Disrupted Nitric Oxide Metabolism from Type II Diabetes and Acute Exposure to Particulate Air Pollution

Type II diabetes is an established cause of vascular impairment. Particulate air pollution is known to exacerbate cardiovascular and respiratory conditions, particularly in susceptible populations. This study set out to determine the impact of exposure to traffic pollution, with and without particle filtration, on vascular endothelial function in Type II diabetes. Endothelial production of nitric oxide (NO) has previously been linked to vascular health. Reactive hyperemia induces a significant increase in plasma nitrite, the proximal metabolite of NO, in healthy subjects, while diabetics have a lower and more variable level of response. Twenty type II diabetics and 20 controls (ages 46–70 years) were taken on a 1.5hr roadway traffic air pollution exposure as passengers. We analyzed plasma nitrite, as a measure of vascular function, using forearm ischemia to elicit a reactive hyperemic response before and after exposure to one ride with and one without filtration of the particle components of pollution. Control subjects displayed a significant increase in plasma nitrite levels during reactive hyperemia. This response was no longer present following exposure to traffic air pollution, but did not vary with whether or not the particle phase was filtered out. Diabetics did not display an increase in nitrite levels following reactive hyperemia. This response was not altered following pollution exposure. These data suggest that components of acute traffic pollution exposure diminish vascular reactivity in non-diabetic individuals. It also confirms that type II diabetics have a preexisting diminished ability to appropriately respond to a vascular challenge, and that traffic pollution exposure does not cause a further measureable acute change in plasma nitrite levels in Type II diabetics.     

Racial and Ethnic Cardiometabolic Risk Disparities in the Type 1 Diabetes Exchange Clinic Registry Cohort

ObjectiveTo determine whether individuals from a historically underrepresented racial group have a higher cardiometabolic risk than historically represented individuals with type 1 diabetes (T1D) considering socioeconomic deprivation.MethodsWe used the multivariable logistic and linear regression models to examine socioeconomic deprivation (upper 10th percentile) by race/ethnicity interaction for each cardiometabolic risk factor and cardiometabolic risk burden score, respectively, across 6320 zip code tabulation areas. We also determined the age-adjusted prevalence of low, moderate, and high cardiometabolic risks defined as 0, 1 to 2, and 3 or more risk factors for hypertension, obesity, dyslipidemia, and off-target glycemia for non-Hispanic White (n = 15 746), non-Hispanic Black (n = 1019), Hispanic (n = 1115), and other (n = 887), respectively.ResultsThe sample comprised 18 767 adolescents and adults with T1D. Those identifying as non-Hispanic Black were more likely to have a high cardiometabolic risk profile, including a 4.5-fold increase in the odds of off-target glycemia, a twofold increase in the odds of systolic hypertension, and 0.29 (unadjusted) and 0.46 (adjusted) increases in a higher cardiometabolic risk burden compared with non-Hispanic White individuals (P < .01). Those identifying as Hispanic had a 3.4-fold increase in the odds of off-target glycemia but were less likely to be overweight/obese or have systolic hypertension compared with non-Hispanic White. However, the lower likelihood of overweight/obesity and hypertension did not persist after considering covariates.ConclusionThere is a need to investigate additional determinants of racially/ethnically underrepresented cardiometabolic health, including structural racism and implicit bias in cardiometabolic care for individuals with T1D.     

Deaths and Medical Visits Attributable to Environmental Pollution in the United Arab Emirates

Background

This study estimates the potential health gains achievable in the United Arab Emirates (UAE) with improved controls on environmental pollution. The UAE is an emerging economy in which population health risks have shifted rapidly from infectious diseases to chronic conditions observed in developed nations. The UAE government commissioned this work as part of an environmental health strategic planning project intended to address this shift in the nature of the country’s disease burden.

Methods and Findings

We assessed the burden of disease attributable to six environmental exposure routes outdoor air, indoor air, drinking water, coastal water, occupational environments, and climate change. For every exposure route, we integrated UAE environmental monitoring and public health data in a spatially resolved Monte Carlo simulation model to estimate the annual disease burden attributable to selected pollutants. The assessment included the entire UAE population (4.5 million for the year of analysis). The study found that outdoor air pollution was the leading contributor to mortality, with 651 attributable deaths (95% confidence interval [CI] 143–1,440), or 7.3% of all deaths. Indoor air pollution and occupational exposures were the second and third leading contributors to mortality, with 153 (95% CI 85–216) and 46 attributable deaths (95% CI 26–72), respectively. The leading contributor to health-care facility visits was drinking water pollution, to which 46,600 (95% CI 15,300–61,400) health-care facility visits were attributed (about 15% of the visits for all the diseases considered in this study). Major study limitations included (1) a lack of information needed to translate health-care facility visits to quality-adjusted-life-year estimates and (2) insufficient spatial coverage of environmental data.

Conclusions

Based on international comparisons, the UAE’s environmental disease burden is low for all factors except outdoor air pollution. From a public health perspective, reducing pollutant emissions to outdoor air should be a high priority for the UAE’s environmental agencies.     

Evaluation of Bioelectrical Impedance Analysis for Identifying Overweight Individuals at Increased Cardiometabolic Risk: A Cross-Sectional Study

Objective

To investigate whether bioelectrical impedance analysis could be used to identify overweight individuals at increased cardiometabolic risk, defined as the presence of metabolic syndrome and/or diabetes.

Design and Methods

Cross-sectional study of a Scottish population including 1210 women and 788 men. The diagnostic performance of thresholds of percentage body fat measured by bioelectrical impedance analysis to identify people at increased cardiometabolic risk was assessed using receiver-operating characteristic curves. Odds ratios for increased cardiometabolic risk in body mass index categories associated with values above compared to below sex-specific percentage body fat thresholds with optimal diagnostic performance were calculated using multivariable logistic regression analyses. The validity of bioelectrical impedance analysis to measure percentage body fat in this population was tested by examining agreement between bioelectrical impedance analysis and dual-energy X-ray absorptiometry in a subgroup of individuals.

Results

Participants were aged 16-91 years and the optimal bioelectrical impedance analysis cut-points for percentage body fat for identifying people at increased cardiometabolic risk were 25.9% for men and 37.1% for women. Stratifying by these percentage body fat cut-points, the prevalence of increased cardiometabolic risk was 48% and 38% above the threshold and 24% and 19% below these thresholds for men and women, respectively. By comparison, stratifying by percentage body fat category had little impact on identifying increased cardiometabolic risk in normal weight and obese individuals. Fully adjusted odds ratios of being at increased cardiometabolic risk among overweight people with percentage body fat ≥25.9/37.1% compared with percentage body fat <25.9/37.1% as a reference were 1.93 (95% confidence interval: 1.20–3.10) for men and 1.79 (1.10–2.92) for women.

Conclusion

Percentage body fat measured using bioelectrical impedance analysis above a sex-specific threshold could be used in overweight people to identify individuals at increased cardiometabolic risk, who could benefit from risk factor management.     

Movement Discordance between Healthy and Non-Healthy US Adults

Introduction

Physical activity is known to significantly impact cardiometabolic health. Accelerometer data, as a measure of physical activity, can be used to objectively identify a disparity in movement (movement discordance) between healthy and unhealthy adults. The purpose of this study was to examine the Movement Discordance between healthy and unhealthy adults in a large US population sample.

Methods

Demographic, health and accelerometer data from the National Health and Nutrition Examination Study (NHANES) 2003–2004 and 2005–2006 cohorts were used for this study. Participants were classified as either having a “normal” or “abnormal” value for each cardiometabolic health parameter examined, based on published criteria. Linear regression analyses were performed to determine significance of each abnormal health parameter (risk factor) in its unique effect on the accelerometer counts, controlling for age and gender. Average accelerometer counts per minute (cpm) by gender and age categories were estimated separately for the groups of normal and abnormal cardiometabolic risk.

Results

Average cpm for those with healthy levels of each individual cardiometabolic health parameter range from 296 cpm (for C reactive protein) to 337 cpm (for waist circumference), while average cpm for those with abnormal levels of each individual cardiometabolic health parameter range from 216 cpm (for insulin) to 291 cpm (for LDL-cholesterol). After controlling for age and gender, waist circumference, HbA1c, Insulin, Homocysteine, and HDL-Cholesterol were the cardiometabolic health parameters that showed significant, unique and independent effects on cpm. Overall, individuals who have abnormal values for all significant cardiometabolic health parameters (“unhealthy”) averaged 267 cpm (SE = 15 cpm), while the healthy sample of this study averaged 428 cpm (SE = 10 cpm). The difference in cpm between the unhealthy and healthy groups is similar between males and females. Further, for both males and females, the cpm gap between unhealthy and healthy is largest in the 30s (males: 183 cpm; females 144 cpm) and lessens as age increases, with the lowest gap seen in those 80+ years (males, 81 cpm; females, 85 cpm).

Conclusion

This Movement Discordance between healthy and unhealthy adults represents a gap in movement that needs to be closed to improve the health of individuals with, or at risk for cardiometabolic disease.     

Body size phenotypes and inflammation in the Women's Health Initiative Observational Study

Individuals with "metabolically benign" obesity (obesity unaccompanied by hypertension, dyslipidemia, and diabetes) are not at elevated 10-year risk of cardiovascular disease (CVD) compared to normal weight individuals. It remains unclear whether these obese individuals or normal weight individuals with clustering of cardiometabolic factors display heightened immune activity. Therefore, we characterized levels of acute-phase reactants (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), white blood cell (WBC) count), adhesion molecules (E-selectin, vascular cell adhesion molecule-1), and coagulation products (fibrinogen, plasminogen activator inhibitor-1 (PAI-1)) among four body size phenotypes (normal weight with 0/1 vs. ≥2 metabolic syndrome components/diabetes and overweight/obesity with 0/1 vs. ≥2 metabolic syndrome components/diabetes) in cross-sectional analyses of 1,889 postmenopausal women from the Women's Health Initiative Observational Study (WHI-OS) nested case-control stroke study. Higher levels of all three inflammatory marker categories were found among women with overweight/obesity or ≥2 metabolic syndrome components or diabetes. Compared to normal weight women with 0 or 1 metabolic syndrome components, normal weight women with ≥2 metabolic syndrome components or diabetes were more likely to have ≥3 inflammatory markers in the top quartile (multivariate odds ratio (OR) 2.0, 95% confidence interval (CI): 1.3-3.0), as were overweight/obese women with 0 or 1 metabolic syndrome components (OR 2.3; 95% CI: 1.5-3.5). Overweight/obese women with ≥2 metabolic syndrome components or diabetes had the highest OR (OR 4.2; 95% CI: 2.9-5.9). Despite findings that metabolically benign obese individuals are not at increased 10-year risk of CVD compared to normal weight individuals, the current results suggest that overweight/obese women without clustering of cardiometabolic risk factors still possess abnormal levels of inflammatory markers.     

Cardiovascular Health Maintenance in Aging Individuals: The Implications for Transgender Men and Women on Hormone Therapy

ObjectiveTo review screening guidelines for cardiometabolic disease in aging patients and review literature describing the effect of hormone therapy (HT) on several key cardiometabolic processes to inform providers caring for older transgender individuals.MethodsA traditional literature review was performed using PubMed and Google Scholar databases.ResultsThe risk of cardiovascular disease increases with age. Exogenous sex hormones may interact with hormone-dependent metabolic pathways and affect some biochemical assays, but they do not necessarily impact clinical outcomes. While long-term HT is associated with an increased risk of some adverse cardiovascular outcomes, modern treatment regimens minimize this risk.ConclusionScreening for cardiometabolic derangements and risk reduction are important for all aging individuals. Currently, there is insufficient evidence to propose separate screening recommendations for transgender individuals on long-term HT. Aging transgender men and women should be monitored for cardiovascular disease in much the same way as their cisgender counterparts.     

Pleiotropy among Common Genetic Loci Identified for Cardiometabolic Disorders and C-Reactive Protein

Pleiotropic genetic variants have independent effects on different phenotypes. C-reactive protein (CRP) is associated with several cardiometabolic phenotypes. Shared genetic backgrounds may partially underlie these associations. We conducted a genome-wide analysis to identify the shared genetic background of inflammation and cardiometabolic phenotypes using published genome-wide association studies (GWAS). We also evaluated whether the pleiotropic effects of such loci were biological or mediated in nature. First, we examined whether 283 common variants identified for 10 cardiometabolic phenotypes in GWAS are associated with CRP level. Second, we tested whether 18 variants identified for serum CRP are associated with 10 cardiometabolic phenotypes. We used a Bonferroni corrected p-value of 1.1×10^-04 (0.05/463) as a threshold of significance. We evaluated the independent pleiotropic effect on both phenotypes using individual level data from the Women Genome Health Study. Evaluating the genetic overlap between inflammation and cardiometabolic phenotypes, we found 13 pleiotropic regions. Additional analyses showed that 6 regions (APOC1, HNF1A, IL6R, PPP1R3B, HNF4A and IL1F10) appeared to have a pleiotropic effect on CRP independent of the effects on the cardiometabolic phenotypes. These included loci where individuals carrying the risk allele for CRP encounter higher lipid levels and risk of type 2 diabetes. In addition, 5 regions (GCKR, PABPC4, BCL7B, FTO and TMEM18) had an effect on CRP largely mediated through the cardiometabolic phenotypes. In conclusion, our results show genetic pleiotropy among inflammation and cardiometabolic phenotypes. In addition to reverse causation, our data suggests that pleiotropic genetic variants partially underlie the association between CRP and cardiometabolic phenotypes.     

Soluble ST2 Associates with Diabetes but Not Established Cardiovascular Risk Factors: A New Inflammatory Pathway of Relevance to Diabetes?

Preliminary data mostly from animal models suggest the sST2/IL-33 pathway may have causal relevance for vascular disease and diabetes and thus point to a potential novel inflammatory link to cardiometabolic disease. However, the characterisation of sST2 levels in terms of metabolic or vascular risk in man is completely lacking. We sought to address this gap via a comprehensive analysis of risk factor and vascular correlates of sST2 in a cross-sectional study (pSoBid). We measured sST2 in plasma in 639 subjects and comprehensively related it to cardiovascular and diabetes risk factors and imaged atherosclerosis measures. Circulating sST2 levels increased with age, were lower in women and in highest earners. After adjusting for age and gender, sST2 levels associated strongly with markers of diabetes, including triglycerides [effect estimate (EE) per 1 standard deviation increase in sST2∶1.05 [95%CI 1.01,1.10]), liver function (alanine aminotransaminase [ALT] and γ-glutamyl transferase [GGT]: EE 1.05 [1.01,1.09] and 1.13 [1.07,1.19] respectively), glucose (1.02 [1.00,1.03]) and sICAM-1 (1.05 [1.02,1.07]). However, sST2 levels were not related to smoking, cholesterol, blood pressure, or atheroma (carotid intima media thickness, plaque presence). These results suggest that sST2 levels, in individuals largely without vascular disease, are related principally to markers associated with diabetes and ectopic fat and add support for a role of sST2 in diabetes. Further mechanistic studies determining how sST2 is linked to diabetes pathways may offer new insights into the inflammatory paradigm for type 2 diabetes.     

The relationship between night work,chronotype, and cardiometabolic risk factors in female hospital employees

Night work has emerged as a risk factor for many chronic diseases, including obesity, diabetes, and cardiovascular disease. While night work is linked to a number of cardiometabolic indices, few studies have explored how different parameters, such as cumulative night work and intensity of night work, may influence cardiometabolic risk. Fewer studies have also explored the relationship while considering chronotype, a potential modifier between shift-induced circadian disruption and cardiometabolic outcomes. The main objective is to determine the association between night work parameters and cardiometabolic risk factors. The secondary objective is to assess how the association between night work parameters and cardiometabolic risk factors differs by chronotype. A cross-sectional study was conducted with 325 full- and part-time female hospital employees (168 rotating night workers, 157 day workers). Night work status, cumulative night work duration, and night work intensity were determined through self-report, and cardiometabolic risk factors were assessed through clinical exams. Chronotype was determined using the Munich Chronotype Questionniare (MCTQ). Multiple linear regression was used to examine the association between night work parameters and cardiometabolic risk factors. Current night work, cumulative night work, and night work intensity are associated with a number of cardiometabolic indices, including higher waist circumference, body mass index, fasting glucose, blood pressure, and cardiometabolic risk score. When stratified by chronotype, night work parameters are associated with a number of cardiometabolic risk factors in the evening-oriented chronotype subgroup. There is no difference in cardiometabolic risk factors in morning-oriented chronotypes when comparing night work parameters, with the exception of LDL cholesterol. These results suggest that night work parameters are associated with cardiometabolic risk, and night workers with an evening-oriented chronotype may be more susceptible to the adverse cardiometabolic impacts of night work. Future studies should consider chronotype when examining the relationship between night work and cardiometabolic risk.     

Impact of cardiometabolic risk factor clusters on health-related quality of life in the U.S

Objective: Research has shown that risk factors for cardiovascular disease often cluster together, most notably overweight/obesity, diabetes, hyperlipidemia, and hypertension. The impact of cardiometabolic risk factor clusters on health‐related quality of life (HRQL) is not well understood. The purpose of this study was to examine and quantify the impact of cardiometabolic risk factor clusters on HRQL as measured by the SF (Short Form)‐12 Mental Component Scale (MCS‐12), SF‐12 Physical Component Scale (PCS‐12), EQ‐5D index (a generic quality of life index), and Visual Analogue Scale. Research Methods and Procedures: The Medical Expenditure Panel Survey is a nationally representative survey of the U.S. population. From 2000 to 2002, detailed information on sociodemographic characteristics and health conditions were collected for 36,697 adults with complete responses. Controlling for comorbidity and sociodemographic characteristics, this study estimated the marginal impact of cardiometabolic risk factor clusters on MCS‐12, PCS‐12, EQ‐5D index, and Visual Analogue Scale scores. Cardiometabolic risk factor clusters were defined as the presence of BMI ≥25 kg/m² and at least two of the following: diabetes, hyperlipidemia, and hypertension. Using BMI ≥30 kg/m² as the cut‐off was also examined. Results: The marginal impact of cardiometabolic risk factor clusters was highly statistically significant across all four HRQL measures and seemed to be clinically significant for all but the MCS‐12. The PCS‐12 showed a greater decrease in HRQL associated with physical function compared with mental function‐related domains of the MCS‐12. Discussion: Common cardiometabolic risk factor clusters such as overweight/obesity, diabetes, hypertension, and hyperlipidemia have a significant and negative impact on HRQL in the United States.     

Is Adipose Tissue a Reservoir for Viral Spread,Immune Activation,and Cytokine Amplification in Coronavirus Disease 2019?

Coronavirus disease 2019 (COVID‐19), the worst pandemic in more than a century, has claimed >125,000 lives worldwide to date. Emerging predictors for poor outcomes include advanced age, male sex, preexisting cardiovascular disease, and risk factors including hypertension, diabetes, and, more recently, obesity. This article posits new obesity‐driven predictors of poor COVID‐19 outcomes, over and above the more obvious extant risks associated with obesity, including cardiometabolic disease and hypoventilation syndrome in intensive care patients. This article also outlines a theoretical mechanistic framework whereby adipose tissue in individuals with obesity may act as a reservoir for more extensive viral spread, with increased shedding, immune activation, and cytokine amplification. This paper proposes studies to test this reservoir concept with a focus on specific cytokine pathways that might be amplified in individuals with obesity and COVID‐19. Finally, this paper underscores emerging therapeutic strategies that might benefit subsets of patients in which cytokine amplification is excessive and potentially fatal.     

Cardiometabolic Risk Factor Changes Observed in Diabetes Prevention Programs in US Settings: A Systematic Review and Meta-analysis

BackgroundThe Diabetes Prevention Program (DPP) study showed that weight loss in high-risk adults lowered diabetes incidence and cardiovascular disease risk. No prior analyses have aggregated weight and cardiometabolic risk factor changes observed in studies implementing DPP interventions in nonresearch settings in the United States.ConclusionsDPP lifestyle modification programs achieved clinically meaningful weight and cardiometabolic health improvements. Together, these data suggest that additional value is gained from these programs, reinforcing that they are likely very cost-effective.     

Immunological and cardiometabolic risk factors in the prediction of type 2 diabetes and coronary events: MONICA/KORA Augsburg case-cohort study

Background

This study compares inflammation-related biomarkers with established cardiometabolic risk factors in the prediction of incident type 2 diabetes and incident coronary events in a prospective case-cohort study within the population-based MONICA/KORA Augsburg cohort.

Methods and Findings

Analyses for type 2 diabetes are based on 436 individuals with and 1410 individuals without incident diabetes. Analyses for coronary events are based on 314 individuals with and 1659 individuals without incident coronary events. Mean follow-up times were almost 11 years. Areas under the receiver-operating characteristic curve (AUC), changes in Akaike''s information criterion (ΔAIC), integrated discrimination improvement (IDI) and net reclassification index (NRI) were calculated for different models. A basic model consisting of age, sex and survey predicted type 2 diabetes with an AUC of 0.690. Addition of 13 inflammation-related biomarkers (CRP, IL-6, IL-18, MIF, MCP-1/CCL2, IL-8/CXCL8, IP-10/CXCL10, adiponectin, leptin, RANTES/CCL5, TGF-β1, sE-selectin, sICAM-1; all measured in nonfasting serum) increased the AUC to 0.801, whereas addition of cardiometabolic risk factors (BMI, systolic blood pressure, ratio total/HDL-cholesterol, smoking, alcohol, physical activity, parental diabetes) increased the AUC to 0.803 (ΔAUC [95% CI] 0.111 [0.092–0.149] and 0.113 [0.093–0.149], respectively, compared to the basic model). The combination of all inflammation-related biomarkers and cardiometabolic risk factors yielded a further increase in AUC to 0.847 (ΔAUC [95% CI] 0.044 [0.028–0.066] compared to the cardiometabolic risk model). Corresponding AUCs for incident coronary events were 0.807, 0.825 (ΔAUC [95% CI] 0.018 [0.013–0.038] compared to the basic model), 0.845 (ΔAUC [95% CI] 0.038 [0.028–0.059] compared to the basic model) and 0.851 (ΔAUC [95% CI] 0.006 [0.003–0.021] compared to the cardiometabolic risk model), respectively.

Conclusions

Inclusion of multiple inflammation-related biomarkers into a basic model and into a model including cardiometabolic risk factors significantly improved the prediction of type 2 diabetes and coronary events, although the improvement was less pronounced for the latter endpoint.     

Human Exposure Pathways of Heavy Metals in a Lead-Zinc Mining Area,Jiangsu Province,China

Heavy metal pollution is becoming a serious issue in developing countries such as China, and the public is increasingly aware of its adverse health impacts in recent years. We assessed the potential health risks in a lead-zinc mining area and attempted to identify the key exposure pathways. We evaluated the spatial distributions of personal exposure using indigenous exposure factors and field monitoring results of water, soil, food, and indoor and outdoor air samples. The risks posed by 10 metals and the contribution of inhalation, ingestion and dermal contact pathways to these risks were estimated. Human hair samples were also analyzed to indicate the exposure level in the human body. Our results show that heavy metal pollution may pose high potential health risks to local residents, especially in the village closest to the mine (V1), mainly due to Pb, Cd and Hg. Correspondingly, the residents in V1 had higher Pb (8.14 mg/kg) levels in hair than those in the other two villages. Most of the estimated risks came from soil, the intake of self-produced vegetables and indoor air inhalation. This study highlights the importance of site-specific multipathway health risk assessments in studying heavy-metal exposures in China.     

Causal associations of sarcopenia-related traits with cardiometabolic disease and Alzheimer's disease and the mediating role of insulin resistance: A Mendelian randomization study

The causal influence of sarcopenia on cardiometabolic disease and Alzheimer's disease and whether and to what extent insulin resistance plays a mediating role therein were unclear. We performed two-step, two-sample Mendelian randomization applying genetic instruments of sarcopenia-related traits based on GWASs from the UK Biobank (up to 461,026 European participants) to examine their causal associations with six cardiometabolic diseases and Alzheimer's disease extracted from large-scale European descent GWASs with adjustment for body fat percentage and physical activity, and to assess proportions of the causal effects mediated by insulin resistance. Genetic instruments of insulin resistance were derived from the GWASs by Meta-Analyses of Glucose and Insulin-related traits Consortium and Global Lipids Genetics Consortium. Each 1-SD lower grip strength, appendicular lean mass (ALM) and whole-body lean mass (WBLM), as well as lower walking pace, were causally associated with higher risks of diabetes (odds ratio [OR] range: 1.20 [95% confidence interval: 1.10–1.32] for ALM to 2.30 [1.14–4.68] for walking pace), nonalcoholic fatty liver disease ([NAFLD], 1.33 [1.08–1.64] for ALM to 2.30 [1.02–5.18] for grip strength), hypertension (1.12 [1.05–1.20] for ALM to 4.43 [2.68–7.33] for walking pace), coronary heart disease ([CHD], 1.20 [1.13–1.27] for ALM to 2.73 [1.84–4.05] for walking pace), myocardial infarction ([MI], 1.18 [1.11–1.25] for ALM to 2.47 [1.63–3.73] for walking pace), small vessel stroke (1.25 [1.15–1.37] for ALM to 1.29 [1.10–1.52] for WBLM), and Alzheimer's disease (1.10 [1.05–1.15] for ALM to 1.28 [1.19–1.38] for WBLM). These causal associations were largely independent of body fat percentage and physical activity. Insulin resistance mediated 16%–34% of the effect of grip strength and 7%–28% of the effect of ALM on diabetes, NAFLD, hypertension, CHD, and MI. The direct effect of WBLM on diabetes diminished toward null with adjustment for insulin resistance. We found no evidence that insulin resistance was on the causal pathways from walking pace to the studied disease outcomes. Causal findings from the inverse-variance weighted method were validated by sensitivity analyses. These findings support improving sarcopenia-related traits as precautions against major cardiometabolic diseases and Alzheimer's disease, with particular emphasis on insulin resistance as a target in the intervention of sarcopenia-related cardiometabolic risk.     

Duration of obesity exposure between ages 10 and 40 years and its relationship with cardiometabolic disease risk factors: A cohort study

BackgroundIndividuals with obesity do not represent a homogeneous group in terms of cardiometabolic risk. Using 3 nationally representative British birth cohorts, we investigated whether the duration of obesity was related to heterogeneity in cardiometabolic risk.Methods and findingsWe used harmonised body mass index (BMI) and cardiometabolic disease risk factor data from 20,746 participants (49.1% male and 97.2% white British) enrolled in 3 British birth cohort studies: the 1946 National Survey of Health and Development (NSHD), the 1958 National Child Development Study (NCDS), and the 1970 British Cohort Study (BCS70). Within each cohort, individual life course BMI trajectories were created between 10 and 40 years of age, and from these, age of obesity onset, duration spent obese (range 0 to 30 years), and cumulative obesity severity were derived. Obesity duration was examined in relation to a number of cardiometabolic disease risk factors collected in mid-adulthood: systolic (SBP) and diastolic blood pressure (DBP), high-density-lipoprotein cholesterol (HDL-C), and glycated haemoglobin (HbA1c).A greater obesity duration was associated with worse values for all cardiometabolic disease risk factors. The strongest association with obesity duration was for HbA1c: HbA1c levels in those with obesity for <5 years were relatively higher by 5% (95% CI: 4, 6), compared with never obese, increasing to 20% (95% CI: 17, 23) higher in those with obesity for 20 to 30 years. When adjustment was made for obesity severity, the association with obesity duration was largely attenuated for SBP, DBP, and HDL-C. For HbA1c, however, the association with obesity duration persisted, independent of obesity severity. Due to pooling of 3 cohorts and thus the availability of only a limited number harmonised variables across cohorts, our models included adjustment for only a small number of potential confounding variables, meaning there is a possibility of residual confounding.ConclusionsGiven that the obesity epidemic is characterised by a much earlier onset of obesity and consequently a greater lifetime exposure, our findings suggest that health policy recommendations aimed at preventing early obesity onset, and therefore reducing lifetime exposure, may help reduce the risk of diabetes, independently of obesity severity. However, to test the robustness of our observed associations, triangulation of evidence from different epidemiological approaches (e.g., mendelian randomization and negative control studies) should be obtained.

Tom Norris and colleagues investigate how obesity duration and obesity severity throughout a person''s lifetime may affect cardiometabolic risk factors such as blood pressure, cholesterol, and glycated haemoglobin.     

HSP70 as a biomarker of the thin threshold between benefit and injury due to physical exercise when exposed to air pollution

Physical exercise has acute and chronic effects on inflammatory balance, metabolic regulation, and redox status. Exercise-induced adaptations are mediated by enhanced 70-kDa heat shock protein (HSP70) levels and an improved heat shock response (HSR). Therefore, exercise could be useful against disease conditions [obesity, diabetes mellitus (DM), and exposure to atmospheric pollutants] marked by an impaired HSR. However, exercise performed by obese or diabetic subjects under pollution conditions might also be dangerous at certain intensities. Intensity correlates with an increase in HSP70 levels during physical exercise until a critical point at which the effort becomes harmful and impairs the HSR. Establishing a unique biomarker able to indicate the exercise intensity on metabolism and cellular fatigue is essential to ensure adequate and safe exercise recommendations for individuals with obesity or DM who require exercise to improve their metabolic status and live in polluted regions. In this review, we examined the available evidence supporting our hypothesis that HSP70 could serve as a biomarker for determining the optimal exercise intensity for subjects with obesity or diabetes when exposed to air pollution and establishing the fine threshold between anti-inflammatory and pro-inflammatory exercise effects.     

Renin-angiotensin-aldosterone system and oxidative stress in cardiovascular insulin resistance

Hypertension commonly occurs in conjunction with insulin resistance and other components of the cardiometabolic syndrome. Insulin resistance plays a significant role in the relationship between hypertension, Type 2 diabetes mellitus, chronic kidney disease, and cardiovascular disease. There is accumulating evidence that insulin resistance occurs in cardiovascular and renal tissue as well as in classical metabolic tissues (i.e., skeletal muscle, liver, and adipose tissue). Activation of the renin-angiotensin-aldosterone system and subsequent elevations in angiotensin II and aldosterone, as seen in cardiometabolic syndrome, contribute to altered insulin/IGF-1 signaling pathways and reactive oxygen species formation to induce endothelial dysfunction and cardiovascular disease. This review examines currently understood mechanisms underlying the development of resistance to the metabolic actions of insulin in cardiovascular as well as skeletal muscle tissue.     

Nutritional modulation of cognitive function and mental health

The important role of diet in cardiometabolic health is generally well recognised; for mental health, it is not so well understood. However, lifestyle risk factors for poor physical health are the same risk factors for mental illness, including poor diet. This is reflected by the high level of poor physical health in people with mental illness. Mediterranean, whole food diets have been associated with reduced risk for chronic disease, but very little research has investigated their mental health benefits. We provide a model for the pathways by which food components provided by a Mediterranean-style diet can facilitate healthy brain function. We then review evidence for the role of selected nutrients/food components — antioxidants, omega-3 fatty acids and B vitamins — in the brain and, hence, modulation of cognitive function and mental health. Converging evidence indicates multiple pathways by which these nutrients can assist in brain function, drawing from studies investigating them in isolation. There is very little work done on synergistic actions of nutrients and whole diets, highlighting a need for human intervention studies investigating benefits of Mediterranean-style diets for mental, as well as cardiometabolic health.