Metabolic Cardiovascular Disease Research Articles

Gut microflora and metabolic syndrome: new insight into the pathogenesis of hypertension

Emerging evidences indicate that a microbial imbalance (dysbiosis) is linked to several diseases including metabolic cardiovascular diseases. A fecal microbiota transplantation from hypertensive human donor to germ-free mice caused blood pressure elevation. In addition, there is a report demonstrating that angiotensin II-induced hypertension and vascular dysfunction were attenuated in germ-free mice, suggesting that gut microbiome may mediate development of hypertension. Although detailed mechanism by which the dysbiosis induces an increased blood pressure remains unknown, changes in microbiome may modify host immune systems and induce inflammatory dysfunction in cardiovascular system, resulting in dysregulation of blood pressure. Some cohort studies demonstrated an association between a higher abundance of Streptococcaceae spp. and blood pressure. One recent report demonstrated that an increasing number of gram-positive Streptococcus was found in the feces of adult spontaneously hypertensive rats with an increased intestinal permeability. We hypothesized that increased bacterial toxin levels derived from gut Streptococcus may be a factor inducing blood pressure dysregulation. In this review, we discuss the possible role of microbiome in cardiovascular disease, especially hypertension.

Burden of Chronic Conditions Among Persons with HIV/AIDS and Psychiatric Comorbidity.

Improved survivorship among persons living with HIV translates into a higher risk of medical comorbidities. We assessed the association between the intersection of physical (HIV) and mental health (psychiatric) conditions and intermediate outcomes. This was a cross-sectional study of the Medical Expenditure Panel Survey (MEPS)- Household Component between 1996 and 2016. We created four groups for persons aged ≥18: (1) HIV + psychiatric comorbidity, (2) HIV, (3) psychiatric comorbidity, and (4) no-HIV/no-psychiatric comorbidity. We compared the burden of medical comorbidities (metabolic disorders, cardiovascular disease, cancers, infectious diseases, pain, and substance use) among groups using chisquare tests. We used logistic regression to determine the association between group status and medical comorbidity. Of 218,133,630 (weighted) persons aged ≥18, 0.18% were HIV-positive. Forty-three percent of the HIV group and 19% of the no-HIV group had psychiatric comorbidities. Half of the HIV+ psychiatric disorder group had at least one medical comorbidity. Compared to the no- HIV/no-psychiatric comorbidity group, the HIV + psychiatric comorbidity group had the highest odds of medical comorbidity (OR= 3.69, 95% CI = 2.99, 4.52). Persons presenting with HIV + psychiatric comorbidity had higher odds of medical comorbidities of pain, cancer, cardiovascular disease, substance use, metabolic disorders and infectious diseases, beyond that experienced by persons with HIV infection or psychiatric disorders, independently. Future research will focus on the mediating effects of social determinants and biological factors on outcomes such as the quality of life, cost and mortality. This will facilitate a shift away from the single-disease framework and compress morbidity of the aging cohort of HIV-infected persons.

Sex Differences in Potentially Inappropriate Prescribing Among Older Adults With Multimorbidity

Sex differences in prescribing potentially inappropriate medications (PIMs) for various multimorbidity patterns are not well understood. This study sought to identify sex specific risk of PIMs in older adults with cardiovascular-metabolic patterns. Secondary analysis of the Health and Retirement Study interview data (2004-2014; n=6,341, ≥65 y/o) linked to Medicare claims data was conducted. Four multimorbidity patterns were identified based on the list of 20 chronic conditions and included: ‘cardiovascular-metabolic only’, ‘cardiovascular-metabolic plus other physical conditions’, ‘cardiovascular-metabolic plus mental conditions’, and ‘no cardiovascular-metabolic disease’ patterns. Presence of PIM prescribing was identified using the 2015 American Geriatrics Society Beers Criteria, limited to the list of medications to avoid in older adults. Chi-square tests and logistic regressions were used to identify sex differences in prescribing PIMs across multimorbidity patterns: (1) for PIMs overall and (2) for each PIM drug class. Results indicate that on average women were prescribed PIMs more often than men (39.4% and 32.8%, respectively). Women with cardiovascular-metabolic plus other physical patterns (Adj.OR=1.25, 95% CI: 1.07-1.45) and cardiovascular-metabolic plus mental patterns (Adj.OR=1.25, 95% CI: 1.06-1.48) had higher odds of PIM compared to men, however, there were no sex differences in PIM prescribing in the cardiovascular-metabolic only patterns (Adj.OR=1.13, 95% CI: 0.79-1.62). There was variation by sex across different PIM drug classes. Our study emphasizes the need to further reduce PIM prescribing among older adults, and identifies target populations for potential interventions to improve medication prescribing practices.

Comparison of Efficacy of the Pap and H & E in Identifying the Various Changes in Liver Samples of High Fat Diet Induced Rat - In vitro Study

Introduction: High fat induced (HFI) liver is associated with a high calorie intake and many other diet-induced complications, such as metabolic syndrome and cardiovascular disease. HFI is the most common chronic liver disease that develops due to high fat intake. A wide range of liver injuries is associated with HFI, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis and cirrhosis. The signs and symptoms of metabolic syndrome may be induced in rats by feeding them a diet rich in carbohydrates and fat. The aim of the study is Comparison of efficacy of the PAP (Papanicolaou) stain and H&E (Hematoxylin and eosin) stain in identifying the various changes in liver samples of high fat diet induced rat.
 Materials and Methods: Liver samples of Normal control group animal and High fat diet induced animal were sectioned, weighed fixed 10% neutral buffer formalin and mounted in DPX compound. Four micrometer sections were stained with hematoxylin-eosin and PAP stains for the histological examination of micro-vesicular and macro-vesicular steatosis in the liver tissue. The grading of steatosis was given from 0-3 based on the lipid accumulation (steatosis): grade 0 - absence; grade 1 - mild Steatosis (<30% hepatocyte); grade 2- moderate steatosis (30%-70% hepatocyte); grade3- severe steatosis (>70%hepatocytes). Efficacy of grade of PAP stain and H&E stain were accessed and statistically evaluated by considering seven parameters and overall staining characters where compared.
 Results: Our present study evaluated high fat induced hepatic steatosis of H&E and PAP stain and also evaluated efficacy of both the stain. In our study, Pie chart showing the percentage distribution of Number of micro-vesicles about 70% represents greater than 30, 10% represents 30-70, 20% represents less than 70 (Fig. 1). In our study 20% represents the greater than 30, 30% represents the 30-70, 50% represents Less than 70 (Fig. 2). 30% represents mild steatosis, 20% represents moderate steatosis, 50% represents Severe Steatosis (Fig. 3). 
 Conclusion: We demonstrated the comparative efficiency of the PAP and H&E high fat diet induced rat liver by in vivo and conclude that both H&E and PAP stain has equal efficacy and clarity in observing the various minute parameters.

Device-Based Sympathetic Nerve Regulation for Cardiovascular Diseases.

Sympathetic overactivation plays an important role in promoting a variety of pathophysiological processes in cardiovascular diseases (CVDs), including ventricular remodeling, vascular endothelial injury and atherosclerotic plaque progression. Device-based sympathetic nerve (SN) regulation offers a new therapeutic option for some CVDs. Renal denervation (RDN) is the most well-documented method of device-based SN regulation in clinical studies, and several large-scale randomized controlled trials have confirmed its value in patients with resistant hypertension, and some studies have also found RDN to be effective in the control of heart failure and arrhythmias. Pulmonary artery denervation (PADN) has been clinically shown to be effective in controlling pulmonary hypertension. Hepatic artery denervation (HADN) and splenic artery denervation (SADN) are relatively novel approaches that hold promise for a role in cardiovascular metabolic and inflammatory-immune related diseases, and their first-in-man studies are ongoing. In addition, baroreflex activation, spinal cord stimulation and other device-based therapies also show favorable outcomes. This review summarizes the pathophysiological rationale and the latest clinical evidence for device-based therapies for some CVDs.

Cardio-protective role of Humanin in myocardial ischemia-reperfusion

Mitochondria-derived peptides (MDPs) are bioactive peptides encoded by and secreted from the mitochondria. To date, a few MDPs including humanin, MOTS-c and SHLP1–6, and their diverse biological functions have been identified. The first and most studied MDP is humanin, a 24-amino-acid poly peptide. It was first identified in 2001 in the surviving neurons of patient with Alzheimer's disease, and since then has been well characterized for its neuro-protective effect through inhibition of apoptosis. Over the past two decades, humanin has been reported to play critical roles in aging as well as multiple diseases including metabolic disorders, cardiovascular diseases, and autoimmune disease. Humanin has been shown to modulate multiple biological processes including autophagy, ER stress, cellular metabolism, oxidative stress, and inflammation. A role for humanin has been shown in a wide range of cardiovascular diseases, such as coronary heart disease, atherosclerosis, and myocardial fibrosis. In this minireview, we will summarize the literature demonstrating a role for humanin in cardio-protection following myocardial ischemia-reperfusion induced injury and the potential mechanisms that mediate it.

Relationship Between Lipodystrophy, Body Composition, Metabolic Profile, and Serum Levels of Adipocytokines.

Background: Despite the benefits in improving the clinical state of people living with HIV/aids (PLWHA), some side effects associated with the use of antiretroviral therapy (ART) are reported. Redistribution of body fat has been associated with treatment and is characterized by morphological changes, also known as lipodystrophy. The complications of metabolic and morphological changes in these individuals seem to increase the risk of cardiovascular disease. Adipocytokines are proteins that have essential functions in biological processes, in which the levels of these proteins are related to the pathogenesis of metabolic syndrome (MS) and cardiovascular disease. Recent studies have shown that such levels are generally modified in PLWHA, regardless of whether the treatment is established or not. An application of methods for body fat estimation in patients with fat redistribution, as in the case of aids, especially those that quantify body fat by segments, appears to clarify these alterations and plays an important role in the development of multiprofessional treatment.Objectives: This investigation was carried out to compare and correlate body composition, biochemical metabolic parameters, and levels of adipocytokines and cytokines of PLWHA, with and without lipodystrophy, with individuals with negative HIV serology and stratified by sex.Material and Methods: This is a cross-sectional study in which body composition, metabolic and anthropometric changes, and levels of adipocytokines of 110 individuals were assessed. These individuals were paired in sex, age, and body mass index (BMI) and subdivided into three groups: PLWHA with and without a clinical diagnosis of lipodystrophy associated with HIV, and a group control.Results: Collinearity was identified both in the general sample and for genders of the waist-to-height ratio (WHtR) with all anthropometric parameters, except for muscle mass. The results show strong association between IFN-γ and TNF-α both in the general sample and for genders and moderate correlation between leptin and fasting glucose for women; worsening of the triglyceride profile in both women with lipodystrophy compared with the control group and men without lipodystrophy compared with the control group; higher serum TNF-α values among men without lipodystrophy compared to those with HIV-associated lipodystrophy (HALS).Conclusions: The results of this study underline that, considering the manifestations of the syndrome, these patients have a high-risk endocrine metabolic profile for cardiovascular events.

Population study of the gut microbiome: associations with diet, lifestyle, and cardiometabolic disease

BackgroundThe human gut harbors trillions of microbes that play dynamic roles in health. While the microbiome contributes to many cardiometabolic traits by modulating host inflammation and metabolism, there is an incomplete understanding regarding the extent that and mechanisms by which individual microbes impact risk and development of cardiovascular disease (CVD). The Framingham Heart Study (FHS) is a multi-generational observational study following participants over decades to identify risk factors for CVD by correlating genetic and phenotypic factors with clinical outcomes. As a large-scale population-based cohort with extensive clinical phenotyping, FHS provides a rich landscape to explore the relationships between the gut microbiome and cardiometabolic traits.MethodsWe performed 16S rRNA gene sequencing on stool from 1423 participants of the FHS Generation 3, OMNI2, and New Offspring Spouse cohorts. Data processing and taxonomic assignment were performed with the 16S bioBakery workflow using the UPARSE pipeline. We conducted statistical analyses to investigate trends in overall microbiome composition and diversity in relation to disease states and systematically examined taxonomic associations with a variety of clinical traits, disease phenotypes, clinical blood markers, and medications.ResultsWe demonstrate that overall microbial diversity decreases with increasing 10-year CVD risk and body mass index measures. We link lifestyle factors, especially diet and exercise, to microbial diversity. Our association analyses reveal both known and unreported microbial associations with CVD and diabetes, related prescription medications, as well as many anthropometric and blood test measurements. In particular, we observe a set of microbial species that demonstrate significant associations with CVD risk, metabolic syndrome, and type 2 diabetes as well as a number of shared associations between microbial species and cardiometabolic subphenotypes.ConclusionsThe identification of significant microbial taxa associated with prevalent CVD and diabetes, as well as risk for developing CVD, adds to increasing evidence that the microbiome may contribute to CVD pathogenesis. Our findings support new hypothesis generation around shared microbe-mediated mechanisms that influence metabolic syndrome, diabetes, and CVD risk. Further investigation of the gut microbiomes of CVD patients in a targeted manner may elucidate microbial mechanisms with diagnostic and therapeutic implications.

Exercise Training Intensity and the Fitness-Fatness Index in Adults with Metabolic Syndrome: A Randomized Trial

BackgroundCardiorespiratory fitness and fatness (notably central obesity) are mediating factors of the metabolic syndrome (MetS) and consequent cardiovascular disease (CVD)/mortality risk. The fitness-fatness index (FFI) combines these factors and has been reported to be a better indicator of CVD and all-cause mortality risk, beyond the capacity of either fitness or fatness alone.ObjectiveThis study sought to investigate the effects of different exercise intensities on FFI in adults with MetS.MethodsThis was a sub-study of the ‘Exercise in the prevention of Metabolic Syndrome’ (EX-MET) multicentre trial. Ninety-nine adults diagnosed with MetS according to the International Diabetes Federation criteria were randomized to one of the following 16-week exercise interventions: i) moderate-intensity continuous training (MICT) at 60–70% HRpeak for 30 min/session (n = 34, 150 min/week); ii) 4 × 4 min bouts of high-intensity interval training at 85–95% HRpeak, interspersed with 3-min active recovery at 50–70% HRpeak (n = 34, 38 min/session, 114 min/week); and iii) 1 × 4 min bout of HIIT at 85–95% HRpeak (n = 31, 17 min/session, 51 min/week). Cardiorespiratory fitness (peak oxygen uptake, V̇O2peak) was determined via indirect calorimetry during maximal exercise testing and fatness was the ratio of waist circumference-to-height (WtHR). FFI was calculated as V̇O2peak in metabolic equivalents (METs) divided by WtHR. A clinically meaningful response to the exercise intervention was taken as a 1 FFI unit increase.ResultsSeventy-seven participants completed pre and post testing to determine FFI. While there was no significant between group difference (p = 0.30), there was a small group x time interaction effect on FFI [F(2, 73) = 1.226; η2 = 0.01], with numerically greater improvements following HIIT (4HIIT, + 16%; 1HIIT, + 11%) relative to MICT (+ 7%). There was a greater proportion of participants who had a clinically meaningful change in FFI following high-volume HIIT (60%, 15/25) and low-volume HIIT (65%, 17/26) compared to MICT (38%, 10/26), but with no significant between-group difference (p = 0.12). A similar trend was found when a sub-analysis comparing the FFI between those with type 2 diabetes (MICT, 33%, 3/9; high-volume HIIT, 64%, 7/11; and low-volume HIIT, 58%, 7/12) and without type 2 diabetes (MICT, 41%, 7/17; high-volume HIIT, 57%, 8/14; low-volume HIIT, 71%, 10/14).ConclusionAlthough there were no statistically significant differences detected between groups, this study suggests that the response to changes in FFI in adults with MetS may be affected by exercise intensity, when numerical differences between exercise groups are considered. Further research is warranted.Trial registration number and date of registration: ClinicalTrials.gov NCT01676870; 31/08/2012.

Effect of two different fibre supplements on blood pressure, arterial stiffness and C-reactive protein in adults with overweight and obesity consumed over 12 months, in a randomised controlled trial

Adequate fibre consumption is associated with reduced risk of metabolic syndrome and cardiovascular disease. This study examined the effects of supplementation with PolyGlycopleX® (PGX®), a complex of 3 polysaccharides (fibre product), on blood pressure, arterial stiffness and C-reactive protein in overweight and obese participants. In this double-blind 12-month trial, participants were randomised into three groups: control (CTR; rice flour); PGX or a proprietary psyllium product (PSY). Participants added the 5 g supplements to their habitual diet and lifestyle, three times daily before meals. Between-groups analysis shows that systolic blood pressure was significantly lower in the PGX group at 3 months compared to CTR; stiffness index in the PGX group was significantly lower at 3 months compared to CTR. Within-group analysis shows systolic and diastolic blood pressure, as well as arterial stiffness, to be significantly lower in the PGX group at 3 months compared to baseline. While fibre supplementation may be an effective strategy to reduce chronic disease risk factors without the need for other dietary modifications, the present study suggests that more clinical trials with PGX are needed to clarify whether supplementing the with this product will reduce inflammation and improve vascular health in overweight and obese individuals. Trial registration: Australian New Zealand Clinical Trial Registry: ACTRN12611000415909. Registered 20 April 2011.

Mediterranean diet quality index is associated with better cardiorespiratory fitness and reduced systolic blood pressure in adults: A cross-sectional study.

Literature suggests higher cardiorespiratory fitness (CRF) is inversely related to chronic diseases such as metabolic syndrome and cardiovascular disease and hypertension. The aim of this study was to assess the association of Mediterranean dietary quality index (Med-DQI) with CRF and hypertension in a sample of Iranian adults. This was a cross-sectional study on 270 healthy men and women, aged 18-45 years. Dietary intake and physical activity level were assessed through a validated food frequency questionnaire (FFQ); and the International Physical Activity Questionnaires (IPAQ), respectively. Cardiorespiratory fitness was assessed by using a graded exercise treadmill test. The association between Med-DQI and CRF was investigated using multiple regression models. Participants in the top tertiles of Med-DQI, had higher VO2 max (mL/kg/min) (p=0.02) and lower SBP (p=0.01). When we controlled for age, sex, weight, smoking, physical activity and energy intake, the significant results were remained. Results of unadjusted linear regression shows that CRF was positively associated with cholesterol (p<0.001) and fish (p<0.001). Also, CRF was positively associated with vegetables and fruits (p<0.001) and olive oil (p=0.05). After adjustments for confounders, the significant associations of olive oil and cholesterol with CRF were disappeared while vegetables and fruits and total score of Med-DQI remained significant. There were no significant relations between saturated fatty acids meat, and cereals with Med-DQI. Our results demonstrated that Med-DQI was associated with better CRF in Iranian adults and SBP. Further studies with interventional approaches are needed to better clarify the causal inference of these associations.

The Effects of Bioavailability-Enhanced Curcuminoids on Serum Paraoxonase-1 Activity in Patients with Metabolic Syndrome

Introduction: Metabolic syndrome (MetS) is characterised by a clustering of metabolic cardiovascular disease (CVD) risk factors that include: central obesity, impaired glucose metabolism, dyslipidaemia (hypertriglyceridemia, increased low-density lipoprotein [LDL], decreased high-density lipoprotein [HDL]) and hypertension. Paraoxynase-1 (PON1) is a plasma HDL associated protein that inhibits the oxidation of other lipoproteins. There is some evidence of reduced enzyme activity in subjects with metabolic syndrome. Curcumin is a natural polyphenol, it has been reported that curcumin has beneficial effects on several metabolic syndrome associated parameters. The aim of this study was to evaluate the effect of phospholipid complex of curcumin as an antioxidant on the activity of this enzyme in subjects with metabolic syndrome.Materials and method: A double-blind randomised control study was undertaken in 80 patients with metabolic syndrome. Subjects in the intervention (n = 40) were given capsules of phospholipidated curcumin (1 g/day) for a period of 6 weeks. The control subjects (n = 40) received a placebo. Fasting blood samples of each person were obtained during the start and the end of the study. Paraoxonase activity was measured using a PON1 fluorescence Paraoxonase Assay Kit and Arylesterase activity was measured by photometeric method using a UV-Visible spectrophotometer.Results: Serum paraoxonase enzyme activity did not change significantly between the curcumin treated group and the control group before the intervention (0.54 ± 0.18 U/µl versus 0.49 ± 0.14 U/µl; P > 0.05), nor did serum arylesteras activity change significantly between two study groups (152.67 [46.60 to 916.05] U/µl versus 129.77 [55.34 to 344.78] U/µl; P > 0.05). In addition, there was no significant difference in changes at baseline and after the intervention in serum PON1 activity between the curcumin treated group and the control group (-0.03±0.19 U/µl versus -0.04±0.18 U/µl; P > 0.05), nor was there a significant change in arylesteras activity (-12.36 [-88.83 to 110.24] U/µl versus -4.58 [-61.06 to 47.07] U/µl; P > 0.05).Conclusion: Phospholipid fortified curcumin has no significant effect on serum PON1 activity.

Metabolic response against traffic congestion-induced stress

Background: Traffic congestion is a common problem in large cities, which can induce stress in participants in vehicles as well as pedestrians. In such conditions, several stress hormones, such as catecholamines and cortisol are secreted by the adrenal glands resulting in metabolic responses. Prolonged metabolic changes can lead to metabolic diseases, such as metabolic syndrome and cardiovascular disease. This study aimed to examine the metabolic responses induced by traffic congestion in young adults. Methods: We enrolled 71 undergraduate students aged 20-30 years from the Faculty of Medicine Universitas Islam Bandung, who regularly go to campus on foot, by public transportation, motorcycles, and cars. Medical history was screened by questionnaires before the testing day. Blood samples were drawn soon after participants arrived on campus. We used bioimpedance analysis to measure fasting blood glucose, lipid profiles, and nutrient body status. Results: Most participants rode motorcycles (46.48%), and the most common travel time was short (&lt;15 min, 54.9%.). Total cholesterol and low-density lipoprotein (LDL) levels were significantly lower in participants using vehicles - either private or public transportation - compared with pedestrians (p&lt;0.05 and p&lt;0.02, respectively). Participants with a short travel duration had significantly higher total cholesterol and LDL levels than those with longer ones (p&lt;0.02 and p&lt;0.05, respectively). Conclusions: Based on the above results, metabolic responses to traffic congestion such as changes to total cholesterol and LDL levels depended the type of transportation and travel duration.

Interplay between baroreflex sensitivity, obesity and related cardiometabolic risk factors (Review).

The baroreflex represents a rapid negative feedback system implicated in blood pressure regulation, which aims to prevent blood pressure variations by regulating peripheral vascular tone and cardiac output. The aim of the present review was to highlight the association between baroreflex sensitivity (BRS) and obesity, including factors associated with obesity, such as metabolic syndrome, hypertension, cardiovascular disease and diabetes. For the present review, a literature search was conducted using the PubMed database until August 21, 2021. The searched terms included ‘baroreflex’, and other terms such as ‘sensitivity’, ‘obesity’, ‘metabolic syndrome’, ‘hypertension’, ‘diabetes’, ‘gender’, ‘aging’, ‘children’, ‘adolescents’, ‘physical activity’, ‘bariatric surgery’, ‘autonomous nervous system’ and ‘cardiometabolic risk factors’. Obesity and its related metabolic disorders can influence baroreflex functionality and decrease BRS, mostly by potentiating sympathetic nervous system activity. Obesity induces inflammation, which can increase sympathetic system activity and lead to a higher incidence of cardiovascular events. Obesity also represents an important risk factor for hypertension through numerous mechanisms; in this setting, dysfunctional baroreceptors are not able to protect against constantly elevated blood pressure. Furthermore, diabetes mellitus and oxidative stress result in deterioration of BRS, whereas aging is also generally related to reduced cardiovagal BRS. Differences in BRS have also been observed between men and women, and overall cardiovagal BRS in healthy women is less intense compared with that in men. BRS appears lower in children with obesity compared with that in children of a healthy weight. Notably, physical exercise can increase BRS in both hypertensive and normotensive subjects, and BRS can also be significantly improved following bariatric surgery and weight loss. In conclusion, obesity and its related metabolic disorders may influence baroreflex functionality and decrease BRS, and baroreceptors cannot protect against the constantly elevated blood pressure in obesity. However, following bariatric surgery and weight loss, BRS can be significantly improved. The present review summarizes the role of obesity and related metabolic risk factors in BRS, providing details on possible mechanisms and shedding light on their interplay leading to autonomic neuropathy.

Relevance of mitochondrial dysfunction in heart disease associated with insulin resistance conditions.

Insulin resistance plays a key role in the development and progression of obesity, diabetes, and their complications. Moreover, insulin resistance is considered the principal link between metabolic diseases and cardiovascular diseases. Heart disease associated with insulin resistance is one of the most important consequences of both obesity and diabetes, and it is characterized by impaired cardiac energetics, diastolic dysfunction, and finally heart failure. Mitochondrion plays a key role in cell energy homeostasis and is the main source of reactive oxygen species. Obesity and diabetes are associated with alterations in mitochondrial function and dynamics. Mitochondrial dysfunction is characterized by changes in mitochondrial respiratory chain with reduced ATP production and elevated reactive oxygen species production. These mitochondrial alterations together with inflammation contribute to the development and progression of heart disease under insulin resistance conditions. Finally, numerous miRNAs participate in the regulation of energy substrate metabolism, reactive oxygen species production, and apoptotic pathways within the mitochondria. This notion supports the relevance of interactions between miRNAs and mitochondrial dysfunction in the pathophysiology of metabolic heart disease.

Abstract 14057: IL-19 Preserves the Metabolic Activity of Adipocytes in Obesity

Lack of compensatory vascularization causes hypoxia with adipose tissue dysfunction in obesity. Dysfunctional adipocytes instigate systemic low-grade inflammation which is associated with increased morbidity and mortality of metabolic disorders and related cardiovascular disease. A remaining challenge in the field is how to preserve adipocyte metabolic function by suppressing the negative aspect of inflammation, without blocking its angiogenic function. We investigated the role of IL-19, a uniquely immuno-modulatory, pro-angiogenic interleukin expressed also in adipose tissue. We hypothesize that IL-19 acts as a novel adipokine whose expression in expanding adipose depots is essential for maintaining glucose homeostasis. We report that IL-19 is expressed in adipose tissue at both the transcript and protein level and its expression is increased in inflamed visceral adipose tissue but not subcutaneous adipose tissue (p&lt;0.05). Utilizing Il19 -/- knockout mice, we found the loss of IL-19 leads to a metabolic phenotype characterized by reduced glucose and insulin tolerance, increased adipose tissue hypoxia and fibrosis, decreased adipose tissue vessel density and increased adipocyte hypertrophy both in response to standard chow diet and chronic high fat diet (p&lt;0.05). Acute treatment with IL-19 reduced glucose and insulin intolerance in obese wild-type mice (p&lt;0.05). In primary murine epididymal adipocytes the addition of IL-19 leads to increased glucose uptake (p&lt;0.05). These metabolic actions of IL-19 were linked to upregulation of the insulin type-2 receptor and subsequent increased expression/phosphorylation of the protein kinase B (Akt) in adipocytes. Overall, these data propose that IL-19 has novel therapeutic potential in that it can effectively allow adipose tissue expansion without concomitant inflammation and insulin insensitivity.

Postprandial Glycemic Dips Are Associated With Metabolic Disorders and CVD Risk in Euglycemic Individuals.

Metabolic disorders and cardiovascular disease (CVD) threaten human health. Many studies have assessed the phenomenon of metabolic disorders and CVD in patients with diabetes. However, in euglycemic individuals, the relationships between glucose regulation, metabolism, and CVD remain unclear. This work aimed to explore the associations between postprandial glucose dips, metabolic disorders, and CVD risk. We analyzed data from the Thyroid disorders, Iodine status and Diabetes Epidemiological survey (TIDE study), which included 38 878 euglycemic individuals from all 31 provinces of mainland China. The prevalence of metabolic disorders and their related components and CVD risk were calculated according to postprandial glucose dips. Logistic regression models of quartiles of postprandial glucose dips were used to further explore whether the prevalence of these disorders was associated with postprandial glucose dips. Odds ratios for the fourth vs the first quartile of glucose dips were 0.59 (95% CI, 0.55-0.63) (P < .001) for metabolic disorders, 0.48 (95% CI 0.44-0.53) (P < .001) for metabolic syndrome (MetS), and 0.54 (95% CI, 0.50-0.59) (P < .001) for hyperuricemia. The odds ratio of a 10-year CVD risk greater than 20% for the fourth vs the first glucose dip quartile was 0.67 (95% CI, 0.52-0.85) (P < .001). Models adjusted for body mass index yielded similar results. Postprandial glucose dips are associated with metabolic disorders, MetS and its related component diseases, and CVD risk. Glucose dips may be a marker of underlying metabolic abnormalities.

Sex Differences in Cardiovascular Impact of Early Metabolic Impairment: Interplay between Dysbiosis and Adipose Inflammation.

The evolving view of gut microbiota has shifted toward describing the colonic flora as a dynamic organ in continuous interaction with systemic physiologic processes. Alterations of the normal gut bacterial profile, known as dysbiosis, has been linked to a wide array of pathologies. Of particular interest is the cardiovascular-metabolic disease continuum originating from positive energy intake and high-fat diets. Accumulating evidence suggests a role for sex hormones in modulating the gut microbiome community. Such a role provides an additional layer of modulation of the early inflammatory changes culminating in negative metabolic and cardiovascular outcomes. In this review, we will shed the light on the role of sex hormones in cardiovascular dysfunction mediated by high-fat diet-induced dysbiosis, together with the possible involvement of insulin resistance and adipose tissue inflammation. Insights into novel therapeutic interventions will be discussed as well. SIGNIFICANCE STATEMENT: Increasing evidence implicates a role for dysbiosis in the cardiovascular complications of metabolic dysfunction. This minireview summarizes the available data on the sex-based differences in gut microbiota alterations associated with dietary patterns leading to metabolic impairment. A role for a differential impact of adipose tissue inflammation across sexes in mediating the cardiovascular detrimental phenotype following diet-induced dysbiosis is proposed. Better understanding of this pathway will help introduce early approaches to mitigate cardiovascular deterioration in metabolic disease.

Older Adults and Serious Mental Illness: What We Know and What We Imagine

Older Adults and Serious Mental Illness: What We Know and What We Imagine

Highly Active Antiretroviral Therapy in Adult HIV-Infected Patients with Diabetes Mellitus: A 5-year Prospective Cohort Study

Adverse effects following long-term use of highly active antiretroviral therapy (HAART), such as metabolic syndromes (MetS) and cardiovascular diseases (CVDs), have been reported. We determined whether patients with controlled pre-existing diabetes mellitus (DM) undergoing HAART are at high risk of long-term adverse effects, compared with HIV-infected patients without DM. In this prospective cohort study that recruited 172 HIV-infected patients, patients were followed up every six months for five years. Data Collection on Adverse Effects of Anti-HIV Drugs (D:A:D), a CVD risk score for HAART, and lab data, were compared between patients with controlled DM and non-DM patients matched on age and gender. HAART was less effective for HIV-infected patients with DM, with a higher plasma HIV RNA load in plasma viral load (PVL) testing (r=0.4868, P=0.0216) since the third year of follow-up. HAART increased the risk of CVDs for DM patients, with higher D:A:D (R) (r=0.1636, P=0.0336) and D:A:D (F) (r=0.1883, P=0.0142) scores at fifth year. DM patients presented with higher risk of advanced stages CKD (GFR<30 mL/min) (r=0.3226, P< 0.0001), with increased creatinine (r=0.5669, P<0.0001) and BUN (r=0.2832, P=0.0009). As of MetS, DM patients had increased waist circumference (r=0.2601, P=0.0006), total cholesterol (CHO) (r=0.2745, P=0.0309), LDL (r=0.1925, P=0.0402), compared to baseline. Even though under controlled status at baseline, DM patients still had higher fasting blood sugar since the third year (r=0.3129, P=0.0002). In conclusion, HAART was less effective in DM patients, and resulted in more subsequent CVDs and renal toxicities; other signs of metabolic syndromes were as well observed.