Cardiometabolic Changes Research Articles

Does Switching Antipsychotics Ameliorate Weight Gain in Patients With Severe Mental Illness? A Systematic Review and Meta-analysis.

Obesity and adverse metabolic outcomes in patients with severe mental illness are clinically significant but potentially preventable. Importantly, the evidence for switching to antipsychotics to reduce cardiometabolic burden is unclear. PubMED, Embase, PsycINFO, and Cochrane were searched from inception to March 8, 2020. Articles reporting weight and metabolic changes after antipsychotic switching vs staying on the previous antipsychotic were meta-analyzed both across and within group. Of 61 identified studies, 59 were meta-analyzed (40% rated high quality). In the switch-vs-stay pairwise meta-analyses, only aripiprazole significantly reduced weight (-5.52 kg, 95% CI -10.63, -0.42, P = .03), while olanzapine significantly increased weight (2.46 kg, 95% CI 0.34, 4.57, P = .02). Switching to aripiprazole also significantly improved fasting glucose (-3.99 mg/dl, 95% CI -7.34, -0.64, P = .02) and triglycerides (-31.03 mg/dl, 95% CI -48.73, -13.34, P = .0001). Dropout and psychosis ratings did not differ between switch and stay groups for aripiprazole and olanzapine. In before-to-after switch meta-analyses, aripiprazole (-1.96 kg, 95% CI -3.07, -0.85, P < .001) and ziprasidone (-2.22 kg, 95% CI -3.84, -0.60, P = .007) were associated with weight loss, whereas olanzapine (2.71 kg, 95% CI 1.87, 3.55, P < .001), and clozapine (2.80 kg, 95% CI 0.26, 5.34, P = .03) were associated with weight gain. No significant weight or other cardiometabolic changes were observed when switching to amisulpride, paliperidone/risperidone, quetiapine, or lurasidone. Switching antipsychotics to agents with lower weight gain potential, notably to aripiprazole and ziprasidone, can improve weight profile and other cardiometabolic outcomes. When choosing switch agents, both the weight gain potential of the pre- and post-switch antipsychotic must be considered. Antipsychotic switching in psychiatrically stable patients must be weighed against the risk of psychiatric worsening.

EVALUATION OF HORMONAL AND METABOLIC PARAMETERS, ALONG WITH CARDIOVASCULAR RISK FACTORS IN WOMEN WITH NON-ALCOHOLIC FATTY LIVER DISEASE COMBINED WITH SUBCLINICAL HYPOTHYROIDISM DEPENDING ON AGE

Patients with NAFLD (non-alcoholic fatty liver disease) and subclinical hypothyroidism are at risk of cardiovascular complications that cause cardiometabolic changes, thus enabling to broaden our understanding of the cardiovascular events risk in a comorbid patient.&#x0D; The aim: The study of hormonal and metabolic indicators and cardiovascular risk factors in women from NAFLD combined with SH (subclinical hypothyroidism) depending on the age.&#x0D; Materials and methods: 128 patients with NAFLD were studied, which were divided into 2 groups: І group – patients with NAFLD and level of thyroid-stimulating hormone (TSH) – 4 to 10 mIU/mL (n=45), ІІ group - patients with NAFLD and level of TSH &gt;10 mIU/mL (n=49). The control group consisted of 34 NAFLD patients without SH. Depending on the level of TSH and age, degree of cardiovascular risk, indicators of carbohydrate and lipid metabolism, as well as the indicators that reflect ED were evaluated.&#x0D; Results: Comparison of metabolic parameters in two groups showed a significant difference (p&lt;0.01 between indicators depending on the TSH level, where patients were below 50 years of age: HbA1c, LDL cholesterol, HDL cholesterol, gamma-glutamyltranspeptidase (GGTP). The levels of CDEC (circulating desquamated endothelial cells), VEGF (vascular endothelial growth factor), CRP (C-reactive protein) and TNF-α (tumor necrosis factor-α) were dependent not only on TSH, but also on age. Significant differences (p=0.001) were obtained in patients aged ≤ 50 years: CDEC; VEGF, CRP; TNF-α.&#x0D; Conclusions: Patients from NAFLD combined with SH have hormonal-metabolic disorders, and their degree depends on the TSH level. Early cardiometabolic changes in women are formed already at the age under 50 years, which indicates the formation of early atherosclerotic vascular changes

Increase in arterial stiffness measures after bariatric surgery

Background and aimsThe relationship between obesity and arterial stiffness is complex, with a potential interaction by age (inverse association at younger age and positive at older age) and conflicting reports on the effect of lifestyle-based weight loss on arterial stiffness. Little is understood about post-bariatric surgery changes in arterial stiffness. This study aimed to examine post-bariatric surgery changes in arterial stiffness and identify factors associated with greater changes in arterial stiffness. MethodsIn 72 patients (mean age 44.5 years, 72.2% female), we evaluated two arterial stiffness measures, cardio-ankle vascular index (CAVI) and heart-ankle pulse wave velocity (haPWV), one month prior to and 6 months after bariatric surgery. Another follow-up visit was conducted 12 months after bariatric surgery in a subset of 58 participants. ResultsSix months after bariatric surgery, an evident decrease was seen in body mass index, heart rate, and systolic blood pressure. In contrast, both CAVI and haPWV significantly increased at 6 months (+0.64 [0.42, 0.87] and +0.24 [0.04, 0.44] m/s, respectively). Among 58 patients with relevant data, CAVI and haPWV remained elevated 12 months after bariatric surgery (+0.80 [0.53, 1.07] and +0.40 [0.17, 0.62] m/s, respectively). Being non-diabetic and having larger decreases in post-surgery heart rate were independently associated with greater increases in post-surgical CAVI. ConclusionsArterial stiffness measures, CAVI and haPWV, were elevated after bariatric surgery despite other favorable cardiometabolic changes. Further studies are necessary to elucidate the underlying mechanism and prognostic implications of this elevation in arterial stiffness measures after bariatric surgery.

Metabolic syndrome during gestation and lactation: An important renal problem in dams. selenium renal clearance

BackgroundMetabolic syndrome (MS) in lactating dams leads to several cardiometabolic changes related to selenium (Se) status and selenoproteins expression which produce hypertension. However, little is known about the state of these dams’ kidney functions and their Se deposits. MethodsTwo experimental groups of dam rats were used: control (Se: 0.1 ppm) and MS (Fructose 65 % and Se: 0.1 ppm). At the end of lactation (21d postpartum) kidney weight and protein content, Se deposits, and the activity of the antioxidant selenoprotein glutathione peroxidase (GPx) were measured in dams. Kidney functional parameters: albuminuria, creatinine clearance, serum aldosterone and uric acid levels and water and electrolyte (Na+ and K+) balance were also evaluated. Systolic blood pressure (SBP) was measured. ResultsIn MS dams at the end of lactation Se deposits and GPx activity are higher in the kidney; however, lipid renal peroxidation appears, relative Se clearance increases, and the dams have lost Se by urine. MS dams have polyuria and polydipsia, high uric acid serum levels, albuminuria and high creatinine clearance, implying glomerular renal malfunction with protein loss. They also present hypernatremia, hypokalemia and hyperaldosteronemia, leading to high SBP; however, a natriuretic process is taking place. ConclusionSince these alterations appear, at least in part, to be related to oxidative stress in renal cells, Se supplementation could be beneficial to avoiding greater lipid renal oxidation during lactation.

Cardiometabolic risk and health behaviours in adolescents with normal-weight obesity: a systematic review.

To analyse the presence of cardiometabolic risk factors in adolescents with normal-weight obesity (NWO), as well as to investigate health behaviours related to the phenotype. The study was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines and the bibliographic search was carried out in the PubMed, Scielo and ScienceDirect databases. School, university and population. Adolescents between 10 and 19 years old. A total of eight papers were included. Most studies have found a relationship between NWO and the presence of cardiometabolic risk factors, such as high waist circumference, unfavourable lipid and glycid profile. As for health behaviours, three of the eight studies included evaluated eating habits; however, the results were not conclusive. In addition, four studies analysed the practice of physical activity or physical fitness, which was lower in NWO. The available evidence indicates that NWO is related to the early development of cardiometabolic changes, physical inactivity and less physical fitness in adolescents. The results also reveal the importance of early detection of the phenotype, as well as the need for further research on the associated factors to prevent future diseases. Registration (PROSPERO: CRD42020161204).

Plasma lipidome abnormalities in people with HIV initiating antiretroviral therapy

BackgroundDyslipidemia often accompanies human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART). Lipid abnormalities likely contribute to increased cardiometabolic disease among people with HIV (PWH). Here, we expand our previous findings on changes in the lipidome following ART initiation, and associations among lipid species, including ceramides (CER), diacylglycerols (DAG), and triacylglycerols (TAG), with immune activation.MethodsConcentrations and fatty acid composition of plasma lipids (~ 1300 species) were measured by differential mobility spectroscopy in samples from 35 treatment-naïve PWH pre- and post-initiation of ART (raltegravir (RAL)/tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC)); lipidomes were compared to those found in demographically similar HIV-uninfected individuals (n = 13).ResultsCompared to people without HIV, 37.1% of all lipid species measured were altered in PWH at baseline, and 31.8% of lipid species were altered following 48 weeks of ART. Concentrations of lipid classes were also altered in PWH; diacylglycerols (DAGs) and triacylglycerols (TAGs) were increased at baseline, and DAGs remained increased after 48 weeks of ART. Lipids previously linked to cardiovascular disease (CVD) and diabetes were enriched in PWH pre- and post ART, and were related to immune activation and insulin resistance scores. Polyunsaturated fatty acid (PUFA)-containing lipids were lower in PWH compared to levels in controls, and were inversely related to levels of inflammatory biomarkers.ConclusionsHIV infection and ART initiation both induce cardiometabolic changes to the composition of the plasma lipidome. These alterations are associated with inflammatory biomarkers, and may directly contribute to elevated CVD risk and diabetes.Trial registrationThis study is registered with Clinicaltrials.gov (NCT00660972). Registered April 16, 2008.

Abstract 15634: High-fat Diet Consumption Accelerates Cardiometabolic Impairment via Deteriorating Mitochondrial Function in Non-obese Spontaneously Type 2 Diabetic Rats

Introduction: Type 2 Diabetes Mellitus (T2DM) is a complex disease which is related to genetic, environmental, and lifestyle factors. In genetically-induced T2DM rats, normal diet could induce spontaneous diabetes, and induce left ventricular (LV) dysfunction over time. However, the effect of high-fat diet (HFD) in these genetically-induced T2DM rats on the cardiometabolic changes, including LV function and cardiac mitochondrial function has rarely been investigated. Hypothesis: High-fat diet (HFD) consumption accelerates the development of T2DM and LV dysfunction by inducing mitochondrial dysfunction in genetically-induced non-obese T2DM-Spontaneously Diabetic Torii (SDT) rats. Methods: Male SDT rats (n=18/group) were divided into 2 groups to receive either normal diet (ND, 19.77% fat) or HFD (57.60% fat) for 4, 8 or 12 weeks. At each time course, cardiac function determined by echocardiography and the pressure-volume loop determined by invasive intracardiac catheterization were assessed. The heart was removed to study cardiac mitochondrial function at each time-course. Results: The body weight, food intake, and visceral fat were not different between ND and HFD rats at any times. Increased blood glucose was seen earlier at week 4 in HFD rats, but later at week 12 in ND rats. The development of LV contractile dysfunction and decreased stroke volume was observed earlier at week 8 in HFD rats, compared to ND rats and HFD rats at the baseline. Increased cardiac mitochondrial ROS production and decreased mitochondrial membrane potential (i.e. mitochondrial depolarization) was observed earlier at week 8 in HFD rats, compared to ND rats (Fig). Conclusions: High-fat diet accelerates cardiometabolic impairments via impaired cardiac mitochondrial function in genetically-induced non-obese T2DM rats.

Abstract 14055: Impact of a Boxed Meal Facilitated Plant-based Diet on Cardiometabolic Endpoints: A Clinical Trial

Background: Plant-based diets (PBD) are increasingly recommended to reduce the risk of cardiovascular disease. Boxed meal-delivery services are a growing market facilitating consumer convenience; however, their effects on health require further study. We compared cardiometabolic changes between a boxed meal facilitated PBD (f-PBD) and Standard Omnivorous Diet (f-SOD). Methods: A prospective, controlled, parallel-designed trial assessing the impact of a f-PBD (n=16) to a f-SOD (n=16) on cardiometabolic endpoints was conducted in military beneficiaries. Participants with a BMI &gt;25 kg/m 2 consuming a standard omnivorous diet volunteered to adopt a f-PBD or f-SOD for a 4-week period. Participants had the option to consume breakfast and lunch according to their adopted diet at the military dining facility. Dinner was facilitated by shipping a commercially available plant-based or standard omnivorous boxed meal kit to participants as appropriate. Lipid parameters were monitored at baseline and at 4 weeks. Weight, blood pressure (BP) and other clinical endpoints were assessed weekly. The primary endpoints were change from baseline at 4 weeks in calculated low-density lipoproteins (LDL-c) and weight. A student’s t-test was performed to assess differences between groups using the intention-to-treat methodology. Results: A total of 32 participants were enrolled in the f-PBD and f-SOD groups. Average age of participants was 33.3±7.8 years, BMI was 29.6±3.5 kg/m 2 and 50% were male. Change in LDL-c from baseline in the f-PBD and f-SOD groups were -9.41±21.7 mg/dl and +5.63±15.9 mg/dl, respectively (p=0.033). The change in weight from baseline in the f-PBD and f-SOD groups were -3.82±4.4 pounds and +0.87±2.7 pounds, respectively (p=0.001). Systolic BP decreased non-significantly in the f-PBD group (-4.88±5.4 mmHg vs -0.38±9.2 mmHg for f-PBD and f-SOD, respectively, p=0.103). Conclusion: Incorporating a meal-delivery f-PBD significantly reduced LDL-c and weight over a 4-week period. Plant-based meal kits could serve as a novel dietary intervention in the optimization of cardiovascular disease burden.

Abstract 16839: Maternal Placental Vascular Malperfusion Lesions Associated With Increased Cardiometabolic Risk and Reduced Microvascular Density in Women a Decade After Delivery: Which Placental Features Matter?

Introduction: Maternal vascular malperfusion (MVM) lesions in the placenta are commonly found in women with adverse pregnancy outcomes associated with increased CVD in later life. Minimal criteria for MVM include vasculopathy, accelerated villous maturation and increased syncytial knots, and villous infarction upon pathologic examination; expanded definitions have included presence of fibrin deposition (intervillous or perivillous) or low placental weight (&lt;10 th %). Hypothesis: Women with a history of MVM lesions would have evidence of cardiometabolic risk factors and peripheral microvascular changes a decade after delivery independent of pregnancy outcome. Methods: A total of 469 women with placental pathology data available were evaluated at 8-10 years postpartum. Placental specimens were reviewed by a perinatal pathologist. Cardiometabolic variables were measured at the time of the study visit. Sidestream dark field imaging was used to assess the sublingual microcirculation. We compared the median size (diameter) of microvessels, density (total length of perfused microvessels/mm 2 ) and penetration of red cells into the glycocalyx of vessels 5-25μm diameter (perfused boundary region, PBR) in women 8-10 years after pregnancy, using the minimal MVM criteria (compared to none). Expanded criteria were examined alone. Significance =*p&lt;0.05 vs no MVM lesions. Results: Women with minimally defined MVM lesions in their placentas had higher diastolic blood pressure (79mmHg MVM vs. 75 mmHg No MVM*), LDL (111mg/dL MVM vs. 101 mg/dL No MVM*), Cholesterol (185 mg/dL MVM vs. 175mg/dL No MVM*) and insulin (14mg/dL MVM vs. 12mg/dL No MVM*), along with smaller-sized microvessels (median 8.75±1.1 μM vs. 9.06±0.7 μM*), and a lower density of perfused microvessels compared to women without MVM lesions (3590±1260mm/mm 2 MVM vs. 3970±820 mm/mm 2 No MVM*) a decade after delivery. Glycocalyx PBR was smaller in women with prior MVM vs. women without lesions (2.01±0.23μm vs. 2.09±0.15μm, P=0.02). Similar results were not seen in subjects with either presence of fibrin or small placenta in the absence of other MVM criteria. Discussion: Using minimal criteria MVM was associated most strongly with maternal cardiometabolic and microvascular differences a decade later.

Gestational diabetes status and dietary intake modify maternal and cord blood allostatic load markers

IntroductionAllostatic load (AL) defines cardiometabolic, inflammatory, and neuroendocrine changes in the body in response to internal and external stressors. It is largely unknown whether gestational diabetes mellitus (GDM) alters maternal...

Microbiome Understanding in Maternity Study (MUMS), an Australian prospective longitudinal cohort study of maternal and infant microbiota: study protocol.

IntroductionPregnancy induces significant physiological and cardiometabolic changes, and is associated with alterations in the maternal microbiota. Increasing rates of prepregnancy obesity, metabolic abnormalities and reduced physical activity, all impact negatively on the microbiota causing an imbalance between the commensal microorganisms (termed dysbiosis), which may drive complications, such as gestational diabetes or hypertensive disorders. Considerable work is needed to define the inter-relationships between the microbiome, nutrition, physical activity and pregnancy outcomes. The role of the microbiota during pregnancy remains unclear. The aim of the study is to define microbiota signatures longitudinally throughout pregnancy and the first year post birth, and to identify key clinical and environmental variables that shape the female microbiota profile during and following pregnancy.Methods and analysisThe Microbiome Understanding in Maternity Study (MUMS) is an Australian prospective longitudinal cohort study involving 100 mother–infant pairs. Women are enrolled in their first trimester and followed longitudinally. Assessment occurs at <13+0, 20+0–24+6 and 32+0–36+6 weeks gestation, birth and 6 weeks, 6 months and 12 months postpartum. At each assessment, self-collected oral, vaginal and faecal samples are collected with an additional postpartum skin swab and breastmilk sample. Each infant will have oral, faecal and skin swab samples collected. Measurements include anthropometrics, body composition, blood pressure, serum hormonal and metabolic parameters and vaginal pH. Dietary intake, physical activity and psychological state will be assessed using validated self-report questionnaires, and pregnancy and infant outcomes recorded. Parametric and non-parametric hypothesis tests will be used to test the association between high-risk and low-risk pregnancies and their outcomes.Ethics and disseminationThe study received the following approval: South Eastern Sydney Local Health District Research Ethics Committee (17/293 (HREC/17/POWH/605). Results will be made available to the participants of MUMS, their families and the funding bodies; in the form of a summary document. Results for the greater maternity care community and other researchers will be disseminated through conferences, local, national and international presentations and peer-reviewed publications.Trial registration numberACTRN12618000471280 (prospectively registered).

Antioxidants and Oxidative Stress in Children: Influence of Puberty and Metabolically Unhealthy Status.

Oxidative stress could help explain the relationship between childhood obesity and a metabolically unhealthy (MU) status. Moreover, puberty could also influence this relationship, since it entails physiological cardiometabolic changes. We aimed to evaluate plasma antioxidants and oxidative stress biomarkers in MU and metabolically healthy (MH) prepubertal and pubertal children and their associations with pro-inflammatory and endothelial damage biomarkers, taking puberty into account. A total of 1444 Spanish children aged 3–17 years (48.9% males, 66% prepubertal, 47.1% with obesity) were recruited. Blood pressure, anthropometric and biochemical parameters were measured, and children were categorized as having a MU or MH status according to risk factors. Retinol, carotenes, tocopherols, total antioxidant capacity (TAC), oxidized low-density lipoprotein and selected pro-inflammatory and endothelial damage biomarkers were analyzed. General linear models adjusted for age, sex, recruitment center and body mass index, partial correlations and stepwise linear regressions were performed. Lower carotenes and tocopherols levels were found in MU than in MH children. Plasma TAC was lower in prepubertal and higher in pubertal children with obesity compared to normal-weight children. Antioxidants and oxidative stress biomarkers showed novel associations with several pro-inflammatory and endothelial damage biomarkers, with pubertal differences, supporting the importance of considering both the antioxidant and oxidative stress status and puberty in the prevention of metabolic diseases in childhood.

Aerobic training prevents cardiometabolic changes triggered by myocardial infarction in ovariectomized rats.

This study aimed to evaluate the impact of aerobic training (AT) on autonomic, cardiometabolic, ubiquitin-proteasome activity, and inflammatory changes evoked by myocardial infarction (MI) in ovariectomized rats. Female Wistar rats were ovariectomized and divided into four groups: sedentary + sham (SS), sedentary + MI (SI), AT + sham surgery (TS), AT + MI (TI). AT was performed on a treadmill for 8 weeks before MI. Infarcted rats previously subjected to AT presented improved physical capacity, increased interleukin-10, and decreased pro-inflammatory cytokines. Metabolomic analysis identified and quantified 62 metabolites, 9 were considered significant by the Vip Score. SS, SI, and TS groups presented distinct metabolic profiles; however, TI could not be distinguished from the SS group. MI dramatically increased levels of dimethylamine, and AT prevented this response. Our findings suggest that AT may be useful in preventing the negative changes in functional, inflammatory, and metabolic parameters related to MI in ovariectomized rats.

Consuming an Energy-Restricted US Healthy-Style Eating Pattern Moderate or High in Protein Confers Comparable Changes in Body Composition and Cardiometabolic Health

Abstract Objectives Several systematic reviews and meta-analyses demonstrate consuming higher versus lower protein diets attenuates lean mass loss during energy restriction. No study to date has tested this phenomenon when consuming more dietary protein than prescribed as part of a US Healthy-Style Eating Pattern (USHEP). We sought to assess the effects of consuming a USHEP with either the recommended or a higher amount of protein during energy-restriction on body composition and fasting cardiometabolic disease risk factor changes. Methods Using a randomized, parallel-design, 51 men and women (mean ± SEM; age: 47 ± 1 y; BMI: 32.6 ± 0.5 kg/m2) consumed a controlled USHEP containing 750 kcal/d less than their estimated energy requirement for 12 wk. Participants were randomized to consume either 5 oz-eq/d or 12.5 oz-eq/d of protein foods. The additional dietary protein (7.5 oz-eq/d) from animal-based protein sources displaced predominantly whole and refined grains. Body composition (air displacement plethysmography) and fasting cardiometabolic health risk factors were measured at pre-, mid- (week 6), and post-intervention (week 12). Results Dietary protein intake did not affect any of the body composition or fasting cardiometabolic disease risk factors measured. Among all participants, over time, body mass (−6.2 ± 0.4 kg), fat mass (−6.9 ± 0.6 kg), and fat mass % body mass (−5.3 ± 0.6%) decreased (all P &amp;lt; 0.001). Lean mass (0.7 ± 0.5 kg) did not change and lean mass % body mass (5.3 ± 0.6%) increased (P &amp;lt; 0.001). Fasting serum insulin (−4.2 ± 0.9 μU/mL), total cholesterol (−17 ± 3 mg/dL), high-density lipoprotein cholesterol (−5 ± 1 mg/dL), low-density lipoprotein cholesterol (−7 ± 3 mg/dL), and triglyceride (−24 ± 6 mg/dL) concentrations, and seated systolic (-5 ± 1 mm Hg) and diastolic (−5 ± 1 mm Hg) blood pressures, each decreased over time (all P &amp;lt; 0.001). Conclusions Improvements in body composition and cardiometabolic health in overweight adults can be achieved by consuming a US Healthy-Style Eating Pattern with either the recommended amount of protein or higher protein from animal-based sources during weight loss. Funding Sources The Beef Checkoff and American Egg Board-Egg Nutrition Center.

Prematurity With Extrauterine Growth Restriction Increases the Risk of Higher Levels of Glucose, Low-Grade of Inflammation and Hypertension in Prepubertal Children

Introduction: An adipose tissue programming mechanism could be implicated in the extrauterine growth restriction (EUGR) of very preterm infants with morbidity in the cardiometabolic status later in life, as has been reported in intrauterine growth restriction. The aim of this study was to assess whether children with a history of prematurity and EUGR, but also with an adequate growth, showed alterations in the metabolic and inflammatory status.Methods: This was a case–control study. A total of 88 prepubertal children with prematurity antecedents were selected: 38 with EUGR and 50 with an adequate growth pattern (PREM group). They were compared with 123 healthy children born at term. Anthropometry, metabolic parameters, blood pressure (BP), C-reactive protein, hepatocyte growth factor (HGF), interleukin-6 (IL-6), IL-8, monocyte chemotactic protein type 1 (MCP-1), neural growth factor, tumour necrosis factor-alpha (TNF-α) and plasminogen activator inhibitor type-1 were analysed at the prepubertal age.Results: EUGR children exhibited higher BP levels and a higher prevalence of hypertension (46%) compared with both PREM (10%) and control (2.5%) groups. Moreover, there was a positive relationship between BP levels and values for glucose, insulin and HOMA-IR only in children with a EUGR history. The EUGR group showed higher concentrations of most of the cytokines analysed, markedly higher TNF-α, HGF and MCP-1 levels compared with the other two groups.Conclusion: EUGR status leads to cardiometabolic changes and a low-grade inflammatory status in children with a history of prematurity, and that could be related with cardiovascular risk later in life.

EFFECT OF SPEXIN TREATMENT ON CARDIOMETABOLIC CHANGES IN OBESE TYPE 2 DIABETIC RATS

Background: Spexin is a peptide hormone that was expressed in brain regions and peripheral tissues of many species including human and rat. Several studies investigated its blood level changes with obesity and type 2 diabetes, but few studies assessed its effect on cardiometabolic, histological and morphometric changes in diabetes with some controversies in their results. Objective: To explore the effect of spexin treatment on cardiometabolic, histological and morphometric changes of pancreas and heart tissue in obese type 2 diabetic rats, and the possible mechanisms involved. Materials and Methods: Thirty adult male albino rats were divided randomly into 5 equal groups; control (fed ordinary laboratory chow along this 8 weeks’ study), diabetic [fed high fat diet along this 8 weeks’ study, but at the start of the 4th week, overnight fasted rats were injected with a single streptozotocin injection intraperitoneally (40 mg/kg body weight, dissolved in 0.01M citrate buffer, pH 4.5) to induce diabetes], diabetic metformin-treated [rats were managed as in diabetic group and in addition to that, metformin was given orally (300 mg/kg/day) by oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], diabetic vildagliptin treated [rats were manipulated as in diabetic group and in addition to that, vildagliptin was given orally (10 mg/kg/day) using oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], and diabetic spexin treated [rats were managed as in diabetic group and in addition to that, spexin dissolved in normal saline was injected intraperitoneally (35 μg/kg/day) for 4 weeks from the start of 5th week to the end of 8th week] groups. For histological, immunohistochemical and morphometric examinations, fresh heart and pancreatic specimens were collected from rats that were sacrificed. Results: In diabetic group, a significant increase was detected in final body mass index, serum glucose, serum insulin, homeostasis model assessment-insulin resistance, serum total cholesterol, serum triglycerides, serum low density lipoprotein, atherogenic index, serum dipeptidyl peptidase-IV, serum tumor necrosis factor alpha serum interleukin-1 beta, serum malondialdehyde, serum lactate dehydrogenase, serum creatine kinase-myoglobin binding and mean arterial blood pressure, with a significant decrease in homeostasis model assessment-beta cell functionserum high density lipoprotein, serum superoxide dismutase and serum spexin in comparison to that in the control group. With spexin treatment (as well as with the administration of standard drugs metformin and vildagliptin), all these changes were reversed significantly in comparison with those in the diabetic group. Diabetes induced histopathological changes in cardiac muscle and pancreatic structure which were ameliorated by treatment with spexin as well as with the standard anti-diabetic drugs (metformin and vildagliptin). The morphometric analysis confirmed the histopathological results, as a statistically significant difference was detected in area percent of collagen deposition, area percent of insulin immune-reaction in pancreas and cardiac muscle Bax expression between both diabetic group and all other groups, with no statistically significant difference between diabetic metformin treated, diabetic vildagliptin treated and diabetic spexin treated groups. Conclusion: Spexin ameliorated diabetes induced deleterious cardiometabolic, histopathological and morphometric disturbances. The anti-obesity, dipeptidyl peptidase-IV inhibitory, hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory and cardio-protective properties of spexin may contribute to its useful effects.

EFFECT OF SPEXIN TREATMENT ON CARDIOMETABOLIC CHANGES IN OBESE TYPE 2 DIABETIC RATS

Background: Spexin is a peptide hormone that was expressed in brain regions and peripheral tissues of many species including human and rat. Several studies investigated its blood level changes with obesity and type 2 diabetes, but few studies assessed its effect on cardiometabolic, histological and morphometric changes in diabetes with some controversies in their results. Objective: To explore the effect of spexin treatment on cardiometabolic, histological and morphometric changes of pancreas and heart tissue in obese type 2 diabetic rats, and the possible mechanisms involved. Materials and Methods: Thirty adult male albino rats were divided randomly into 5 equal groups; control (fed ordinary laboratory chow along this 8 weeks’ study), diabetic [fed high fat diet along this 8 weeks’ study, but at the start of the 4th week, overnight fasted rats were injected with a single streptozotocin injection intraperitoneally (40 mg/kg body weight, dissolved in 0.01M citrate buffer, pH 4.5) to induce diabetes], diabetic metformin-treated [rats were managed as in diabetic group and in addition to that, metformin was given orally (300 mg/kg/day) by oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], diabetic vildagliptin treated [rats were manipulated as in diabetic group and in addition to that, vildagliptin was given orally (10 mg/kg/day) using oral gavage to rats for 4 weeks from the start of 5th week to the end of 8th week], and diabetic spexin treated [rats were managed as in diabetic group and in addition to that, spexin dissolved in normal saline was injected intraperitoneally (35 μg/kg/day) for 4 weeks from the start of 5th week to the end of 8th week] groups. For histological, immunohistochemical and morphometric examinations, fresh heart and pancreatic specimens were collected from rats that were sacrificed. Results: In diabetic group, a significant increase was detected in final body mass index, serum glucose, serum insulin, homeostasis model assessment-insulin resistance, serum total cholesterol, serum triglycerides, serum low density lipoprotein, atherogenic index, serum dipeptidyl peptidase-IV, serum tumor necrosis factor alpha serum interleukin-1 beta, serum malondialdehyde, serum lactate dehydrogenase, serum creatine kinase-myoglobin binding and mean arterial blood pressure, with a significant decrease in homeostasis model assessment-beta cell functionserum high density lipoprotein, serum superoxide dismutase and serum spexin in comparison to that in the control group. With spexin treatment (as well as with the administration of standard drugs metformin and vildagliptin), all these changes were reversed significantly in comparison with those in the diabetic group. Diabetes induced histopathological changes in cardiac muscle and pancreatic structure which were ameliorated by treatment with spexin as well as with the standard anti-diabetic drugs (metformin and vildagliptin). The morphometric analysis confirmed the histopathological results, as a statistically significant difference was detected in area percent of collagen deposition, area percent of insulin immune-reaction in pancreas and cardiac muscle Bax expression between both diabetic group and all other groups, with no statistically significant difference between diabetic metformin treated, diabetic vildagliptin treated and diabetic spexin treated groups. Conclusion: Spexin ameliorated diabetes induced deleterious cardiometabolic, histopathological and morphometric disturbances. The anti-obesity, dipeptidyl peptidase-IV inhibitory, hypoglycemic, hypolipidemic, antioxidant, anti-inflammatory and cardio-protective properties of spexin may contribute to its useful effects.

Bioactive Peptides and Hydrolysates from Egg Proteins as a New Tool for Protection Against Cardiovascular Problems.

The aim of the present work is to review the potential beneficial effects of dietary supplementation with bioactive egg protein hydrolysates or peptides on cardiometabolic changes associated with oxidative stress. The development of nutritionally improved food products designed to address specific health concerns is of particular interest because many bioactive food compounds can be potentially useful in various physiological functions such as for reducing oxidative stress. The results presented suggest that egg hydrolysates or derived peptides could be included in the diet to prevent and/or reduce some cardiometabolic complications associated with oxidative stress-related diseases.

Selenoproteins and renal programming in metabolic syndrome-exposed rat offspring.

Maternal metabolic syndrome (MS) during gestation and lactation leads to several cardiometabolic changes related to selenium (Se) status and selenoprotein expression in offspring. However, little is known about kidney programming and antioxidant selenoprotein status in MS pups. To gain more knowledge on this subject, two experimental groups of dam rats were used: Control (Se: 0.1 ppm) and MS (fructose 65% and Se: 0.1 ppm). At the end of lactation, Se deposits in kidneys, selenoprotein expression (GPx1, GPx3, GPx4 and selenoprotein P), oxidative balance and AMP-activated protein kinase (AMPK) and activated transcriptional factor NF-κB expression were measured. Kidney functional parameters, albuminuria, creatinine clearance, aldosteronemia, and water and electrolyte balance, were also evaluated. One week later systolic blood pressure was measured. Lipid peroxidation takes place in the kidneys of MS pups and Se, selenoproteins and NF-κB expression increased, while AMPK activation decreased. MS pups have albuminuria and low creatinine clearance which implies glomerular renal impairment with protein loss. They also present hypernatremia and hyperaldosteronemia, together with a high renal Na+ reabsorption, leading to a hypertensive status, which was detected in these animals one week later. Since these alterations seem to be related, at least in part, to oxidative stress, the increase in Se and selenoproteins found in the kidneys of these pups seems to be beneficial, avoiding a higher lipid oxidation. However, in order to analyze the possible global beneficial role of Se in kidneys during MS exposure, more data are necessary to document the relationships between GPx4 and NF-κB, and SelP and AMPK in kidneys.

Metformin and/or vildagliptin mitigate type II diabetes mellitus induced-oxidative stress: The intriguing effect.

The aim of the present study was to investigate the probable effects of metformin plus vildagliptin on the oxidative stress index (OSI) in patients with type II diabetes mellitus (T2DM). In this case–control study, 44 patients with T2DM on either metformin monotherapy (n = 24) or metformin plus vildagliptin (n = 20) were compared with healthy controls (n = 20). Anthropometric and biochemical variables including body mass index, blood pressure profile, cardiac indices, lipid profile, fasting blood glucose, fasting serum insulin, and glycemic indices were assessed. Besides, total oxidant status (TOS), total antioxidant status (TAS), and OSI were determined. Patients with T2DM have higher risk of cardiometabolic changes compared with the control (P = 0.0001). TAS was lower while TOS and OSI were higher in patients with T2DM, as compared with the healthy controls (P < 0.001). TAS, TOS, and OSI were better in patients with T2DM on metformin plus vildagliptin therapy as compared with metformin monotherapy (P < 0.05). Therefore, this study concluded that metformin plus vildagliptin therapy is more effective than metformin monotherapy in attenuation of OSI in patients with T2DM.