The cardiometabolic syndrome and sarcopenic obesity in older persons

The aging of the world's population is a major contributor to the growing prevalence of the cardiometabolic syndrome (CMS) because older persons are more affected by the constellation of cardiovascular risk factors that constitute the syndrome. The prevalence of CMS has been related to the increasing prevalence of obesity, which is growing progressively even among older age groups. Indeed, obesity and aging are 2 overlapping mounting public health problems. It is currently accepted that CMS predicts cardiovascular mortality and/or the development of type 2 diabetes mellitus, and this is also true in studies including older persons. CMS is further complicated by modifications in body composition and fat redistribution during aging; older adults are at higher risk for developing central obesity and sarcopenia or sarcopenic obesity, a condition characterized by an important reduction in lean body mass associated with obesity, linked to an increased production of inflammatory adipokines that may alter insulin sensitivity and muscle mass and strength. A better understanding of the pathophysiologic mechanisms of sarcopenic obesity may help to elucidate the complex relationship between CMS and mortality/morbidity in older adults.     

Diabetes in the Elderly

Older adults with diabetes constitute a rapidly increasing population in the United States. Cardiovascular diseases occur at higher frequency in this population. Until recently, optimal goals of glycemic control as well as risk factor management (hypertension and lipids) to prevent cardiovascular morbidity and mortality in older adults with diabetes were unclear. Several clinical trials in recent years have shown minimal benefits and in certain populations (e.g. with high co-morbidities), increased risk for poor cardiovascular outcomes with tight glycemic and blood pressure control. Further analysis of these data has suggested that cardiovascular benefits are likely to be present in younger and healthier cohort. Thus management of chronic diseases in older adults with diabetes begs for moderation and individualized planning to gain benefits and avoid harm.     

COVID-19 and Older Adults: What We Know

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a novel virus that causes COVID-19 infection, has recently emerged and caused a deadly pandemic. Studies have shown that this virus causes worse outcomes and a higher mortality rate in older adults and those with comorbidities such as hypertension, cardiovascular disease, diabetes, chronic respiratory disease, and chronic kidney disease (CKD). A significant percentage of older American adults have these diseases, putting them at a higher risk of infection. Additionally, many adults with hypertension, diabetes, and CKD are placed on angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers. Studies have shown that these medications upregulate the ACE-2 receptor, the very receptor that the SARS-CoV-2 virus uses to enter host cells. Although it has been hypothesized that this may cause a further increased risk of infection, more studies on the role of these medications in COVID-19 infections are necessary. In this review, we discuss the transmission, symptomatology, and mortality of COVID-19 as they relate to older adults, and possible treatments that are currently under investigation. J Am Geriatr Soc 68:926–929, 2020     

Antibiotics,gut microbiome and obesity

Antibiotics have been hailed by many as “miracle drugs” that have been effectively treating infectious diseases for over a century, leading to a marked reduction in morbidity and mortality. However, with the increasing use of antibiotics, we are now faced not only with the increasing threat of antibiotic resistance, but also with a rising concern about potential long‐term effects of antibiotics on human health, including the development of obesity. The obesity pandemic continues to increase, a problem that affects both adults and children alike. Disruptions to the gut microbiome have been linked to a multitude of adverse conditions, including obesity, type 2 diabetes, inflammatory bowel diseases, anxiety, autism, allergies, and autoimmune diseases. This review focuses on the association between antibiotics and obesity, and the role of the gut microbiome. There is strong evidence supporting the role of antibiotics in the development of obesity in well‐controlled animal models. However, evidence for this link in humans is still inconclusive, and we need further well‐designed clinical trials to clarify this association.     

Management of diabetes in older adults

Enhanced life expectancy and the aging of society have conspired with rising rates of obesity and physical inactivity to cause an unprecedented increase in diabetes prevalence worldwide. The disease and its chronic complications have unique presentations and challenges in the elderly. Postprandial hyperglycemia may be the predominant manifestation, comorbid health conditions are often present, and the risk of cardiovascular disease is vastly increased. Periodic screening is essential for early diagnosis and proper treatment. The principles of multidisciplinary management emphasizing nutrition, exercise, education, psychosocial care, attention to concomitant metabolic risk factors, and prudent use of pharmacologic agents are the mainstay of therapy for older adults. Treatment should be tailored to the individual patient, and the assistance of family and caregivers should be combined with rational utilization of community resources. An evidence-based, comprehensive, and proactive approach is needed to reduce the burden of morbidity and mortality from diabetes in the elderly.     

Is China facing an obesity epidemic and the consequences? The trends in obesity and chronic disease in China

BACKGROUND: Over the past two decades, China has enjoyed impressive economic development, and her citizens have experienced many remarked changes in their lifestyle. These changes are often associated with an increase in obesity and chronic disease. METHODS: In this meta-analysis, based on nationally representative data, we studied the current prevalence of obesity and the trends in obesity, mortality and morbidity in China. RESULTS: Between 1992 and 2002, the prevalence of overweight and obesity increased in all gender and age groups and in all geographic areas. Using the World Health Organization body mass index cut points, the combined prevalence of overweight and obesity increased from 14.6 to 21.8%. The Chinese obesity standard shows an increase from 20.0 to 29.9%. The annual increase rate was highest in men aged 18-44 years and women aged 45-59 years (approximately 1.6 and 1.0% points, respectively). In general, male subjects, urban residents, and high-income groups had a greater increase. With the increase in overweight and obesity, obesity-, and diet-related chronic diseases (e.g., hypertension, cardiovascular disease (CVD), and type 2 diabetes) also increased over the past decade and became a more important preventable cause of death. Hypertension increased from 14.4% in 1991 to 18.8% in 2002 in adults; in older adults aged 35-74 years, it increased from 19.7 to 28.6%. Between 1993 and 2003, the prevalence of CVD increased from 31.4 to 50.0%; diabetes increased from 1.9 to 5.6%. During 1990-2003, although total mortality rate (per 100 000) decreased, overall the mortality rate and contribution (as percentages) to total death of obesity-related chronic disease increased, in particular, in rural areas. Mortality rate (per 100 000) of CVD increased from 128 to 145 and its contribution to total death, 27 to 32%, in rural areas; the figures decreased slightly in urban areas. The mortality rate of 'nutrition, endocrinology and metabolism-related disease' (NEMD) increased in both rural and urban areas between 1990 and 2000, 8.0 to 10.6 and 4.9 to 5.3, respectively. The current prevalence of hypertension, dyslipidaemia, metabolic syndrome, and diabetes among Chinese adults is approximately 20, 20, 15, and 3%, respectively. CONCLUSION: The prevalence of overweight and obesity and obesity-related chronic diseases have increased in China in the past decade. Our findings provide useful information for the projection of future trends and the formulation of national strategies and programmes that can address the challenges of the growing obesity and chronic disease epidemic.     

Evaluating glucose-lowering treatment in older people with diabetes: Lessons from the IMPERIUM trial

Understanding the benefits and risks of treatments to be used by older individuals (≥65 years old) is critical for informed therapeutic decisions. Glucose-lowering therapy for older patients with diabetes should be tailored to suit their clinical condition, comorbidities and impaired functional status, including varying degrees of frailty. However, despite the rapidly growing population of older adults with diabetes, there are few dedicated clinical trials evaluating glucose-lowering treatment in older people. Conducting clinical trials in the older population poses multiple significant challenges. Despite the general agreement that individualizing treatment goals and avoiding hypoglycaemia is paramount for the therapy of older people with diabetes, there are conflicting perspectives on specific glycaemic targets that should be adopted and on use of specific drugs and treatment strategies. Assessment of functional status, frailty and comorbidities is not routinely performed in diabetes trials, contributing to insufficient characterization of older study participants. Moreover, significant operational barriers and problems make successful enrolment and completion of such studies difficult. In this review paper, we summarize the current guidelines and literature on conducting such trials, as well as the learnings from our own clinical trial (IMPERIUM) that assessed different glucose-lowering strategies in older people with type 2 diabetes. We discuss the importance of strategies to improve study design, enrolment and attrition. Apart from summarizing some practical advice to facilitate the successful conduct of studies, we highlight key gaps and needs that warrant further research.     

The impact of immuno-aging on SARS-CoV-2 vaccine development

The SARS-CoV-2 pandemic has almost 56 million confirmed cases resulting in over 1.3 million deaths as of November 2020. This infection has proved more deadly to older adults (those >65 years of age) and those with immunocompromising conditions. The worldwide population aged 65 years and older is increasing, and the total number of aged individuals will outnumber those younger than 65 years by the year 2050. Aging is associated with a decline in immune function and chronic activation of inflammation that contributes to enhanced viral susceptibility and reduced responses to vaccination. Here we briefly review the pathogenicity of the virus, epidemiology and clinical response, and the underlying mechanisms of human aging in improving vaccination. We review current methods to improve vaccination in the older adults using novel vaccine platforms and adjuvant systems. We conclude by summarizing the existing clinical trials for a SARS-CoV-2 vaccine and discussing how to address the unique challenges for vaccine development presented with an aging immune system.

     

Gut microbiota in a population highly affected by obesity and type 2 diabetes and susceptibility to COVID-19

Coronavirus disease 2019 (COVID-19) is a disease produced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and it is currently causing a catastrophic pandemic affecting humans worldwide. This disease has been lethal for approximately 3.12 million people around the world since January 2020. Globally, among the most affected countries, Mexico ranks third in deaths after the United States of America and Brazil. Although the high number of deceased people might also be explained by social aspects and lifestyle customs in Mexico, there is a relationship between this high proportion of deaths and comorbidities such as high blood pressure (HBP), type 2 diabetes, obesity, and metabolic syndrome. The official epidemiological figures reported by the Mexican government have indicated that 18.4% of the population suffers from HBP, close to 10.3% of adults suffer from type 2 diabetes, and approximately 36.1% of the population suffers from obesity. Disbalances in the gut microbiota (GM) have been associated with these diseases and with COVID-19 severity, presumably due to inflammatory dysfunction. Recent data about the association between GM dysbiosis and metabolic diseases could suggest that the high levels of susceptibility to SARS-CoV-2 infection and COVID-19 morbidity in the Mexican population are primarily due to the prevalence of type 2 diabetes, obesity, and metabolic syndrome.     

Evidence of physical activity participation among men and women in the countries of the Gulf Cooperation Council: a review

Rapid socioeconomic development in the countries of the Gulf Cooperation Council (GCC) has resulted in demographic and epidemiological transitions, with obesity, diabetes and other chronic diseases becoming the leading causes of morbidity and mortality. This emerging disease pattern is often attributed to physically inactive lifestyles. Given that there is no consolidated evidence on physical activity participation, we reviewed studies to examine prevalence and gender differences among GCC adults. PubMed, CINAHL and reference list searches identified eight relevant studies. Based on the best‐available data, the prevalence of adults being physically active for at least 150 min week^?1 (based on the international standard definition) ranged from 39.0% to 42.1% for men and 26.3% to 28.4% for women. Men were significantly more active than were women. Prevalence estimates for participation in physical activity in the GCC States are considerably lower than those for many developed countries. Studies using standardized methodologies with nationally representative samples are urgently required. Identifying prevalence and gender variations provides the basis for understanding the unique socio‐cultural and environmental factors contributing to physical inactivity among adults in the countries of the GCC. This understanding must then inform population‐health strategies to address the rising prevalence of obesity, type 2 diabetes and other chronic diseases.     

Early intervention and intensive management of patients with diabetes,cardiorenal, and metabolic diseases

Increasing rates of obesity and diabetes have driven corresponding increases in related cardiorenal and metabolic diseases. In many patients, these conditions occur together, further increasing morbidity and mortality risks to the individual. Yet all too often, the risk factors for these disorders are not addressed promptly in clinical practice, leading to irreversible pathologic progression. To address this gap, we convened a Task Force of experts in cardiology, nephrology, endocrinology, and primary care to develop recommendations for early identification and intervention in obesity, diabetes, and other cardiorenal and metabolic diseases. The recommendations include screening and diagnosis, early interventions with lifestyle, and when and how to implement medical therapies. These recommendations are organized into primary and secondary prevention along the continuum from obesity through the metabolic syndrome, prediabetes, diabetes, hypertension, dyslipidemia, nonalcoholic fatty liver disease (NAFLD), atherosclerotic cardiovascular disease (ASCVD) and atrial fibrillation, chronic kidney disease (CKD), and heart failure (HF). The goal of early and intensive intervention is primary prevention of comorbidities or secondary prevention to decrease further worsening of disease and reduce morbidity and mortality. These efforts will reduce clinical inertia and may improve patients' well-being and adherence.     

Semaglutide for the treatment of overweight and obesity: A review

Obesity is a chronic, relapsing disease associated with multiple complications and a substantial morbidity, mortality and health care burden. Pharmacological treatments for obesity provide a valuable adjunct to lifestyle intervention, which often achieves only limited weight loss that is difficult to maintain. The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial programme is evaluating once-weekly subcutaneous semaglutide 2.4 mg (a glucagon-like peptide-1 analogue) in people with overweight or obesity. Across STEP 1, 3, 4 and 8, semaglutide 2.4 mg was associated with mean weight losses of 14.9%-17.4% in individuals with overweight or obesity without type 2 diabetes from baseline to week 68; 69%-79% of participants achieved ≥10% weight loss with semaglutide 2.4 mg (vs. 12%-27% with placebo) and 51%-64% achieved ≥15% weight loss (vs. 5%-13% with placebo). In STEP 5, mean weight loss was −15.2% with semaglutide 2.4 mg versus −2.6% with placebo from baseline to week 104. In STEP 2 (individuals with overweight or obesity, and type 2 diabetes), mean weight loss was −9.6% with semaglutide 2.4 mg versus −3.4% with placebo from baseline to week 68. Improvements in cardiometabolic risk factors, including high blood pressure, atherogenic lipids and benefits on physical function and quality of life were seen with semaglutide 2.4 mg. The safety profile of semaglutide 2.4 mg was consistent across trials, primarily gastrointestinal adverse events. The magnitude of weight loss reported in the STEP trials offers the potential for clinically relevant improvement for individuals with obesity-related diseases.     

Severe COVID-19 and aging: are monocytes the key?

The ongoing pandemic severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a disproportionate number of severe cases and deaths in older adults. Severe SARS-CoV-2-associated disease (coronavirus disease 2019 (COVID-19)) was declared a pandemic by the World Health Organization in March 2020 and is characterized by cytokine storm, acute respiratory distress syndrome, and in some cases by systemic inflammation–related pathology. Currently, our knowledge of the determinants of severe COVID-19 is primarily observational. Here, I review emerging evidence to argue that monocytes, a circulating innate immune cell, are principal players in cytokine storm and associated pathologies in COVID-19. I also describe changes in monocyte function and phenotype that are characteristic of both aging and severe COVID-19, which suggests a potential mechanism underlying increased morbidity and mortality due to SARS-CoV-2 infection in older adults. The innate immune system is therefore a potentially important target for therapeutic treatment of COVID-19, but experimental studies are needed, and SARS-CoV-2 presents unique challenges for pre-clinical and mechanistic studies in vivo. The immediate establishment of colonies of SARS-CoV-2-susceptible animal models for aging studies, as well as strong collaborative efforts in the geroscience community, will be required in order to develop the therapies needed to combat severe COVID-19 in older adult populations.

     

Evolving concepts of cardiovascular disease prevention in older adults

Cardiovascular disease is the leading cause of morbidity and mortality in older adults. Clinical and subclinical disease increase in prevalence with age and impose a significant burden on this population. Given the increase in absolute cardiovascular risk with age, there is tremendous potential for benefit from primary and secondary cardiovascular disease preventive interventions in the elderly. Recent clinical trials focusing on preventive therapies targeting cardiovascular disease risk factors, including hypertension and cholesterol, have shed light on the potential gains from these measures in older adults. This article briefly reviews several of the current issues and unanswered questions relating to cardiovascular disease prevention in the elderly.     

The metabolic syndrome: prevalence, CHD risk, and treatment

An increased risk of coronary heart disease (CHD) morbidity and mortality is associated with the metabolic syndrome, a condition characterized by the concomitant presence of several abnormalities, including abdominal obesity, dyslipidemia, hypertension, insulin resistance (with or without glucose intolerance or diabetes), microalbuminuria, prothrombotic, and proinflammatory states. Estimates of the prevalence of the metabolic syndrome indicate that this condition is now common and likely to increase dramatically over the coming decades, in parallel with greater rates of obesity and Type 2 diabetes. Risk factors for the metabolic syndrome are already present in obese children and adolescents. Thus, identifying and treating all affected individuals promptly and optimally are critical to ensure that this potentially challenging healthcare burden is minimized. Here, we review the prevalence of the metabolic syndrome, dyslipidemias, and CHD risk. Although changes in lifestyle are fundamental to reducing many of the CHD risk factors associated with the metabolic syndrome, pharmacologic interventions also play an important role. Retrospective subanalyses of the effects of statins on coronary event rates and lipid levels in patients with the metabolic syndrome included in clinical trials indicate that these agents are beneficial in correcting the extensive lipid abnormalities that are frequently present in these individuals. However, the optimal management of metabolic syndrome dyslipidemia will depend on the outcomes of future prospective clinical trials. This review examines the underlying causes and prevalence of the metabolic syndrome and its impact on CHD morbidity and mortality and discusses the role of statins in optimizing its management.     

Clinical considerations in the management of non-alcoholic steatohepatitis cirrhosis pre-and post-transplant: A multi-system challenge

Non-alcoholic steatohepatitis(NASH) is the most common chronic liver disease worldwide, and the fastest growing indication for liver transplantation in the United States. NASH is now the leading etiology for liver transplantation in women, the second leading indication for men, and the most common cause amongst recipients aged 65 years and older. Patients with end-stage liver disease related to NASH represent a unique and challenging patient population due the high incidence of associated comorbid diseases, including obesity, type 2 diabetes(T2 D), and hypertension. These challenges manifest in the pre-liver transplantation period with increased waitlist times and waitlist mortality. Furthermore, these patients carry considerable risk of morbidity and mortality both before after liver transplantation, with high rates of T2 D, cardiovascular disease, chronic kidney disease, poor nutrition, and disease recurrence. Successful transplantation for these patients requires identification and management of their comorbidities in the face of liver failure. Multidisciplinary evaluations include a thorough pre-transplant workup with a complete cardiac evaluation, control of diabetes, nutritional support, and even, potentially, consultation with a bariatric surgeon. This article provides a comprehensive review of the conditions and challenges facing patients with NASH cirrhosis undergoing liver transplantation and provides recommendations for evaluation and management to optimize them before liver transplantation to produce successful outcomes.     

Multifactorial Intervention to Reduce Cardiovascular Events in Type 2 Diabetes

Type 2 diabetes is associated with a significantly increased risk of cardiovascular disease (CVD) morbidity and mortality. Although several clinical trials have evaluated the effects of interventions to reduce CVD risk in people with diabetes, such studies are primarily conducted to target individual risk factors such as hypertension, hyperglycemia, and dyslipidemia rather than using a multifactorial interventional approach. Existing clinical trial data suggest that intensive multifactorial interventions that target several important risk factors simultaneously result in a significantly greater risk reduction in CVD risk compared with single risk factor interventions. However, few studies have evaluated the efficacy and effectiveness of such interventions on CVD hard end points. A multidisciplinary team management of diabetes should focus on weight control, diet, physical activity, diabetes education, and adherence to pharmacotherapy. An individually tailored aggressive management program to reduce multiple CVD risk factors simultaneously has great potential to prevent CVD morbidity and mortality among patients with type 2 diabetes.     

Clinical trial to test the efficacy of melatonin in COVID-19

The pharmacological properties of melatonin are well known. However, there is noticeable the lack of clinical trials that confirm the efficacy, security, absence of side effects in the short and long term, and the effective doses of melatonin. This point is especially important in diseases with high morbidity and mortality including COVID-19. There is not treatment for COVID-19, and several anti-inflammatory and antiviral molecules are being tested, and different vaccines are in preparation. Although the SARS-CoV-2 pandemic is apparently improving, it is expected new resurges next fall. Thus, looking for an effective treatment of COVID-19 is mandatory. Melatonin has significant anti-inflammatory, antioxidant, and mitochondrial protective effects, and its efficacy has been demonstrated in multiple experimental models of disease and in a clinical trial in sepsis. Because COVID-19 courses with a severe septic response, multiple reviews proposing melatonin as a treatment for COVID-19 have been published. Nevertheless, there is a lack of experimental and clinical data on the use of melatonin on SARS-CoV-2 infection. Accordingly, we designed a clinical trial with an injectable formulation of melatonin for intravenous perfusion in ICU patients suffering from COVID-19 that has been just approved by the Spanish Agency of Medicines and Medical Devices (AEMPS). The trial will allow by the first time understand the doses and efficacy of melatonin against COVID-19.     

The Psychosocial Challenges and Care of Older Adults with Diabetes: “Can’t Do What I Used To Do; Can’t Be Who I Once Was”

The prevalence of diabetes is increasing in older populations worldwide. Older adults with diabetes have unique psychosocial and medical challenges that impact self-care and glycemic control. These challenges may include psychological factors such as depression or anxiety, social factors such loss of independence and removal from home environment/placement in a facility, and medical factors such as multiple comorbidities and polypharmacy. Importantly, these challenges interact and complicate the everyday life of the older adult with diabetes. Thus, timely identification and interventions for psychosocial and medical challenges are a necessary component of diabetes care. This review summarizes the current literature, research findings, and clinical recommendations for psychosocial care in older adults with diabetes.     

Prevention of strokes

Stroke is a major cause of morbidity and mortality. Risk factors for stroke have been determined through prospective epidemiologic study. Control of risk factors has been demonstrated to reduce stroke incidence, either through controlled trials or inferred from observational studies. In the past few years, new approaches to the treatment of established risk factors have been discovered. These include aggressive control of hypertension in diabetes patients, prevention of type 2 diabetes through lifestyle modification, carotid endarterectomy for moderate symptomatic carotid stenosis, encouragement of a high level of physical activity, and control of abdominal obesity and elevated body mass index. In addition, new strategies for stroke prevention have been identified, including encouragement of a diet high in fruits, vegetables, whole grains, and omega-3 fatty acids, the use of vitamins B12, B6, and folic acid in hyperhomocysteinemia, and moderate alcohol consumption. Clinical trial data support the use of hydroxymethyl-coenzyme A inhibitors in patients with coronary artery disease, and ramipril in high-risk patients with coronary artery disease and diabetes, for the primary prevention of stroke. New risk factors for stroke are being investigated, including the role of chronic inflammation and infection, and these may provide future strategies for stroke prevention.