aimed at identifying accessible walking routes and to encourage individuals of all ages to exercise as a daily part of cardiovascular prevention measures (project implemented in more than 30 cities across the country during World Heart Day). Athletic CardioClub organizes activities throughout the year and the Romanian Heart Foundation together with CardioPrevent Foundation have started a project called 'CLIPA' aimed at early detection and management of familial hypercholesterolemia. World Hypertension Day is a joint venture between Alianta Romana de Control al Hipertensiunii Arteriale (ARCHA) and the Romanian Heart Foundation, celebrating World Hypertension Day every year by checking blood pressure, determining cardiovascular risk and distributing educational materials to the population 3. In addition to these campaigns, a series of projects have been launched to raise awareness of cardiovascular risk factors such as SOS Cardio and to encourage individuals to participate in yearly controls at their general practitioner for early detection of CVDs. 'Bike for your heart' promotes physical exercise exclusively through social media channels and the 'Heart Ball' hosted at the House of the Parliament brings together decision-makers in healthcare, mass media, and political authorities to bring attention to the importance of preventive interventions to reduce cardiovascular mortality. 'Your Heart Agenda' is an educational tool for encouraging healthy habits such as fruit and vegetable intake, daily exercise routine, weight management, smoking cessation, and leisure activities. 'Young Health Programme' offers a unique focus on young individuals and primary prevention of the most common noncommunicable diseases, such as type 2 diabetes, cancer, and heart and respiratory diseases 3. Last but not the least, cardiovascular prevention is part of the training curricula in cardiology; however, few universities include it in their curriculum for students. Victor Babeş University of Medicine and Pharmacy from Timisoara also has an accredited Master in Prevention and Rehabilitation in Cardiovascular and Respiratory Diseases. The National Forum for Cardiovascular Disease Prevention also organizes a series of interdisciplinary educational conferences (cardiodiabetes-nephropneumology) called 'Master Classes' 3. In contrast, the Romanian Diabetes Society has been conducting a campaign to 'Control your Diabetes', involving two editions, one in spring and one held in conjunction with the World Diabetes Day, in autumn. The main objectives of the Campaign are to involve authorities and the media in spreading the message of awareness about the increased incidence of diabetes in Romania; to inform and educate the public of the importance of diabetes prevention, and also the effective control of diabetes and improved lifestyle for patients affected by this disease 4. The Romanian Society of Diabetes, Nutrition and Metabolic Diseases organizes a number of courses every year to increase and constantly improve the level of education of its members and specialists involved in the management of patients with diabetes 4. Currently, the main obstacle in the implementation of all CVD prevention measures is the stressful economic situation, which hinders the achievement of these goals. The RSC works according to a pre-established program, which includes among its objectives a move toward a more pragmatic approach for the issues now facing Romanian Cardiology. Specific programs have been launched and are continuously developed for each of the four major risk factors: smoking, hypertension, lack of exercise, and high cholesterol 3. The common ground on which cardiologists, diabetologists, nephrologists, and internal medicine specialists wage war on their common enemy, atherosclerosis, goes by various names according to their field of expertise. The battle is ferocious and yet the goals are not impossible to reach as these specialists not only have the necessary skills, knowledge, and determination to implement the guidelines but also the support of their national societies reunited under the Forum for CVD Prevention to achieve cardiometabolic prevention in Romania as more than just a mere midsummer's night dream. Spirits have been running high and low when it comes to mitigating the ever-present effects of atherosclerosis in our daily practice; however, hopes are high that the taming of the shrew is not an impossible feat in terms of interdisciplinary work.
The 2017 annual Oxford Diabetes Symposium was held at Keble College on 20th and 21st July. The event, which is by invitation and focused on senior diabetes specialist clinicians, was organized by Oxford physicians Dr Garry Tan and Dr Jonathan Levy. As usual, the symposium was supported by an unrestricted educational grant from Novo Nordisk (who have recently announced a major collaboration on type 2 diabetes research with the University of Oxford). News of Dr Levy’s impending retirement from full-time clinical medicine generated a warm round of applause from the invited expert audience. Dr Levy’s contribution towards the advancement of knowledge in diabetes has been substantial. Here, I present brief partial summaries of state-of-the-art lectures from world-class investigators currently engaged in cutting-edge cardiometabolic research. The presentations covered in this report address aspects of the interactions that exist between diabetes, metabolism, and cardiovascular disease. Awareness of the potential therapeutic implications of these intersections has emerged with the initial results and further analyses of recent cardiovascular outcome trials (CVOTs) of novel glucose-lowering therapies that have shown benefits on aspects of cardiovascular disease – along with some risks in certain cases – in high-risk patients with type 2 diabetes. Where relevant, some recent updates have also been included. Professor Cliff Bailey, University of Aston, UK Diabetes medications: delivery mechanisms Professor Bailey prefaced his review by reminding the audience of the treatment burden of diabetes and related disorders. He then launched into a comprehensive overview of novel aspects of diabetes pharmacotherapy starting with a drug celebrating its 60th anniversary and that remains a cornerstone of therapy. Metformin: Compared with immediate-release metformin, metformin XR (extended release) has a lower propensity to cause gastrointestinal side-effects conferred by a dual hydrophobic polymer matrix. Metformin DR (delayed release) involves pH-dependent dissolution. No stomach/duodenal absorption occurs before arrival in the ileum. The lower pharmacokinetic profile of metformin DR compared with metformin XR reduces systemic exposure while maintaining lower blood lactate concentrations. Intestinal actions of metformin are implicated in the improved potency of metformin DR. On a more general note, fixed-dose combinations provide the metformin component essentially free of acquisition costs. Glucagon-like peptide 1 (GLP-1) analogs: Professor Bailey reviewed the technology behind an implantable subcutaneous mini-pump that delivers exenatide (ITCA 650). An osmotic engine drives a plunger releasing exenatide for up to 12 months. Note that the Food and Drug Administration (FDA) recently rejected the product in a complete response letter to the manufacturer (Intarcia). The cardiovascular effects of weekly injectable semaglutide were reported recently in SUSTAIN-6. Oral semaglutide is a novel GLP-1 analog that has shown efficacy in reducing blood glucose in phase 2 clinical trials. Coformulations: Fixed-ratio combinations, insulin analogs, and GLP-1 agonists include IdegLira: additive effect of insulin degludec and liraglutide, helps prevents insulin-induced weight gain with lower insulin doses and fewer episodes of hypoglycemia and iGlarlixi (insulin glargine U100+lixisenatide). Note that peptide stability and solubility are highly pH dependent. Various therapeutic combinations have been explored; for example, pramlintide–metreleptin, which was discontinued in 2011 because of waning effects/higher requirements for metreleptin. Designer peptides: This approach seeks to exploit the weight-reducing potential of epitopes in multiagonist single-molecule approaches; for example, chimeric peptides, such as glucagon-GLP-1-GIP (glucose-dependent insulinotropic peptide). Insulin receptor activators: Small molecules that mimic insulin action. Sequential binding of insulin on one α/β subunit and then the next results in conformational change in the β subunit with exposure of tyrosine moieties for phosphorylation. Early insulin signaling enhancers with multiple sites of potentiation of insulin signaling in insulin-resistant states; includes non-peptide insulin receptor activators. A small molecular adiponectin receptor agonist (AR1 and AR2 receptors) improves lipid profiles in db/db mice. Other topics covered in Professor Bailey’s masterful overview included novel insulin-delivery options; biosimilar insulins including biosimilar insulins glargine (abasaglar) and biosimilar lispro; high strength (U200 300 400) insulins; very long-acting insulins; ultrafast-acting insulins; inhaled/buccal/oral insulins; smart (glucose-responsive) insulins; transcutaneous patch insulin delivery; devices including smartphone-enabled pen injector devices and insulin pumps; and nasal glucagon. Professor Rury Holman, University of Oxford, UK Heart failure in diabetes: the elephant in the room Professor Holman addressed the increasing awareness of the clinical importance of heart failure in patients with diabetes. He started by reminding the delegates of the wealth of data showing the appreciable (two-fold or more; greater in women) excess risk of heart failure that has been found in observational studies and interventional trials in patients with type 2 diabetes. Heart failure in the context of type 2 diabetes is associated with impaired functional status, renal function, autonomic neuropathy, pulmonary dysfunction, left ventricular diastolic dysfunction, and impaired myocardial metabolism. A first episode of heart failure is associated with an increased risk of diabetes, suggesting a bidirectional association. In terms of iatrogenic heart failure in diabetes, thiazolidinediones may carry a higher risk of heart failure than is generally believed. Professor Holman then reviewed the mixed results of recent CVOTs of various glucose-lowering drugs from the dipeptidyl peptidase-4 inhibitor, GLP-1 receptor agonist and sodium–glucose cotransporter 2 (SGLT-2) inhibitor classes including SAVOR-TIMI 53, EXAMINE, TECOS, ELIXA, EMPA-REG OUTCOME, LEADER, SUSTAIN-6, and CANVAS from the heart failure perspective. Data on heart failure risk (increased by saxagliptin), neutrality (lixisenatide, liraglutide), and benefits (empagliflozin, canagliflozin) were highlighted. The effects of SGLT-2 inhibitors on heart failure in the absence of diabetes are now being explored. Professor Holman also presented relevant recent clinical trial data on other aspects of heart failure therapy – for example, combined angiotensin–neprilysin inhibitors that target both arms of the renin–angiotensin–aldosterone system. Professor Naveed Sattar, University of Glasgow, UK The changing face of diabetes complications Professor Sattar offered the view that there is both ‘good news and bad news in diabetes’. First, there is a higher incidence of diabetes because patients are being kept alive; second, the prevalence of diabetes is also increasing – dietary issues being the main problem – a major public health issue. Diabetes approximately doubles the risk of cardiovascular disease. However, there is appreciable heterogeneity: individual risk varies by duration, absence or presence of renal disease, etc. The controversy on whether diabetes should be considered a coronary heart disease risk equivalent has shifted towards the negative in recent years. Earlier diagnosis – evidenced by fewer microvascular complications at diagnosis than in previous decades – allied to better glucose control and early use of statins and better control of blood pressure, has reduced the risk of myocardial infarction. Life expectancy is no longer so markedly reduced by diabetes as it was in previous eras. Nonetheless, according to data from the Emerging Risk Factors Collaboration, a 50 year old with diabetes died, on average, 6 years earlier than a counterpart without diabetes, with about 40% of the difference in survival attributable to excess nonvascular deaths. Heart failure and peripheral arterial disease are the most common initial manifestations of cardiovascular disease in type 2 diabetes. Professor Sattar noted that Asian patients tend to be less obese at diagnosis than White counterparts and pointed to evidence of the relevance of differences in adipocyte physiology observed in the GlasVEGAS (Glasgow Visceral and Ectopic Fat With Weight Gain in South AsianS) study. He also noted than risk of type 2 diabetes comes with less weight gain in men than women speculating that perhaps women may have to acquire even more adiposity to overcome their inherent metabolic advantages over men. Younger patients with type 2 diabetes face cardiometabolic risks from the metabolic syndrome – that is, obesity, hypertension, and dyslipidemia with evidence of early emergence of vascular complications. Professor Steve Bain, University of Swansea, UK Cardiovascular outcomes in diabetes Professor Bain reiterated the message that diabetes approximately doubles the risk of vascular disease and briefly reviewed some controversial aspects of the UGDP and PROactive trials along with details of the controversy of the cardiovascular effects of rosiglitazone more recently. The latter issue prompted the requirement to establish cardiovascular safety of new diabetes therapies issued as guidance by the FDA in 2008. This move generated a series of informative large CVOTs of diabetes medications that are transforming the therapeutic landscape. Professor Bain explained the aim of ‘glycemic equipoise’ in safety studies of diabetes drugs – that is, the aim being to minimize glycemic differences between the medication of interest and the comparator treatment groups. Generally, the difference achieved in the mean glycated hemoglobin between the groups has been around 0.2–0.4% (more for SUSTAIN-6, which was associated with a retinopathy safety signal, possibly related to rapid glucose lowering). As new therapies are studied on a background of current standard of care, which incorporates well-established multifactorial risk factor management, diabetes CVOTs are biased against the probability of showing cardiovascular benefit of new therapies. This approach contrasts with standard cardiovascular benefit trials. Professor Bain reviewed relevant aspects of recent diabetes CVOTs, noting that superiority was not prespecified in SUSTAIN-6; the driver of benefit was a reduction in nonfatal stroke with a nonsignificant reduction in nonfatal myocardial infarction. There was no reduction in cardiovascular deaths during the short duration (2.1 years) of the trial. Professor Bain explained that the complexities of the design of CANVAS reflected a learning experience so shortly after issuance of the 2008 FDA cardiovascular safety guidance, CANVAS being a combination of two studies. Although CANVAS showed no suggestion of a stroke signal (c.f. EMPA-REG OUTCOME), the hazard ratio for lower-extremity amputations was 1.97 (2.03 for major amputations; 29% of the total). Although it is possible that the amputation safety signal could be a class effect of SGLT-2 inhibitors, it was considered unlikely to have been missed in EMPA-REG OUTCOME. Professor Bain speculated about the potential for greater levels of hemoconcentration and peripheral thrombosis in CANVAS, reflecting the greater potency of canagliflozin at the highest dose. Professor Bain also discussed renal function in the context of some of the trials and looked at reports from ongoing and new CVOTs of glucose-lowering therapies. The neutrality of exenatide in therapy on cardiovascular events in FREEDOM and EXCEL was noted as top-line results that have been presented subsequently in detail at the European Association for the Study of Diabetes conference in Lisbon. DEVOTE was a double-blind, treat-to-target, event-driven CVOT of insulin degludec versus insulin glargine U100. The hazard ratio three-point major adverse cardiovascular events for insulin degludec was noninferior (0.91, 95% confidence interval: 0.78–1.06, P=0.209) alongside a statistically significant 37% reduction in adjudicated severe hypoglycemia (P<0.001). It was noted that regulatory authorities are also interested in real-world data in addition to data from CVOTs. As for the impact of these CVOTs on clinical diabetes management guidelines, expert groups in some countries have already modified their advice in suggesting the use of glucose-lowering drugs with evidence from CVOTs to reduce the toll from cardiovascular disease.
We herewith aimed to explore the association of premature graying, androgenic alopecia (AGA), and hair thinning with coronary artery disease (CAD) in young (≤40 years) male individuals from Western India. PATIENTS AND METHODS:In this prospective, case-control study, 1380 male individuals from a super speciality cardiac care center were enrolled, of which 468 were established cases of CAD and 912 were age-matched healthy male individuals not having history of any major illness including CAD. Details of demographics, cardiovascular risk factors, and cutaneous markers were collected for both the groups. RESULTS:Prevalence of hypertension (30.3 vs. 13.6%), obesity (28.8 vs. 12.2%), hair thinning (36.3 vs. 14.6%), premature graying (49.6 vs. 29.9%), AGA (49.1 vs. 27.4%), and lipid abnormalities (total cholesterol - 16.7 vs. 8.8%; low-density lipoprotein - 7.3 vs. 2.2%; and high-density lipoprotein - 92.5 vs. 88.7%) were higher in cases as compared with control. Multiple logistic regression analysis showed that AGA [5.619, 95% confidence interval (CI): 4.025-7.845, P<0.0001] is the strongest predictor of CAD among young Asian male individuals, closely followed by premature graying (5.267, 95% CI: 3.716-7.466, P<0.0001), obesity (4.133, 95% CI: 2.839-6.018, P<0.0001), and hair thinning (3.36, 95% CI: 2.452-4.621, P<0.0001). SYNTAX score, left ventricle ejection fraction, and degree of disease severity were also found to be independent associates of premature graying and AGA. CONCLUSION:Our findings support the hypothesis that cutaneous markers are independently associated with underlying CAD irrespective of other classical cardiovascular risk factors. This, in combination with classical markers, could be effectively used for early identification and risk stratification of young patients with occult or established CAD.
Chronic kidney disease (CKD) is a heterogeneous range of disorders affecting up to 11% of the world's population. The majority of patients with CKD die of cardiovascular disease (CVD) before progressing to end-stage renal disease. CKD patients have an increased risk of atherosclerotic disease as well as a unique cardiovascular phenotype. There remains no clear aetiology for these issues and a better understanding of the pathophysiology of CKD-associated CVD is urgently needed. Although nonanimal studies can provide insights into the nature of disease, the whole-organism nature of CKD-associated CVD means that high-quality animal models, at least for the immediate future, are likely to remain a key tool in improving our understanding in this area. We will discuss the methods used to induce renal impairment in rodents and the methods available to assess cardiovascular phenotype and in each case describe the applicability to humans.
One of the biggest current challenges in managing an ageing cohort living with the HIV is handling dyslipidaemia, diabetes, metabolic syndrome and nonalcoholic fatty liver disease. Combination antiretroviral therapy decrease mortality and morbidity in HIV patients, but lead to increase in insulin resistance, dyslipidaemia, abnormalities of fat distribution and high risk of cardiovascular disease. Therefore, a metabolic clinic was established for individuals living with HIV in the Milton Keynes University Hospital NHS Foundation Trust. The clinic meets considerable demands by service users and hence has the potential to be popular. This review focuses on the importance of the development of a metabolic clinic for the purpose of audit, research, teaching and exchange of knowledge between HIV specialists and the metabolic team in the management of complex cases. Therefore, the metabolic clinic should be an integral part of HIV services especially as the cohort of the 'older' HIV population increases. Cardiovasc Endocrinol 6: 109-112 Copyright (C) 2017 Wolters Kluwer Health, Inc. All rights reserved.
