Increase In Cardiometabolic Risk Research Articles

#715 Adiponectin / leptin ratio as an index to determine the risk of metabolic and rejection complications in patients after kidney transplantation

Abstract Background and Aims Adipose tissue, as an endocrine and paracrine organ, produces several hormones that are involved in the regulation of metabolic and inflammatory processes or immune system activity. While leptin is the main pro-inflammatory marker of adipose tissue, adiponectin is characterized by its anti-inflammatory effects. The adiponectin / leptin (A/L) ratio had been shown to correlate better with the occurrence of cardiometabolic risk factors than hormone concentrations alone. Results in the general population suggest that an A/L ratio > 1 can be considered normal, an A/L ratio of 0.5-1 indicates a moderate increase, and an A/L ration < 0.5 a high increase in cardiometabolic risk. The first aim of our study was to determine the risk of developing post-transplant diabetes mellitus (PTDM), prediabetes and other metabolic risk factors in relation to the A/L ratio in patients after kidney transplantation (KT). The second aim was to determine the risk of developing acute graft rejection in relation to the A/L ratio in patients after KT. Method A total of 104 patients were included in our prospective analysis after applying inclusion and exclusion criteria. Pre-transplantation and subsequently at 3, 6 and 12 months after KT, we recorded baseline characteristics of donors and recipients, including parameters characterizing graft function, metabolic (lipid profile, indices of glucose metabolism) and anthropometric parameters. At the same time, we examined serum adipocytokine concentrations (adiponectin, leptin) and calculated the A/L ratio. In the third month after KT, all patients underwent protocol graft biopsy and donor specific antibody (DSA) testing by Luminex method. Results We found that during the follow-up period, there was a significant increase in the A/L ratio in the control group (p = 0.0013) and, on the other hand, a significant decrease in the group who developed PTDM (p = 0.0003). Comparing the different subgroups divided on the A/L ratio one year after KT, we found that patients with an A/L < 0.5 were significantly longer in the dialysis program, had higher body mass index (BMI), waist circumference, worse graft function, and a higher prevalence of prediabetes and PTDM compared with those whose A/L ratio was > 1. Using logistic regression in multivariate analysis, we identified age at the time of KT [OR 1.0709, (p = 0.0337)], triglycerides level at 1 year after KT [OR 2.7735, (p = 0.446)] and A/L ratio < 0.5 [OR 3.1724, (p = 0.014)] as independent risk factors for the development of prediabetes and PTDM 1 year after KT. At the same time, after adjusting for differences in baseline donor and recipient characteristics, we identified the subgroup with an A/L ratio < 0.5 pre-transplant [HR 1.6126, (p = 0.0133)] and 3 months after KT [HR 1.3150, (p = 0.0172)] as an independent risk factor for the development of acute graft rejection. In the subsequent specification of the rejection episode, we found that A/L ratio < 0.5 pre-transplant [HR 2.2353, (p = 0.0357)] and 3 months after KT [HR 3.0954, (p = 0.0237)] is and independent risk factor for the occurrence of acute humoral rejection with DSA positivity. Conclusion In our study, we found that an A/L ratio < 0.5 is an independent risk factor for the development of prediabetes, PTDM 1 year after KT and acute humoral graft rejection with de novo DSA production in the third month after KT. This is the first study to investigate the correlation of the A/L ratio with the risk of developing metabolic and immunological complications in patients after KT.

Healthier Lifestyles Attenuated Association of Single or Mixture Exposure to Air Pollutants with Cardiometabolic Risk in Rural Chinese Adults.

There is little research on how long-term exposure to independent and multiple air pollutants changes cardiometabolic risk in adults. In addition, previous studies focused on only the effect of one or two lifestyles on cardiometabolic risk. The evidence on the interactive effects of the lifestyle score and exposure to independent and mixtures of air pollutants on cardiometabolic risk is lacking. A total of 33,638 rural residents were included in the cross-sectional study. The three-year average concentrations of air pollutants for participants were predicted by using a satellite-based prediction. The air pollution score was created to assess the combined exposure of four air pollutants (PM1, PM2.5, PM10, and NO2). A gender−age-specific cardiometabolic risk score was calculated. Multivariable-adjusted linear regression and quantile g-computation were used to investigate the associations between air pollutants and cardiometabolic risk. Interaction plots were applied to describe the interactive effects of air pollution and the healthy lifestyle score on cardiometabolic risk. Per interquartile range (IQR) unit increases in PM1, PM2.5, PM10, or NO2 were associated with 0.162 (95% CI: 0.091, 0.233), 0.473 (95% CI: 0.388, 0.559), 0.718 (95% CI: 0.627, 0.810), and 0.795 (95% CI: 0.691, 0.898) unit increases in cardiometabolic risk score (all p < 0.05), respectively. A 0.854 (95% CI: 0.768, 0.940) unit increase in cardiometabolic risk was associated with each IQR increase in air pollution score. Furthermore, the strengths of associations of PM1, PM2.5, PM10, NO2, and the air pollution score on cardiometabolic risk score were attenuated with the healthy lifestyle score increase. In addition, there was no statistical significance after the lifestyle score equal to four scores for the effect of PM1 on the cardiometabolic risk score. In conclusions, individual or joint air pollutants were associated with an increased cardiometabolic risk. Improving the healthy lifestyle may be an effective method to improve cardiometabolic health in highly polluted rural regions.

Subclinical hypothyroidism and metabolic syndrome: reasons for drug intervention

The high prevalence of metabolic syndrome (MS) and subclinical hypothyroidism (SHypo) creates danger of integral cardio-metabolic risk (CMR). A concept is being developed to increase thyroid-stimulating hormone (TSH) levels as a component of MS with the key role of insulin resistance (IR). To identify groups of active intervention, the definitions of SHypo with age and gender characteristics are analyzed. The results of randomized clinical trials showed a higher incidence of prediabetes and type 2 diabetes mellitus (T2DM) in SHypo, as well as positive associations of autoimmune thyroiditis (AIT) with components of MS, especially in postmenopausal women. The association of SHypo with a systemic inflammatory response is analyzed, which can determine an increase in cardio-metabolic risk. At the same time, most of the thyroid dysfunction and the components of MS are associated with insulin resistance.&#x0D; The feasibility of SHypo treating with levothyroxine is discussed: the threshold parameters of thyroid-stimulating hormone (TSH) are not determined for initiating treatment; in old age, due to a decrease in the need for thyroid hormones, an increase in the upper reference range of TSH is discussed; there is no evidence of a decrease in cardiovascular risk and mortality. In parallel, data have been accumulated on a decrease in TSH levels in overt and subclinical hypothyroidism in patients with MS and T2DM with metformin therapy. The gender effect of metformin on the activity of the hypothalamus-pituitary-thyroid axis was suggested, its new antihyperglycemic mechanism of action, including the activation of the AMP protein kinase (adenosine monophosphate (AMP) -activated protein kinase) in the pituitary gland, was revealed.&#x0D; It is possible that metformin is a promising therapeutic agent not only for patients with type 2 diabetes and thyroid disease, but also for MS and obesity. The multifaceted capabilities of metformin, including the correction of peripheral and central insulin resistance and a decrease in TSH levels in patients with SHypo, emphasizes an integrated approach to the prevention of CMR. The prolonged release form of metformin has several advantages: better tolerance, greater efficiency in the correction of IR, lipid and carbohydrate metabolism, additional indication - treatment of prediabetes, the possibility of prescribing for creatinine clearance up to 30 ml/min.

Artificial sweeteners impair endothelial vascular reactivity: Preliminary results in rodents

Background and aimsProspective epidemiological studies highlighted recently the link between artificial sweeteners (AS) consumption and the risk of developing cardiometabolic diseases. However, underlying mechanisms remain unknown. Thus, the aim of this preliminary study was to characterize, in a healthy rat population, the effect of chronic AS consumption on body composition and vascular function, an early marker for cardiovascular disease. Methods and resultsHealthy Wistar rats followed a 10-week standard diet including the consumption of water sweetened or not with a sucralose/acesulfame potassium solution at different concentrations: for moderate consumption at 1 and 2 mg.kg−1.day−1, respectively or high intake at 15 and 15 mg.kg−1.day−1 for both molecules (acceptable daily intake). Body fat composition has been evaluated and ex vivo aortic vasomotor function has been investigated with a pharmacological approach. ConclusionBoth groups of AS-treated rats showed a significant increase in subcutaneous and perirenal adipose tissue mass storage, without changes in total body mass. However, rats that have consumed AS at Acceptable Daily Intake (ADI) concentration revealed a significant vascular endothelial dysfunction compared to other groups. These results are interesting because they will help to better explain the observed increase in cardiometabolic risk.

Six-Year Incidence of Cardiometabolic Risk Factors in a Population-Based Cohort of Chinese Adults Followed From 2009 to 2015.

BackgroundChina faces a substantial burden from cardiometabolic diseases, but longitudinal studies on a wide range of cardiometabolic risk factors are limited. We examined the 6‐year incidence of 8 cardiometabolic risk factors in a diverse, population‐based cohort.Methods and ResultsIn the China Health and Nutrition Survey, anthropometry, blood pressure, and fasting blood samples were collected from 9621 adults (47.6% men) aged 18 to 99 years in 2009 who were followed into 2015. Using inverse probability weights to account for loss to follow‐up, we estimated the 6‐year incidence of 8 cardiometabolic risk factors and compared the incidence of each risk factor across age groups using inverse probability–weighted sex‐stratified logistic regression models. Incidence was noted for the following cardiometabolic risk factors during 2009–2015: hypertension (systolic/diastolic blood pressure ≥140/90 mm Hg; men: 29.2%; women: 24.9%), high waist circumference/height ratio (≥0.5; men: 42.4%; women: 43.8%), and high total to HDL (high‐density lipoprotein) cholesterol ratio (≥5; men: 17.0%; women: 14.5%). Older men and women (aged ≥65 years) had the highest incidence of hypertension. Incidence of high waist circumference/height ratio and high LDL (low‐density lipoprotein) cholesterol (≥130 mg/dL) was highest among older (aged ≥65 years) women, whereas incidence of overweight (body mass index ≥25) and high triglycerides (≥150 mg/dL) was highest among younger (aged 18–35 and 35–50 years) men.ConclusionsWe found increases in cardiometabolic risk among Chinese adults during this recent, short, 6‐year period that are higher than previous studies in China. The higher incidence of overweight and elevated dyslipidemia markers in younger versus older men portends an increasing burden of cardiometabolic diseases in China as the younger population ages.

EXERCISE TRAINING ASSOCIATED WITH DIETARY ADJUSTMENT INDUCES METABOLIC AND CARDIOVASCULAR BENEFITS IN HIGH‐FAT‐FED MENOPAUSE RATS

IntroductionConsidering the increase in cardiometabolic risk after menopause, and that diet and exercise training (ET) are the pillars of prevention/treatment strategies, the objective of this study was to evaluate the metabolic, hemodynamic and autonomic effects of exercise training in an experimental model of menopausal undergoing a high‐fat diet followed by dietary adjustment. Twenty female C57BL/6J mice (8 weeks aged), all oophorectomized (bilateral ovarian removal) divided into 4 experimental groups (n = 5) were used: sedentary submitted to a high‐fat diet (OSD), sedentary submitted to 4 weeks of high‐fat diet and 4 weeks of control diet (OSRa), trained submitted to a high‐fat diet (OTD), trained submitted to 4 weeks of high‐fat diet and 4 weeks of control diet (OTRa). Oophorectomy was performed at the end of the 4th week of the protocol. Fasting glycemia and oral glucose tolerance were evaluated. ET had duration of 4 weeks (6th to 9th week of protocol, 5 days/week, 1 hour/day, intensity 50–70% of the maximum treadmill test). At the end of the protocol, the animals were cannulated for direct recording of arterial pressure (AP), after which baroreflex sensitivity and cardiovascular autonomic modulation were analyzed.RESULTSDietary adjustment promoted a reduction in glycemia and a better glucose tolerance, associated with reduction in cardiac sympathetic modulation (LF‐PI: OSD: 0.54±0.02; OSRa: 0.37±0.06; OTD: 3.0±0.02, OTRa: 0.19±0.02 ms2) and vascular (LF‐SAP: OSD: 11.3±1.7, OSRa: 3.6±0.9, OTD: 1.6±0.2; OTR:3.0±0.5mmHg2). ET, with or without dietary adjustment, increased physical capacity, reduced heart rate, improved baroreflex sensitivity, increased cardiac parasympathetic modulation (HF‐PI: OSD: 0.47±0.04, OSRa: 0,63±0.07, OTD: 0.86±0.02, OTRa: 0.75±0.07 ms2) and reduction of cardiac and vascular sympathetic modulation. However, only the association of ET with dietary adjustment was able to promote reduction in body weight, glycemia, improvement in glucose tolerance, reduction in blood pressure (mean AP: OSD: 123±2.1, OSRa: 114±0.8; OTD: 120±1.4; OTR: 110±4.0 mmHg), and further increase in parasympathetic modulation. Thus, the association of ET with dietary adjustment may be considered an important behavior for the management of cardiovascular risk in the association of obesity with ovarian deprivation.Support or Funding InformationCoordenação de Aperfeiçoamento de Pessoal de Nível Superior ‐ Brazil (CAPES) ‐ Funding Code: 001.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Adiponectin-leptin Ratio is a Functional Biomarker of Adipose Tissue Inflammation

Obesity favors the development of cardiometabolic alterations such as type 2 diabetes (T2D) and the metabolic syndrome (MS). Obesity and the MS are distinguished by an increase in circulating leptin concentrations, in parallel to a drop in the levels of adiponectin. Consequently, the Adpn/Lep ratio has been suggested as a maker of dysfunctional adipose tissue. We aimed to investigate in humans (n = 292) the reliability of the Adpn/Lep ratio as a biomarker of adipose tissue dysfunction. We considered that an Adpn/Lep ratio of ≥1.0 can be considered normal, a ratio of ≥0.5 <1.0 suggests moderate-medium increased risk, and a ratio of <0.5 indicates a severe increase in cardiometabolic risk. Using these cut-offs, 5%, 54% and 48% of the lean, normoglycemic and without-MS subjects, respectively, fall within the group with an Adpn/Lep ratio below 0.5; while 89%, 86% and 90% of the obese, with T2D and with MS patients fall within the same group (p < 0.001). A significant negative correlation (r = −0.21, p = 0.005) between the Adpn/Lep ratio and serum amyloid A (SAA) concentrations, a marker of adipose tissue dysfunction, was found. We concluded that the Adpn/Lep ratio is a good indicator of a dysfunctional adipose tissue that may be a useful estimator of obesity- and MS-associated cardiometabolic risk, allowing the identification of a higher number of subjects at risk.

Body fat distribution: the answer to the apparent paradox of obesity in cardiology?

Today, despite all the measures taken, cardiovascular diseases remain the main cause of temporary invalidization, disability and mortality. Obesity is a major risk factor of cardiovascular diseases and complications from them. However, not all fat depots have the same proinflammatory, paracrine and metabolic activity. Recent studies have shown that the accumulation of visceral fat, and not subcutaneous fat, is associated with an increase in cardiometabolic risk. At the same time, there is evidence that an increase in the area of visceral fat is a protective mechanism against lipotoxicity. The purpose of this review is to discuss current literature data reflecting the characteristics of the visceral, epicardial and perivascular fat depots, and also their association with cardiovascular diseases.

East Meets West: The Increasing Incidence of Inflammatory Bowel Disease in Asia as a Paradigm for Environmental Effects on the Pathogenesis of Immune-Mediated Disease

East Meets West: The Increasing Incidence of Inflammatory Bowel Disease in Asia as a Paradigm for Environmental Effects on the Pathogenesis of Immune-Mediated Disease

Longitudinal Changes in Body Fat and Its Distribution in Relation to Cardiometabolic Risk in Black South African Women.

Ethnic differences in body composition and cardiometabolic risk have been reported in cross-sectional studies. This study aimed to investigate changes in body composition over 5.5 years, and its association with cardiometabolic risk in premenopausal black South African (SA) women. Changes in body composition and body fat distribution (dual-energy x-ray absorptiometry and computerized tomography), fasting glucose, insulin, and lipid concentrations, were measured in 63 black SA women at baseline (age: 27 ± 8 years), and 5.5 years later. Body weight and fat mass (FM) increased by 6.9 ± 9.9 kg and 4.3 ± 6.9 kg, respectively, over the 5.5 years with a relative (%FM) increase in central and decrease in peripheral FM (all P < 0.05). Fasting glucose and lipid concentrations (except HDL-cholesterol) increased over the follow-up period (all P < 0.05). Both baseline and changes in body fat distribution were associated with cardiometabolic risk. Independent of baseline age, FM and insulin sensitivity, baseline trunk:leg was associated with reduced insulin sensitivity at follow-up (Matsuda index; β = -0.41, P = 0.002). Increasing trunk:gynoid ratio was associated with higher plasma insulin levels (β = 0.31, P = 0.023) and reduced insulin sensitivity (Matsuda index; β = -0.52, P < 0.001) at follow-up. Weight gain in free-living black SA women over 5.5 years was associated with a centralization of fat mass, which predicted an increase in cardiometabolic risk.

Perceived health status and cardiometabolic risk among a sample of youth in Mexico.

To examine differences in self-reported perceived mental and physical health status, as well as known cardiometabolic risk factors in a sample of normal weight, overweight, and obese Mexican youths. Cross-sectional analysis of 164 youths aged 11-18 years recruited in Cuernavaca, Mexico. Participants completed a self-administered questionnaire that included measures of generic and weight-specific quality of life, perceived health, physical function, depressive symptoms, and body shape satisfaction. Height, weight, and waist circumference were measured, and body mass index (BMI) was determined. Fasting blood samples from participants yielded levels of glucose, triglycerides, and cholesterol (total, HDL, and LDL). Nearly 50 % of participants were female, 21 % had a normal BMI, 39 % were overweight, and 40 % were obese. Obese youths reported significantly lower measures of perceived health status (PHS) and showed an increase in cardiometabolic risk, compared with normal weight youths. Physical functioning, generic and weight-specific QoL were inversely associated with BMI, waist circumference, and glucose. Depressive symptoms were positively correlated with BMI, waist circumference, glucose levels, and HDL cholesterol. No correlation was found between PHS and cardiometabolic risk measures after controlling for BMI. In this sample of Mexican youths, obesity was associated with a significantly lower PHS and increased cardiometabolic risk.

Effects of (−)-epicatechin on a diet-induced rat model of cardiometabolic risk factors

Overweight and obesity have been associated with increase in cardiometabolic risk. Therapeutics include lifestyle changes and/or pharmacologic agents. However, such interventions are often limited by poor compliance and/or significant side effects. The consumption of certain dietary products, such as cocoa, exerts positive effects on cardiometabolic risk factors. (−)-Epicatechin (EPI), the most abundant flavonoid in cacao has been reported to replicate such effects. However its mechanisms of action have not been fully elucidated.In a rat model of high-fat diet-induced obesity and its associated crdiometabolic risk factors, we administered 1mg/kg of EPI, by gavage, for 2 weeks. Endpoints included weight-gain, glycemia, triglyceridemia, and systolic blood pressure. We also assessed food intake and fecal excretion. Mitochondrial function and structure related proteins were measured by Westerns.Obesity, hyperglycemia, hypertriglyceridemia, and systolic hypertension were developed after the administration of the high-fat diet for five weeks. EPI significantly decreased the rate of weight gain, glycemia and hypertriglyceridemia. The ratio between energy intake and excretion was not significantly modified by treatment. EPI restored the obesity-induced decreases in the levels of skeletal muscle and abdominal tissue sirtuins (SIRTs), peroxisome proliferator-activated receptor coactivator (PGC-1α), mitofilin, transcription factor A mitochondrial (TFAM), uncoupling protein 1 (UCP1), and deiodinase.EPI treatment yielded beneficial effects on high fat diet-induced endpoints thus may be considered as a potential agent for the treatment of obesity and its cardiometabolic associated abnormalities. Mechanism of action may be attributed to the modulation of cellular/mitochondrial function, thus improving overall metabolism.

Acute Sedentary Behaviour and Markers of Cardiometabolic Risk: A Systematic Review of Intervention Studies

North Americans spend half their waking hours engaging in sedentary behaviour. Although several recent interventions suggest that short bouts of uninterrupted sedentary behaviour may result in acute increases in cardiometabolic risk, this literature has not been reviewed systematically. This study performed a systematic review of the impact of uninterrupted sedentary behaviour lasting ≤7 days on markers of cardiometabolic risk (insulin sensitivity, glucose tolerance, and fasting insulin, glucose, and lipid levels) in humans. Interventions were identified through systematic searches of Medline and Embase and screened by 2 independent reviewers. A total of 25 interventions were identified that examined the impact of imposed sedentary behaviour on biomarkers of interest. The majority of these studies focused on healthy young men, with very little identified research on females or other age groups. We found consistent, moderate quality evidence that uninterrupted sedentary behaviour ≤7 days results in moderate and deleterious changes in insulin sensitivity, glucose tolerance, and plasma triglyceride levels. In contrast, there is inconsistent, very low-quality evidence linking uninterrupted sedentary behaviour with changes in insulin, glucose, and HDL- and LDL-cholesterol levels. These findings suggest that uninterrupted bouts of sedentary behaviour should be avoided in order to prevent or attenuate transient increases in metabolic risk.

Understanding obesity in the older person: prevalence and risk factors

District nurses deal with many overweight and obese clients on their caseloads. Many of these people have various co-morbities; their weight issues are often glossed over, prioritizing more pressing clinical issues. This however is a mistake, in this article the issue of obesity in the elderly is mapped out. It starts with looking at the reasons behind the epidemic and looking at individual factors. The elderly suffer from sarcopenia as a result of ageing which leads to changes in body morphology. If not tackled early, such changes lead to considerable increases in cardiometabolic risk. Widespread increases in BMI have been shown to promote CHD, hypertension, type 2 diabetes and certain types of cancers. Clinical depression can be a manifestation of obesity. An overview of the prevalence and non-conservative clinical management is given.