Development Of Cardiometabolic Diseases Research Articles

Maternal androgen excess increases the risk of pre-diabetes mellitus in male offspring in later life: a long-term population-based follow-up study.

Prenatal androgen exposure could be a source of early programming, leading to the development of cardiometabolic diseases in later life. In this study, we aimed to examine cardiometabolic disturbances in males exposed to maternal androgen excess during their prenatal life. In this prospective population-based study, 409 male offspring with maternal hyperandrogenism (MHA), and 954 male offspring without MHA, as controls, were included. Both groups of male offspring were followed from the baseline to the date of the incidence of events, censoring, or end of the study period, whichever came first. Age-scaled unadjusted and adjusted Cox regression models were applied to assess the hazard ratios (HR) and 95% confidence intervals (CIs) for the association between MHA with pre-diabetes mellitus (Pre-DM), type 2 diabetes mellitus (T2DM), pre-hypertension (Pre-HTN), hypertension (HTN), dyslipidemia, overweight, and obesity in the offspring of both groups. Statistical analysis was performed using the STATA software package; the significance level was set at P < 0.05. A higher risk of Pre-DM (adjusted HR: 1.46 (1.20, 1.78)) was observed in male offspring with MHA after adjustment for potential confounders, including body mass index, education, and physical activity. However, no significant differences were observed in the risk of T2DM, Pre-HTN, HTN, dyslipidemia, overweight, and obesity in males with MHA compared to controls in both the unadjusted and adjusted models. Maternal androgen excess increases the risk of Pre-DM in male offspring in later life. More longitudinal studies with long enough follow-up are needed to clarify the effects of MHA on the cardiometabolic risk factors of male offspring in later life.

Benefits of Biotics for Cardiovascular Diseases.

Cardiovascular diseases are the main cause of death in many countries, and the better prevention and prediction of these diseases would be of great importance for individuals and society. Nutrition, the gut microbiota, and metabolism have raised much interest in the field of cardiovascular disease research in the search for the main mechanisms that promote cardiovascular diseases. Understanding the interactions between dietary nutrient intake and the gut microbiota-mediated metabolism may provide clinical insight in order to identify individuals at risk of cardiometabolic disease progression, as well as other potential therapeutic targets to mitigate the risk of cardiometabolic disease progression. The development of cardiometabolic diseases can be modulated by specific beneficial metabolites derived from bacteria. Therefore, it is very important to investigate the impact of these metabolites on human health and the possibilities of modulating their production with dietary supplements called biotics.

Pregnancy Complications and Long-Term Mortality in a Diverse Cohort.

Pregnancy complications are associated with increased risk of development of cardiometabolic diseases and earlier mortality. However, much of the previous research has been limited to White pregnant participants. We aimed to investigate pregnancy complications in association with total and cause-specific mortality in a racially diverse cohort and evaluate whether associations differ between Black and White pregnant participants. The Collaborative Perinatal Project was a prospective cohort study of 48 197 pregnant participants at 12 US clinical centers (1959-1966). The Collaborative Perinatal Project Mortality Linkage Study ascertained participants' vital status through 2016 with linkage to the National Death Index and Social Security Death Master File. Adjusted hazard ratios (aHRs) for underlying all-cause and cause-specific mortality were estimated for preterm delivery (PTD), hypertensive disorders of pregnancy, and gestational diabetes/impaired glucose tolerance (GDM/IGT) using Cox models adjusted for age, prepregnancy body mass index, smoking, race and ethnicity, previous pregnancies, marital status, income, education, previous medical conditions, site, and year. Among 46 551 participants, 45% (21 107 of 46 551) were Black, and 46% (21 502 of 46 551) were White. The median time between the index pregnancy and death/censoring was 52 years (interquartile range, 45-54). Mortality was higher among Black (8714 of 21 107 [41%]) compared with White (8019 of 21 502 [37%]) participants. Overall, 15% (6753 of 43 969) of participants had PTD, 5% (2155 of 45 897) had hypertensive disorders of pregnancy, and 1% (540 of 45 890) had GDM/IGT. PTD incidence was higher in Black (4145 of 20 288 [20%]) compared with White (1941 of 19 963 [10%]) participants. The following were associated with all-cause mortality: preterm spontaneous labor (aHR, 1.07 [95% CI, 1.03-1.1]); preterm premature rupture of membranes (aHR, 1.23 [1.05-1.44]); preterm induced labor (aHR, 1.31 [1.03-1.66]); preterm prelabor cesarean delivery (aHR, 2.09 [1.75-2.48]) compared with full-term delivery; gestational hypertension (aHR, 1.09 [0.97-1.22]); preeclampsia or eclampsia (aHR, 1.14 [0.99-1.32]) and superimposed preeclampsia or eclampsia (aHR, 1.32 [1.20-1.46]) compared with normotensive; and GDM/IGT (aHR, 1.14 [1.00-1.30]) compared with normoglycemic. P values for effect modification between Black and White participants for PTD, hypertensive disorders of pregnancy, and GDM/IGT were 0.009, 0.05, and 0.92, respectively. Preterm induced labor was associated with greater mortality risk among Black (aHR, 1.64 [1.10-2.46]) compared with White (aHR, 1.29 [0.97-1.73]) participants, while preterm prelabor cesarean delivery was higher in White (aHR, 2.34 [1.90-2.90]) compared with Black (aHR, 1.40 [1.00-1.96]) participants. In this large, diverse US cohort, pregnancy complications were associated with higher mortality nearly 50 years later. Higher incidence of some complications in Black individuals and differential associations with mortality risk suggest that disparities in pregnancy health may have life-long implications for earlier mortality.

Association between childhood BMI trajectories and cardiometabolic risk and mental health problems at the age of 13 years: the cohort STudy of Adolescence Resilience and Stress (STARS)

BackgroundResearch on BMI trajectories has been focused mainly on childhood and adolescence, missing birth and infancy, which are also relevant in the development of cardiometabolic disease in adulthood. We aimed to identify trajectories of BMI from birth throughout childhood, and to examine whether BMI trajectories predict health outcomes at the age of 13 years; and, if so, whether differences exist among trajectories regarding timeframes during which BMI in early life influences health outcomes. MethodsParticipants recruited from schools in the Västra Götaland region of Sweden completed questionnaires of perceived stress and psychosomatic symptoms and were examined for the following cardiometabolic risk factors: BMI, waist circumference, systolic blood pressure, pulse-wave velocity, and white blood cell counts. We collected ten retrospective measures of weight and height, from birth to the age of 12 years. Participants with at least five measures (at birth, one at age 6–18 months, two at age 2–8 years, and one at age 10–13 years) were included in the analyses. We used group-based trajectory modelling to identify BMI trajectories, ANOVA to compare different trajectories, and linear regression to assess associations. FindingsWe recruited 1902 participants (829 [44%] boys and 1073 [56%] girls, median age 13·6 years (IQR 13·3–13·8). We identified and named three BMI trajectories, and categorised participants accordingly: normal gain (847 [44%] participants), moderate gain (815 [43%] participants), and excessive gain (240 [13%] participants). Differences distinguishing these trajectories were established before the age of 2 years. After adjustments for sex, age, migrant background, and parental income, respondents with excessive gain had a higher waist circumference (mean difference 19·2 cm [95% CI 18·4–20·0]), higher systolic blood pressure (mean difference 3·6 mm Hg [95% CI 2·4–4·4]), more white blood cells (mean difference 0·7 × 10⁹ cells per L [95% CI 0·4–0·9]), and higher stress scores (mean difference 1·1 [95% CI 0·2–1·9]), but similar pulse-wave velocity compared with adolescents with normal gain. Higher waist circumference (mean difference 6·4 cm [95% CI 5·8–6·9]), higher systolic blood pressure (mean difference 1·8 mm Hg [95% CI 1·0–2·5]), and a higher stress score (mean difference 0·7 [95% CI 0·1–1·2]) were also found in adolescents with moderate gain, compared with adolescents with normal gain. Regarding timeframes, we observed that a significant positive correlation of early life BMI with systolic blood pressure started approximately at the age 6 years for participants with excessive gain, much earlier than for participants with normal gain and moderate gain, for which it started at the age of 12 years. For waist circumference, white blood cell counts, stress, and psychosomatic symptoms, the timeframes were similar across the three BMI trajectories. InterpretationExcessive gain BMI trajectory from birth can predict both cardiometabolic risk and stress and psychosomatic symptoms in adolescents before the age of 13 years. FundingSwedish Research Council (grant reference 2014-10086).

Exploring the Role of Dairy Products In Sleep Quality: From Population Studies to Mechanistic Evaluations.

Poor sleep quality and insufficient sleep affect a large portion of the population. This is concerning given increasing evidence that poor sleep health is a behavioral risk factor for the development of cardiometabolic diseases. A healthy diet is associated with a plethora of favorable health outcomes, and emerging research now highlights diet as a potential determinant of sleep health that could be leveraged to improve sleep quality. Dairy products are notably rich in tryptophan (Trp), a key substrate for serotonin and melatonin production, which are instrumental for initiating and maintaining sleep. Furthermore, dairy products provide a range of micronutrients that serve as cofactors in the synthesis of melatonin from Trp, which could contribute to sleep-promoting effects. In this review, we evaluate population studies and clinical trials to examine a possible link between dairy consumption and sleep. Available epidemiologic studies illustrate positive associations between dairy intake and sleep outcomes. Moreover, some intervention studies support a causal effect of dairy intake on sleep. Given these data, we discuss potential mechanisms, invite additional clinical research on this topic, and provide insights on how limitations of current studies can be addressed in future trials.

Abstract P340: Development and Delivery of an Effective 16-week HealthEYou Program to Mitigate Metabolic Disease Risk Factors

Introduction: Metabolic syndrome (MetS) is a growing concern in the U.S and around the world. MetS is a cluster of disease risk factors including hypertension, hyperlipidemia, hyperglycemia, and obesity increasing the risk of cardiometabolic disease development. Purpose: The purpose of this study was to assess the efficacy of a 16-week nutrition and physical activity education program (HealthEYou) in mediating metabolic risk factors associated with MetS. Methods: This was a two phase study including phase 1) the use of a person-based approach and community needs assessment to develop a nutrition and physical activity education program, and 2) delivery of the 16-week workplace education program and assessment of its effectiveness. In phase 1, a survey and focus groups were used to assess the needs of the target population to develop the 16-week education program. Twenty-six participants (96% female; age: 50.1±9.2 yrs; BMI: 31.2±5.3 kg/m2) enrolled in the HealthEYou program. At baseline, 8- and 16-weeks participants completed assessments including blood pressure, body composition via Dual-energy X-ray absorptiometry (DXA) and waist circumference, 6-minute walk test, handgrip strength test, dietary intake via the Automated Self-Administered 24-hour (ASA-24) dietary assessment tool, and quality of life questionnaire. In addition, blood was drawn to assess metabolic disease risk markers (total cholesterol, glucose and hemoglobin A1c (HbA1c)). The education program consisted of 8-weeks in-person weekly interactive group (60 min) and individual goal setting (15 min) sessions and 8-weeks of weekly newsletters and two individual goal setting sessions. Results: Data was analyzed using repeated measures analysis of variance. The prevalence of MetS among the participants decreased significantly from 41.7% at baseline to 15.8% after completion of the program. There was a significant decrease from baseline compared to after 16-weeks in fat mass (36.8±10.5 kg and 34.4 ±10.47 kg, p=0.003) and HbA1c (5.36±0.40% and 5.12±0.37%, p=0.001). In addition, significant improvements in distance walked, handgrip strength, caloric intake and quality of life (p&lt;0.05) were also observed. However, no significant changes (p&gt;0.05) in total cholesterol, fasting blood glucose or systolic and diastolic blood pressure were observed at 16-weeks compared to baseline measures. Conclusion: In conclusion, the use of a person-based approach and community needs assessment was beneficial to the development of a 16-week nutrition and physical activity education program. Participants who completed the 16-week program had significant improvements in a number of metabolic risk factors. In addition, the physiological improvements corresponded with improvements in dietary intake and fitness levels, suggesting participants made positive lifestyle changes.

The Role of Adiponectin during Pregnancy and Gestational Diabetes.

Pregnancy involves a range of metabolic adaptations to supply adequate energy for fetal growth and development. Gestational diabetes (GDM) is defined as hyperglycemia with first onset during pregnancy. GDM is a recognized risk factor for both pregnancy complications and long-term maternal and offspring risk of cardiometabolic disease development. While pregnancy changes maternal metabolism, GDM can be viewed as a maladaptation by maternal systems to pregnancy, which may include mechanisms such as insufficient insulin secretion, dysregulated hepatic glucose output, mitochondrial dysfunction and lipotoxicity. Adiponectin is an adipose-tissue-derived adipokine that circulates in the body and regulates a diverse range of physiologic mechanisms including energy metabolism and insulin sensitivity. In pregnant women, circulating adiponectin levels decrease correspondingly with insulin sensitivity, and adiponectin levels are low in GDM. In this review, we summarize the current state of knowledge about metabolic adaptations to pregnancy and the role of adiponectin in these processes, with a focus on GDM. Recent studies from rodent model systems have clarified that adiponectin deficiency during pregnancy contributes to GDM development. The upregulation of adiponectin alleviates hyperglycemia in pregnant mice, although much remains to be understood for adiponectin to be utilized clinically for GDM.

The Current Understanding of Fathers Influence on Cardiometabolic Risk Factor Development in Adolescence: A Brief Review

The influence that parents and caregivers have on childhood development is understood and validated. Current research is focused on psychological, social, physical, and spiritual health. Though, in recent years, the early development of cardiometabolic diseases has increased among younger individuals at earlier time periods. The full extent behind the rapid development of these diseases remains unclear. Therefore, the specific influence that each parent or guardian potentially has on future cardiometabolic health development in children and adolescence is an area of growing interest. Significant research has been performed to conclude that the mother has a crucial role in proper childhood development. However, there is limited amount of published research that has isolated the specific role that fathers have on future physiological health outcomes in relation to cardiometabolic health. Thus, the focus of this brief literature review was to ascertain the current influence that a paternal parent has on cardiometabolic health development throughout childhood and adolescence. The results of the review are limited to studies focused on physical growth, nutrition, metabolism, and cardiovascular disease. For many of the studies, the father’s role was assessed as a secondary or tertiary variable, and not as a primary factor or outcome. Based on the scarce amount of literature involving the father’s role in influencing cardiometabolic health outcomes, a clear consensus cannot be fully ascertained, and future research into this area is severely needed.&#x0D;

Abstract 11758: Sex Differences in the Associations Between Uric Acid and Incidence of Hypertension, Diabetes, and Chronic Kidney Disease in a Healthy Japanese Population

Introduction: Uric acid (UA) has been linked to the development of cardiometabolic diseases. However, the effects of UA levels by sex have not been reported. Hypothesis: We hypothesized that UA plays a critical role in the development of hypertension, diabetes, and chronic kidney disease (CKD) in Japanese men and women who are apparently healthy at baseline. Methods: This retrospective cohort study included individuals who participated in a health checkup at the Kagoshima Kouseiren Hospital from October 2008 to April 2019 who had a 5-year follow-up. We excluded participants with hypertension, diabetes, dyslipidemia, obesity, estimated glomerular filtration rate (eGFR) &lt;60 ml/min/1.73m2, history of gout, hyperuricemia medication, and missing data at baseline. Uric acid levels were divided into quartiles as follows: men: 1st quartile UA &lt; 4.8 mg/dL, 2nd quartile 4.9-5.6 mg/dL, 3rd quartile 5.7-6.4 mg/dL, and 4th quartile UA &gt; 6.5 mg/dL; women: 1st quartile UA &lt; 3.4 mg/dL, 2nd quartile 3.5-4.0 mg/dL, 3rd quartile 4.1-4.7 mg/dL, and 4th quartile UA &gt; 4.8 mg/dL. To assess the association between baseline UA levels and the development of hypertension, diabetes, and CKD, we performed a multivariable logistic regression analysis adjusted for age, body mass index, systolic blood pressure, diastolic blood pressure, current smoking, alcohol consumption, exercise habit, serum triglyceride, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, fasting plasma glucose, and eGFR by sex. Results: In total, 21,514 participants (age, 52.9±10.9 years; men, 39.8%), were enrolled. In men, the OR and 95% CI for the fourth to first quartile was associated with increased risk for hypertension (OR, 1.35; 95% CI, 1.13-1.62, P=0.0011), and CKD (OR, 1.42; 95% CI, 1.04-1.95, P=0.0287), and inversely related with diabetes (OR, 0.60; 95% CI, 0.39-0.93, P=0.0221). In women, the OR and 95% CI for the fourth to first quartile showed no association with neither hypertension (OR, 1.14; 95% CI, 0.95-1.36, P=0.1541), diabetes (OR, 0.97; 95% CI, 0.53-1.77, P=0.9271), nor CKD (OR, 1.26; 95% CI, 0.97-1.65, P=0.0828). Conclusion: Elevated serum UA indicates the risk of future hypertension and CKD, and an inverse relation with diabetes in apparently healthy Japanese men.

The role of oestrogen in determining sexual dimorphism in energy balance.

Energy balance is determined by caloric intake and the rate at which energy is expended, with the latter comprising resting energy expenditure, physical activity and adaptive thermogenesis. The regulation of both energy intake and expenditure exhibits clear sexual dimorphism, with young women being relatively protected against weight gain and the development of cardiometabolic diseases. Preclinical studies have indicated that females are more sensitive to the satiety effects of leptin and insulin compared to males. Furthermore, females have greater thermogenic activity than males, whereas resting energy expenditure is generally higher in males than females. In addition to this, in post-menopausal women, the decline in sex steroid concentration, particularly in oestrogen, is associated with a shift in the distribution of adipose tissue and overall increased propensity to gain weight. Oestrogens are known to regulate energy balance and weight homeostasis via effects on both food intake and energy expenditure. Indeed, 17β-oestradiol treatment increases melanocortin signalling in the hypothalamus to cause satiety. Furthermore, oestrogenic action at the ventromedial hypothalamus has been linked with increased energy expenditure in female mice. We propose that oestrogen action on energy balance is multi-faceted and is fundamental to determining sexual dimorphism in weight control. Furthermore, evidence suggests that the decline in oestrogen levels leads to increased risk of weight gain and development of cardiometabolic disease in women across the menopausal transition.

Slower Growth during Lactation Rescues Early Cardiovascular and Adipose Tissue Hypertrophy Induced by Fetal Undernutrition in Rats.

Low birth weight (LBW) and accelerated growth during lactation are associated with cardiometabolic disease development. LBW offspring from rats exposed to undernutrition during gestation (MUN) develops hypertension. In this rat model, we tested if slower postnatal growth improves early cardiometabolic alterations. MUN dams were fed ad libitum during gestation days 1–10, with 50% of the daily intake during days 11–21 and ad libitum during lactation. Control dams were always fed ad libitum. Pups were maintained with their own mother or cross-fostered. Body weight and length were recorded weekly, and breastmilk was obtained. At weaning, the heart was evaluated by echocardiography, and aorta structure and adipocytes in white perivascular fat were studied by confocal microscopy (size, % beige-adipocytes by Mitotracker staining). Breastmilk protein and fat content were not significantly different between groups. Compared to controls, MUN males significantly accelerated body weight gain during the exclusive lactation period (days 1–14) while females accelerated during the last week; length growth was slower in MUN rats from both sexes. By weaning, MUN males, but not females, showed reduced diastolic function and hypertrophy in the heart, aorta, and adipocytes; the percentage of beige-type adipocytes was smaller in MUN males and females. Fostering MUN offspring on control dams significantly reduced weight gain rate, cardiovascular, and fat hypertrophy, increasing beige-adipocyte proportion. Control offspring nursed by MUN mothers reduced body growth gain, without cardiovascular modifications. In conclusion, slower growth during lactation can rescue early cardiovascular alterations induced by fetal undernutrition. Exclusive lactation was a key period, despite no modifications in breastmilk macronutrients, suggesting the role of bioactive components. Our data support that lactation is a key period to counteract cardiometabolic disease programming in LBW and a potential intervention window for the mother.

Longitudinal associations of cumulative dyslipidaemia from mid-adolescence through young adulthood with arterial stiffness progression: the ALSPAC study

Abstract Background Arterial stiffness assessed with carotid-femoral pulse wave velocity (cfPWV) strongly predicts the risk of cardiovascular morbidity and mortality. Recent temporal causal evidence suggests that cfPWV progression may precede the development of cardiometabolic diseases in adolescence, young adults, and middle-aged adults. However, the longitudinal relationship between cfPWV progression and dyslipidaemia in the young population is unclear. Purpose To investigate the longitudinal associations of total cholesterol (TC), non–high-density lipoprotein cholesterol (non–HDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and low-density lipoprotein cholesterol (LDL-C) with cfPWV progression in adolescents. Methods We studied 1779 British 15-year-olds (50% females) followed up for 9 years. TC, triglyceride, and HDL-C were measured in line with standard protocols at ages 15, 17, and 24 years, respectively. LDL-C and non-HDL-C were estimated. Lipid phenotypes were categorized based on the 2011 National Heart, Lung, and Blood Institute classification into normal (reference), and elevated/dyslipidaemia. At age 17 and 24 years, cfPWV was computed from pressure waveforms obtained using the Vicorder device. We conducted linear mixed-effect model analyses and adjusted for sex, age, high sensitivity C-reactive protein, glucose, insulin, total fat mass, lean mass, heart rate, systolic blood pressure, diastolic blood pressure, sedentary time, light physical activity, moderate to vigorous physical activity, family history of cardiometabolic disease, socioeconomic status, pubertal attainment, and smoking status, in addition to lipid covariates such as HDL-C, LDL-C, or triglyceride depending on the predictor. However, TC and non-HDL-C analyses were not adjusted for lipids. Results Participants' mean (SD) age in years at different time points were 15.43 (0.29), 17.69 (0.31), and 24.53 (0.72). Persistently elevated/dyslipidaemia TC: effect estimate 0.006 m/s [95% CI −0.023 to 0.035; p=0.683], non–HDL-C: 0.004 m/s [−0.025 to 0.033; p=0.771], LDL-C: 0.017 m/s [−0.019 to 0.052; p=0.351], and Triglyceride: −0.009 m/s [−0.036 to 0.018; p=0.532] from 15 through 24 years were not cumulatively associated with the 7-year cfPWV progression. Persistent borderline-low/very-low HDL-C: 0.007 m/s [−0.017 to 0.031; p=0.556] was not associated with cfPWV progression. Conclusion These findings suggest that elevated lipids and dyslipidaemia from mid-adolescence through young adulthood were not associated with arterial stiffness progression, a marker of preclinical arteriosclerosis. Thus, lipid-lowering interventions targeted at preventing or reversing arterial stiffness progression in the young may be ineffective, particularly in a healthy young population. Funding Acknowledgement Type of funding sources: Private grant(s) and/or Sponsorship. Main funding source(s): Finnish Cultural Foundation

Association between Single Nucleotide Polymorphisms of SULT1A1, SULT1C4, ABCC2 and Phase II Flavanone Metabolites Excretion after Orange Juice Intake.

Citrus fruits and juices are a major source of dietary flavanones, and the regular consumption of these foods is inversely associated with the development of cardiometabolic diseases. However, the biological benefits depend on the bioavailability of these compounds, and previous studies have reported a large interindividual variability in the absorption and excretion of these compounds. Different factors, such as age, gender or genetic polymorphism of genes coding enzymes involved in the metabolism and transport of the flavanones, may explain this heterogeneity. This study aimed to assess the impact of single nucleotide polymorphism of sulfotransferases SULT1A1 and SULT1C4, and ABCC2 transporter genes on excretion of phase II flavanone metabolites in volunteers after 24 h of orange juice intake. Forty-six volunteers ingested a single dose of 500 mL of orange juice and 24-h urine was collected. The hesperetin and naringenin phase II metabolites were quantified in urine, and SNPs in SULT1A1, SULT1C4 and ABCC2 genes were genotyped. A significant (p < 0.05) relationship between the SNPs in these genes and the high excretion of phase II flavanone metabolites were observed. These results identified novel polymorphisms associated with higher absorption of flavanones, which may provide bases for future personalized nutritional guidelines for consuming flavanone-rich foods rich in these nutrients for better benefit from their health properties.

Inactivity and obesity: consequences for macrophage-mediated inflammation and the development of cardiometabolic disease.

Obesity and dyslipidaemia are strongly associated with the development of cardiometabolic diseases including CVD, stroke, type 2 diabetes, insulin resistance and non-alcoholic fatty liver disease. While these conditions are preventable, they are leading causes of mortality globally. There is now overwhelming clinical and experimental evidence that these conditions are driven by chronic systemic inflammation, with a growing body of data suggesting that this can be regulated by increasing levels of physical activity and reducing sedentary time. In this review we address the role of macrophage-mediated inflammation on the development of cardiometabolic diseases in individuals with overweight and obesity and how reducing sedentary behaviour and increasing physical activity appears to lessen these pro-inflammatory processes, reducing the risk of developing cardiometabolic diseases. While loss of subcutaneous and visceral fat mass is important for reducing chronic systemic inflammation, the mediating effects of increasing physical activity levels and lowering sedentary time on the development of inflamed adipose tissue also occur independently of changes in adiposity. The message that weight loss is not necessary for the benefits of physical activity in lowering chronic inflammation and improving health should encourage those for whom losing weight is difficult. Additionally, while the health benefits of meeting the recommended physical activity guidelines are clear, simply moving more appears to lower chronic systemic inflammation. Reducing sitting time and increasing light physical activity may therefore provide an alternative, more approachable manner for some with overweight and obesity to become more active, reduce chronic inflammation and improve cardiometabolic health.

THE ROLE OF CATESTATIN IN THE REGULATION OF METABOLIC DISORDERS. Review

Relevance. Cardiovascular diseases occupy leading positions in the structure of morbidity and mortality both in Ukraine and in other countries. Metabolic disorders are one of the leading risk factors for the development and progression of cardiovascular diseases. In accordance with the above-mentioned special attention should be paid to catestatin, which regulates carbohydrate and lipid metabolism, that determines its diagnostic potential in the management of diseases, which are accompanied by metabolic dysregulation.&#x0D; Objective: Determination of the diagnostic potential of catestatin in the management of diseases associated with metabolic disorders such as type 2 diabetes mellitus, obesity and metabolic syndrome, in accordance with its role in the regulation of metabolic homeostasis based on the analysis of data literature sources.&#x0D; Methods. Analysis of the research results by reviewing electronic scientometric databases PubMed and Google Scholar by keywords.&#x0D; Results. The influence of catestatin on the pathogenetic mechanisms of cardiometabolic diseases is analyzed. The general characteristic of catestatin and its physiological properties is given. The effect of catestatin on carbohydrate metabolism due to its insulin-like action is studied, which in combination with antioxidant, immunomodulatory and anti-inflammatory action of catestatin determines its role in the regulation of glucose metabolism. The property of catestatin to regulate cardiometabolic homeostasis by modulating the bioenergetic activity of the myocardium is noted. Mechanisms of regulation of fat metabolism by catestatin are established, in particular, realization of its lipolytic effect due to suppression of α2-adrenoreceptors and regulation of adrenergic and leptin signaling. Correlations between catestatin levels and lipid profile and anthropometric data are considered. Typical changes in catestatin levels at the development of cardiometabolic diseases are defined.&#x0D; Conclusions. Catestatin has metabolic effects, in particular, participates in the regulation of carbohydrate and lipid metabolism, which determines its prognostic role in the development and progression of cardiometabolic diseases.

Gut virome profiling identifies a widespread bacteriophage family associated with metabolic syndrome

There is significant interest in altering the course of cardiometabolic disease development via gut microbiomes. Nevertheless, the highly abundant phage members of the complex gut ecosystem -which impact gut bacteria- remain understudied. Here, we show gut virome changes associated with metabolic syndrome (MetS), a highly prevalent clinical condition preceding cardiometabolic disease, in 196 participants by combined sequencing of bulk whole genome and virus like particle communities. MetS gut viromes exhibit decreased richness and diversity. They are enriched in phages infecting Streptococcaceae and Bacteroidaceae and depleted in those infecting Bifidobacteriaceae. Differential abundance analysis identifies eighteen viral clusters (VCs) as significantly associated with either MetS or healthy viromes. Among these are a MetS-associated Roseburia VC that is related to healthy control-associated Faecalibacterium and Oscillibacter VCs. Further analysis of these VCs revealed the Candidatus Heliusviridae, a highly widespread gut phage lineage found in 90+% of participants. The identification of the temperate Ca. Heliusviridae provides a starting point to studies of phage effects on gut bacteria and the role that this plays in MetS.

Self-reported daytime napping, daytime sleepiness, and other sleep phenotypes in the development of cardiometabolic diseases: a Mendelian randomization study.

Sleep disorders are associated with an increased risk of cardiometabolic diseases in observational studies, but the causality remains unclear. In this study, we leveraged two-sample Mendelian randomization (MR) analyses to assess the causal associations of self-reported daytime napping, daytime sleepiness, and other sleep phenotypes with cardiometabolic diseases including ischaemic stroke (IS), coronary artery disease (CAD), heart failure (HF), and Type 2 diabetes mellitus (T2DM). We selected genetic variants as instrumental variables for self-reported daytime napping, daytime sleepiness, morning person, insomnia, short sleep duration, and long sleep duration from European-descent genome-wide association studies (GWASs). Summary statistics for cardiometabolic diseases originated from four different GWASs with a total of 2 500 086 participants. We used the inverse-variance weighted method to explore the role of self-reported sleep phenotypes on the aetiology of cardiometabolic diseases in the main analyses, followed by several sensitivity analyses for robustness validation. Genetically predicted self-reported daytime napping [T2DM: OR, 1.56 (95% confidence interval, 1.21-2.02)], insomnia [IS: OR, 1.07 (1.04-1.11)]; CAD: OR, 1.13 (1.08-1.17); HF: OR, 1.10 (1.07-1.14); T2DM: OR, 1.16 (1.11-1.22); and short sleep duration [CAD: OR, 1.37 (1.21-1.55)] were causally associated with an elevated risk of cardiometabolic diseases. Moreover, genetically determined self-reported daytime sleepiness [CAD: OR, 2.05 (1.18-3.57); HF: OR, 1.82 (1.15-2.87)] and morning person [HF: 1.06 OR, (1.01-1.11)] had potential detrimental effect on cardiometabolic risks. Self-reported daytime napping, insomnia, and short sleep duration had causal roles in the development of cardiometabolic diseases, while self-reported daytime sleepiness and morning person was the potential risk factor for cardiometabolic diseases.

Rheumatoid arthritis and the risk of major cardiometabolic diseases: a Mendelian randomization study

Objective Rheumatoid arthritis (RA) is suggested to be implicated in the development of cardiometabolic diseases. We conducted a Mendelian randomization (MR) study to assess potential causality for associations of RA with the risk of cardiometabolic diseases, including type 2 diabetes (T2D), coronary artery disease (CAD), and ischaemic stroke. Method Seventy independent single-nucleotide polymorphisms (SNPs) associated with RA were identified as instrumental variables from a genome-wide association study (GWAS) of 58 284 European subjects. Summary-level data for the associations of the 70 genetic variants with T2D, CAD, and ischaemic stroke were taken from three GWASs with a total of 1 529 131 participants. Inverse-variance weighted (IVW) MR was used in the main analyses. Results The main IVW MR analysis showed that genetically determined RA was associated with higher risks of T2D [odds ratio (OR): 1.04, 95% confidence interval (CI) 1.02–1.05; p < 0.001] and CAD (OR: 1.02, 95% CI 1.00–1.03; p = 0.012), but not ischaemic stroke (OR: 1.00, 95% CI 0.99–1.02; p = 0.961). Sensitivity analyses with multiple MR methods confirmed these associations. MR-Egger regression showed no evidence of pleiotropy in the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke. Leave-one-out sensitivity analysis showed that the association between genetically determined RA and the risk of T2D, CAD, and ischaemic stroke was not driven by any individual SNP. Conclusion Genetically determined RA was associated with increased risks of T2D and CAD, suggesting that RA plays a crucial role in the pathogenesis of T2D and CAD.

The Dose-Response Effects of Consuming High Fructose Corn Syrup-Sweetened Beverages on Hepatic Lipid Content and Insulin Sensitivity in Young Adults.

Increased hepatic lipid content and decreased insulin sensitivity have critical roles in the development of cardiometabolic diseases. Therefore, our objective was to investigate the dose-response effects of consuming high fructose corn syrup (HFCS)-sweetened beverages for two weeks on hepatic lipid content and insulin sensitivity in young (18–40 years) adults (BMI 18–35 kg/m2). In a parallel, double-blinded study, participants consumed three beverages/day providing 0% (aspartame: n = 23), 10% (n = 18), 17.5% (n = 16), or 25% (n = 28) daily energy requirements from HFCS. Magnetic resonance imaging for hepatic lipid content and oral glucose tolerance tests (OGTT) were conducted during 3.5-day inpatient visits at baseline and again at the end of a 15-day intervention. During the 12 intervening outpatient days participants consumed their usual diets with their assigned beverages. Significant linear dose-response effects were observed for increases of hepatic lipid content (p = 0.015) and glucose and insulin AUCs during OGTT (both p = 0.0004), and for decreases in the Matsuda (p = 0.0087) and Predicted M (p = 0.0027) indices of insulin sensitivity. These dose-response effects strengthen the mechanistic evidence implicating consumption of HFCS-sweetened beverages as a contributor to the metabolic dysregulation that increases risk for nonalcoholic fatty liver disease and type 2 diabetes.

Sex-Specific Associations Between Serum Phosphate Concentration and Cardiometabolic Disease: A Cohort Study on the Community-Based Older Chinese Population.

PurposeThis study aimed to investigate the association between sex-specific baseline serum phosphate and the incidence of new-onset cardiometabolic disease in a cohort of Shanghai-based older Chinese individuals.Patients and MethodsA community cohort of 5000 disease-free Chinese men and women was recruited in 2013 and followed until 2017 for the development of cardiometabolic disease. Participants underwent index and follow-up health screens at the Tongji Medical School affiliated Shanghai East Hospital, including blood biochemistry analysis, anthropometric measurements, interview on health-related behaviors, and clinical evaluation.ResultsHigher baseline serum phosphate (>1.25 mmol/L) was significantly associated with new-onset type-2 diabetes mellitus (HR 1.730, 95% CI 1.127–2.655) and metabolic syndrome (HR 0.640, 95% CI 1.085–2.155) in women. Baseline serum phosphate was associated with age, BMI, waist circumference, SBP, total calcium, bicarbonate, and total cholesterol in women. The estimated risk of developing diabetes mellitus in women with inorganic phosphate >1.25 mmol/L was 14.54%. Inorganic phosphate accounted for 9.2% of the variance explained in a total estimated 14.52% of variance attributed to BMI, total cholesterol, total calcium, waist circumference, and inorganic phosphate.ConclusionSerum phosphate concentration showed sex-specific associations with diabetes and metabolic syndrome. Higher inorganic phosphate was associated with increased risk of developing diabetes mellitus in women. These findings may be important in the assessment of individualized metabolic risk.