Metabolic Risk Markers Research Articles

Effect of antenatal use of high energy nutritional supplements on cardio metabolic risk markers in underweight primi gravidas; a randomized controlled trial

BackgroudPregnancy is a state of increased metabolic demand, and poor maternal nutrition can exacerbate these changes, potentially increasing the risk of cardiometabolic disorders.This study is significant as it investigates the effect of high energy nutritional supplements on cardio metabolic risk markers in underweight primigravidas.MethodologyA single blinded randomized controlled trial was conducted from April 2018- August 2019 among the Pakistani tertiary care facilities of Khyber Pakhtunkhwa. A total of thirty six participants were randomized into two groups receiving either high energy nutritional supplement ‘MAAMTA’ or Placebo. They were instructed to take Placebo/Supplement alongside to their regular prenatal care and food from their first antenatal visit till a week postnatally. Anthropometric measurements and blood samples for biochemical parameters insulinlevels, fasting blood glucose & lipid profile were taken at baseline visit, between 16 and 20 weeks gestation and a post natal visit.ResultsThe two-way repeated measures ANOVA showed that there was a highly significant time effect on participant’s Insulin level (F (1.8, 53.6) = 10.64, P < 0 0.000, ηp2 = 0.269). A highly significant time effect on participant’s insulin resistance (F (2, 68) = 8.116,P < 0 0.001, ηp2 = 0.193) was also observed. There was a highly significant time effect on participant’s LDL level as well (F (2, 68) = 11.82, P < 0 0.000, ηp2 = 0.258).ConclusionSupplementation with high energy nutritional supplements may improve insulin levels and insulin sensitivity in underweight primigravidas.Trial registrationhttps://www.ClinicalTrials.govClinicalTrials.gov Identifier: ISRCTN 10088578. Registered on 27 March 2018. https://www.isrctn.com/ISRCTN10088578.

Effect of resveratrol supplementation on metabolic risk markers and anthropometric parameters in individuals with obesity or overweight: A systematic review and meta-analysis of randomized controlled trials

BackgroundObesity, a progressively widespread disease with a multifaceted etiology, affects nearly 800 million people worldwide. Recent trials suggest that resveratrol, a polyphenolic compound, can be effective for metabolic risk markers and anthropometric parameters in Individuals with Obesity or Overweight. However, a comprehensive analysis is necessary to consolidate these results. ObjectivesTo evaluate the impact of 4-week resveratrol supplementation on metabolic risk markers and anthropometric parameters in individuals with obesity or overweight. MethodsA comprehensive search was executed across PubMed, Cochrane Library, Scopus, Google Scholar, and clinicaltrials.gov, yielding 43 studies after the omission of 20 duplicates. RevMan 5.4 software was used to statistically analyze randomized controlled studies to gauge the impact of resveratrol on the said outcomes in Individuals with Obesity or Overweight. Quality of bias and potential publication bias were measured using the Cochrane Risk of Bias tool and CMA4 software, respectively. Certainty of the evidence was appraised using GRADEpro software. Data was quantified as the standardized mean difference (SMD) and 95 % confidence intervals (CI). ResultsThe meta-analysis included 5 trials with 419 participants, evaluating the effect of intervention. Resveratrol showed no significant impact on triglycerides (SMD = 0.11, 95%CI [-0.14, 0.35], P = 0.39, I2 = 0 %), total cholesterol (SMD = 0.04, 95%CI [-0.26, 0.33], P = 0.82, I2 = 0 %), or HbA1c (SMD = 0.00, 95%CI [-0.99, 1.00], P = 0.99, I2 = 80 %). Similarly, no significant effect was observed for insulin levels (SMD = −0.00, 95%CI [-0.25, 0.24], P = 0.97, I2 = 0 %), AST (SMD = 0.15, 95%CI [-0.35, 0.65], P = 0.55, I2 = 0 %), or ALT (SMD = −0.03, 95%CI [-0.46, 0.39], P = 0.98, I2 = 0 %). Additionally, resveratrol had no significant effect on BMI (MD = 0.21, 95%CI [-0.970, 1.39], P = 0.70, I2 = 0 %). ConclusionsOur results tagged with p-value>0.05 are an evidence-based indication that resveratrol supplementation does not lead to significant improvements in metabolic or anthropometric parameters. This suggests that resveratrol may not be an effective standalone intervention for managing obesity-related outcomes. Therefore, future research should be redirected to evaluating its potential effects on other health metrics to elucidate its efficacy and therapeutic potential better.

Association Between the Triglyceride-Glucose Index and Serum Uric Acid to High-Density Lipoprotein (HDL) Cholesterol Ratio in Type 2 Diabetes Mellitus in Gabes City, Tunisia.

Background Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases (CVD). The triglyceride-glucoseindex (TyGi) is a novel biomarker for insulin resistance, strongly linked to CVD. Elevated serum uric acid levels and the uric acid to high-density lipoproteincholesterol ratio (UHR) are emerging as markers of metabolic syndrome and cardiovascular risk in T2DM. This study aimed to explore the association between the TyGiand UHR in T2DM patients. Objectives The aim of this study is to compare metabolic parameters in T2DM patients and assess the association between the TyGiand serum UHR. Methodology A cross-sectional case-control study was conducted at the University Hospital of Gabes, Gabes City, Tunisia with 50 T2DM patients and 50 gender-matched healthy controls. Inclusion criteria included adults aged 30-75 years with a confirmed diagnosis of T2DM on stable medication for at least three months. Exclusion criteria included other types of diabetes, significant liver or kidney disease, recent cardiovascular events, endocrine disorders, and substance abuse. Metabolic and biochemical parameters, including fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, lipid profile, and renal function, were measured. The TyGiand serum UHR were calculated and analyzed for correlations. Results T2DM patients exhibited significantly higher fasting blood sugar, postprandial blood sugar, glycosylated hemoglobin, TyGi, and serum UHR compared to controls, indicating impaired glycemic control and adverse lipid profiles. The UHR showed a positive correlation with a strong negative correlation with HDL and a positive correlation with uric acid levels. The linear regression analysis indicated a weak positive trend between the TyGi and serum UHR, although not statistically significant. Conclusion This study underscores the importance of the TyGiand serum UHRas biomarkers for evaluating metabolic and cardiovascular risk in T2DM. Further research is needed to explore their combined utility in clinical practice for early detection and management of cardiovascular complications in diabetic patients.

Transgender healthcare: metabolic outcomes and cardiovascular risk.

Transgender identity is often associated with gender dysphoria and minority stress. Gender-affirming hormone treatment (GAHT) includes masculinising or feminising treatment and is expected to be lifelong in most cases. Sex and sex hormones have a differential effect on metabolism and CVD in cisgender people, and sex hormone replacement in hypogonadism is associated with higher vascular risk, especially in ageing individuals. Using narrative review methods, we present evidence regarding metabolic and cardiovascular outcomes during GAHT and propose recommendations for follow-up and monitoring of metabolic and cardiovascular risk markers during GAHT. Available data show no increased risk for type 2 diabetes in transgender cohorts, but masculinising GAHT increases lean body mass and feminising GAHT is associated with higher fat mass and insulin resistance. The risk of CVD is increased in transgender cohorts, especially during feminising GAHT. Masculinising GAHT is associated with a more adverse lipid profile, higher haematocrit and increased BP, while feminising GAHT is associated with pro-coagulant changes and lower HDL-cholesterol. Assigned male sex at birth, higher age at initiation of GAHT and use of cyproterone acetate are separate risk factors for adverse CVD markers. Metabolic and CVD outcomes may improve during gender-affirming care due to a reduction in minority stress, improved lifestyle and closer surveillance leading to optimised preventive medication (e.g. statins). GAHT should be individualised according to individual risk factors (i.e. drug, dose and form of administration); furthermore, doctors need to discuss lifestyle and preventive medications in order to modify metabolic and CVD risk during GAHT. Follow-up programmes must address the usual cardiovascular risk markers but should consider that biological age and sex may influence individual risk profiling including mental health, lifestyle and novel cardiovascular risk markers during GAHT.

Abnormal blood pressure and pediatric obesity phenotype: Red flags for clinical practice

Background and aimssystolic and diastolic blood pressure values identify different subtypes of Primary Hypertension. In pediatric age, hypertension is often related to obesity. Characterization of an individual's Blood Pressure (BP) status needs multiple measurements in the course of time, but this is rarely the case, principally in everyday pediatrics. Thus, the finding of abnormal BP values even in a single routine check visit should need a special attention. The aim of this study was to evaluate if even a single abnormal measurement could be a marker of metabolic risk, according to clinical and/or metabolic phenotype and subtypes of hypertension in a population of overweight/obese children and adolescents. Methods and resultsWe reviewed data from 489 overweight-obese children and adolescents. BP values were classified according to American Academy of Pediatrics Guidelines (2017). Considering study design, we used the term “Abnormal” instead of “High” BP. Data on lipid profile, glucose metabolism and ultrasonographic pattern of the liver were recorded. Mean age was 9.4 ± 2.5 years: 76.9% had normal BP values. Children with Abnormal BP harbored more frequently an unfavorable metabolic profile. Children with Abnormal Systolic-Diastolic BP values had higher BMI z-score and Waist to Height ratio (p = 0.022 and p = 0.032). Hepatic Steatosis was detected in 4.5%, 14.8 % and 17.6 % of children with normal, abnormal systolic and abnormal systo-diastolic blood pressure, respectively. (p < 0.001). ConclusionIdentification of abnormal BP subtypes even in a single measurement could be useful for identification of specific clinical-metabolic phenotypes allowing an individual targeted management of obesity-related comorbidities.

Daily standing time, dietary fiber, and intake of unsaturated fatty acids are beneficially associated with hepatic insulin sensitivity in adults with metabolic syndrome.

Obesity is associated with impaired glucose metabolism and hepatic insulin resistance. The aim was to investigate the associations of hepatic glucose uptake (HGU) and endogenous glucose production (EGP) to sedentary behavior (SB), physical activity (PA), cardiorespiratory fitness, dietary factors, and metabolic risk markers. Forty-four adults with metabolic syndrome (mean age 58 [SD 7] years, BMI ranging from 25-40kg/; 25 females) were included. HGU was measured by positron emission tomography during the hyperinsulinemic-euglycemic clamp. EGP was calculated by subtracting the glucose infusion rate during clamp from the glucose rate of disappearance. SB and PA were measured with hip-worn accelerometers (26 [SD3] days). Fitness was assessed by maximal bicycle ergometry with respiratory gas measurements and dietary intake of nutrients by 4-day food diaries. HGU was not associated with fitness or any of the SB or PA measures. When adjusted for sex, age, and body fat-%, HGU was associated with whole-body insulin sensitivity (β=0.58), water-insoluble dietary fiber (β=0.29), energy percent (E%) of carbohydrates (β=-0.32), saccharose (β=-0.32), mono- and polyunsaturated fatty acids (β=0.35, β=0.41, respectively). EGP was associated with whole-body insulin sensitivity (β=-0.53), and low-density lipoprotein cholesterol [β=-0.31], and when further adjusted for accelerometry wear time, EGP was associated with standing [β=-0.43]. (p-value for all< 0.05). Standing more, consuming a diet rich in fiber and unsaturated fatty acids, and a lower intake of carbohydrates, especially sugar, associate beneficially with hepatic insulin sensitivity. Habitual SB, PA, or fitness may not be the primary modulators of HGU and EGP. However, these associations need to be confirmed with intervention studies.

Untargeted lipidomics analysis in women with morbid obesity and type 2 diabetes mellitus: A comprehensive study.

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women.

Increased plasminogen activator inhibitor-1 (PAI-1) and its associations with metabolic risk in healthy young adults with early life stress

ObjectivesWe aimed to characterize the interplay between early life stress (ELS), metabolic syndrome (MetS), and plasminogen activator inhibitor-1 (PAI-1), a major inhibitor of the fibrinolytic system implicated in cardiometabolic diseases. We also examined the understudied intersection of ELS, physical activity and PAI-1. MethodsHealthy young adults ages 18–40 (N=200; 68% female) were recruited from the community. Participants with ELS (N=118) experienced childhood maltreatment, and the majority (n=92) also experienced childhood parental loss. Control participants (N=82) had no history of childhood maltreatment or parental loss. Participants had no current cardiometabolic or thrombotic conditions. Fasting plasma samples were assessed for markers of metabolic risk and total PAI-1 using the Bio-Plex Pro Human Diabetes Panel (Bio-Rad Laboratories). A composite metabolic risk z-score (MetS risk) was computed from the mean standardized z-scores of waist-to-height ratio, systolic and diastolic blood pressure, triglycerides, total cholesterol, LDL and HLD cholesterol, fasting plasma glucose, and hemoglobin A1c. ResultsWe found that a history of ELS was linked to both higher PAI-1 levels and a higher MetS risk score. ELS was associated with a higher MetS Z-score in adulthood via increased circulating PAI-1 levels (Average Causal Mediation Effect [ACME]= 0.07, p = 0.036). ELS was also linked to increased PAI-1 levels via greater MetS z-scores (ACME = 0.02, p < 0.001). There was a significant interaction effect of ELS and exercise on PAI-1 levels (p = 0.03), such that engaging in higher levels of daily exercise was linked to lower PAI-1 levels in individuals with ELS. ConclusionHealthy young adults with ELS have elevated PAI-1 levels and metabolic risk scores. Among individuals with ELS, exercise is linked to lower PAI-1 levels, suggesting a potential direction for early intervention.

Glucose tolerance and insulin resistance/sensitivity associate with retinal layer characteristics: the LIFE-Adult-Study

Aims/hypothesisAs the prevalence of insulin resistance and glucose intolerance is increasing throughout the world, diabetes-induced eye diseases are a global health burden. We aim to identify distinct optical bands which are closely related to insulin and glucose metabolism, using non-invasive, high-resolution spectral domain optical coherence tomography (SD-OCT) in a large, population-based dataset.MethodsThe LIFE-Adult-Study randomly selected 10,000 participants from the population registry of Leipzig, Germany. Cross-sectional, standardised phenotyping included the assessment of various metabolic risk markers and ocular imaging, such as SD-OCT-derived thicknesses of ten optical bands of the retina. Global and Early Treatment Diabetic Retinopathy Study (ETDRS) subfield-specific optical retinal layer thicknesses were investigated in 7384 healthy eyes of 7384 participants from the LIFE-Adult-Study stratified by normal glucose tolerance, prediabetes (impaired fasting glucose and/or impaired glucose tolerance and/or HbA1c 5.7–6.4% [39–47 mmol/mol]) and diabetes. The association of optical retinal band characteristics with different indices of glucose tolerance (e.g. fasting glucose, area under the glucose curve), insulin resistance (e.g. HOMA2-IR, triglyceride glucose index), or insulin sensitivity (e.g. estimated glucose disposal rate [eGDR], Stumvoll metabolic clearance rate) was determined using multivariable linear regression analyses for the individual markers adjusted for age, sex and refraction. Various sensitivity analyses were performed to validate the observed findings.ResultsIn the study cohort, nine out of ten optical bands of the retina showed significant sex- and glucose tolerance-dependent differences in band thicknesses. Multivariable linear regression analyses revealed a significant, independent, and inverse association between markers of glucose intolerance and insulin resistance (e.g. HOMA2-IR) with the thickness of the optical bands representing the anatomical retinal outer nuclear layer (ONL, standardised β=−0.096; p<0.001 for HOMA2-IR) and myoid zone (MZ; β=−0.096; p<0.001 for HOMA2-IR) of the photoreceptors. Conversely, markers of insulin sensitivity (e.g. eGDR) positively and independently associated with ONL (β=0.090; p<0.001 for eGDR) and MZ (β=0.133; p<0.001 for eGDR) band thicknesses. These global associations were confirmed in ETDRS subfield-specific analyses. Sensitivity analyses further validated our findings when physical activity, neuroanatomical cell/tissue types and ETDRS subfield categories were investigated after stratifying the cohort by glucose homeostasis.Conclusions/interpretationAn impaired glucose homeostasis associates with a thinning of the optical bands of retinal ONL and photoreceptor MZ. Changes in ONL and MZ thicknesses might predict early metabolic retinal alterations in diabetes.Graphical

Association between serum trace element, mineral, and amino acid levels with non-alcoholic fatty liver disease (NAFLD) in adult women

The objective of the present study is assessment of serum trace element and amino acid levels in non-alcoholic fatty liver disease (NAFLD) patients with subsequent evaluation of its independent associations with markers of liver injury and metabolic risk. Materials and methods140 women aged 20–90 years old with diagnosed NAFLD and 140 healthy women with a respective age range were enrolled in the current study. Analysis of serum and hair levels of trace elements and minerals was performed with inductively-coupled plasma mass-spectrometry (ICP-MS). Serum amino acid concentrations were evaluated by high-pressure liquid chromatography (HPLC) with UV-detection. In addition, routine biochemical parameters including liver damage markers, alanine aminotransferase (ALT) and gamma-glutamyltransferase (GGT), were assessed spectrophotometrically. ResultsThe findings demonstrated that patients with NAFLD were characterized by higher ALT, GGT, lactate dehydrogenase (LDH) and cholinesterase (CE) activity, as well as increased levels of total cholesterol, low-density lipoprotein cholesterol, triglycerides, and uric acid. NAFLD patients were characterized by reduced serum and hair Co, Se, and Zn levels, as well as hair Cu content and serum Mn concentrations in comparison to controls. Circulating Ala, Cit, Glu, Gly, Ile, Leu, Phe, and Tyr levels in NAFLD patients exceeded those in the control group. Multiple linear regression demonstrated that serum and hair trace element levels were significantly associated with circulating amino acid levels after adjustment for age, BMI, and metabolic parameters including liver damage markers. ConclusionIt is proposed that altered trace element handling may contribute to NAFLD pathogenesis through modulation of amino acid metabolism.

Reduced HDL-cholesterol in long COVID-19: A key metabolic risk factor tied to disease severity

This controlled study investigated metabolic changes in non-vaccinated individuals with Long-COVID-19, along with their connection to the severity of the disease. The study involved 88 patients who experienced varying levels of initial disease severity (mild, moderate, and severe), and a control group of 29 healthy individuals. Metabolic risk markers from fasting blood samples were analyzed, and data regarding disease severity indicators were collected. Findings indicated significant metabolic shifts in severe Long-COVID-19 cases, mainly a marked drop in HDL-C levels and a doubled increase in ferritin levels and insulin resistance compared to the mild cases and controls. HDL-C and ferritin were identified as the leading factors predicted by disease severity. In conclusion, the decline in HDL-C levels and rise in ferritin levels seen in Long-COVID-19 individuals, largely influenced by the severity of the initial infection, could potentially play a role in the persistence and progression of Long-COVID-19. Hence, these markers could be considered as possible therapeutic targets, and help shape preventive strategies to reduce the long-term impacts of the disease.

Correlation between Dyslipedemia and Urine Albumin Excretion in Non Diabetic Obese Subjects: A Cross-sectional Study

Introduction: Obesity is a global health concern, and recent research has shown that it can cause kidney problems, especially in non diabetics. Obesity-related dyslipedemia, characterised by aberrant lipid profiles, may contribute to kidney damage. Aim: The purpose of the present cross-sectional study was to shed light on the complex interaction between dyslipedemia and renal health by examining the relationship between dyslipedemia and urine albumin excretion in non diabetic obese adults. Materials and Methods: The cross-sectional investigation was conducted in the Outpatient Obesity Clinic of the Endocrinology Department at a Tertiary Hospital in Kerala, India. A total of 144 non diabetic obese individuals between the ages of 18 and 65 years. All subjects provided informed consent, and ethical approval was obtained. The primary inclusion criteria were a Body Mass Index (BMI) of less than 25.0, the absence of Type 2 Diabetes Mellitus (T2DM), and the absence of proteinuria. Urine and blood samples were collected for laboratory testing, and statistical analysis was conducted using International Business Machines (IBM) Statistical Package for Social Sciences (SPSS) Statistics 20.0. Results: Dyslipedemia was found to be common, with low High-Density Lipoproteins (HDL) levels in 41.4% of participants, high Low-Density Lipoproteins (LDL) levels in 49.6%, high Triglycerides (TG) levels in 29.7%, and high Total Cholesterol (TC) levels in 43%. The study revealed that obese individuals with dyslipedemia excrete albumin at a significantly higher rate than obese individuals without dyslipedemia. Furthermore, a weak correlation between TG levels and the Urine Albumin Creatinine Ratio (UACR) was discovered. However, UACR did not significantly correlate with metabolic risk markers such as Fasting Plasma Glucose (FPG), serum insulin, blood pressure, HDL, LDL, TC, and systolic/Diastolic Blood Pressure (DBP). Conclusion: The results of the present study demonstrate that dyslipedemia significantly contributes to kidney damage in non diabetic obese individuals. The presence of dyslipedemia in obese then could serve as an early warning sign of potential renal problems. Further research is needed to fully understand the complex interactions between obesity, dyslipedemia, and renal health. These insights could be crucial for developing effective preventative and intervention methods in this context.

The effect of dairy products on liver fat and metabolic risk markers in males with abdominal obesity – a four-arm randomized controlled trial

In recent years, epidemiological studies have reported links between the consumption of fermented dairy products, such as yogurt, and health; however, evidence from human intervention trials is scarce and inconsistent. We aimed to investigate the effect of consumption of four different types of dairy products (two fermented and two non-fermented) on liver fat (primary outcome) and metabolic risk markers in males with abdominal obesity. In this parallel randomized controlled trial with four arms, 100 males aged 30-70 years, with body mass index 28.0-45.0kg/m2, and waist circumference ≥102cm underwent a 16-weeks intervention where they were instructed to consume 400g/day of either milk, yogurt, heat-treated yogurt, or acidified milk as part of their habitual diet. Liver fat was measured by magnetic resonance imaging. In the complete case analyses (n=80), no effects of the intervention or differences between groups were detected in anthropometry or body composition including liver fat. Moreover, no effects were detected in inflammatory markers. Main effects of time were detected in blood pressure (decrease; P<0.001), insulin (decrease; P<0.001), C-peptide (decrease; P=0.040), homeostatic model assessment for insulin resistance (decrease; P<0.001), total cholesterol (decrease; P=0.016), low-density lipoprotein (decrease; P=0.033), high-density lipoprotein (decrease; P=0.006), and alanine transaminase (decrease; P=0.019). Interactions between group and time failed to reach significance. In conclusion, findings from our study do not confirm that fermented yogurt products are superior in reducing liver fat or improving metabolic risk markers compared to non-fermented milk products. In fact, all intervention products (both fermented yogurt products and non-fermented milk products) did not affect liver fat and caused largely similar modest favorable changes in some metabolic risk markers. The study was registered at www. gov (# NCT04755530).

Human cord plasma proteomic analysis reveals sexually dimorphic proteins associated with intrauterine growth restriction.

Intrauterine growth restriction (IUGR) is associated with increased risk of cardiometabolic disease later in life and has been shown to affect female and male offspring differently, but the mechanisms remain unclear. The purpose of this study was to identify proteomic differences and metabolic risk markers in IUGR male and female neonates when compared to appropriate for gestational age (AGA) babies that will provide a better understanding of IUGR pathogenesis and its associated risks. Our results revealed alterations in IUGR cord plasma proteomes with most of the differentially abundant proteins implicated in peroxisome pathways. This effect was evident in females but not in males. Furthermore, we observed that catalase activity, a peroxisomal enzyme, was significantly increased in females (p<0.05) but unchanged in males. Finally, we identified risk proteins associated with obesity, type-2 diabetes, and glucose intolerance such as EGF containing fibulin extracellular matrix protein 1 (EFEMP1), proprotein convertase subtilisin/kexin type 9 (PCSK9) and transforming growth factor beta receptor 3 (TGFBR3) proteins unique to females while coagulation factor IX (C9) and retinol binding protein 4 (RBP4) are unique in males. In conclusion, IUGR may display sexual dimorphism which may be associated with differences in lifelong risk for cardiometabolic disease between males and females.

The association of copeptin with metabolic risk markers is modified by region of origin

Iraqi born immigrants in Sweden have higher prevalence of metabolic diseases compared to native Swedes. Copeptin, a marker for vasopressin, is associated with increased risk of metabolic disease. In this cross-sectional population study based on the MEDIM cohort we investigated differences in copeptin levels between Iraqi and Swedish born individuals and if the association between copeptin and cardiometabolic risk markers differed by region of origin. We included 1109 Iraqi and 613 Swedish born participants (58% men, mean age 47 years). The Swedish participants had a higher concentration of copeptin compared to the Iraqi born group after age and sex adjustment (p < 0.001). This difference existed only among male individuals with the highest copeptin concentrations, i.e. belonging to copeptin quartile 4 (median (25th; 75th percentile) 20.07 (15.27;33.28) pmol/L for the Swedish born versus 15.57 (13.91;19.00) pmol/L for the Iraqi born, p < 0.001). We found a significant interaction between copeptin (continuous ln-transformed) and being born in Iraq regarding the association with plasma triglycerides (Pinteraction = 0.006). The association between copeptin and BMI was stronger amongst the Iraqi born individuals compared to the Swedish born. Together, this could indicate that copeptin is a more potent marker of metabolic disease among individuals born in Iraq compared to Sweden.

Non-invasive omics analysis delineates molecular changes in water-only fasting and its sex-discriminating features in metabolic syndrome patients.

Fasting has been grown in popularity with multiple potential benefits. However, very few studies dynamically monitor physiological and pathological changes during long-term fasting using noninvasive methods. In the present study, we recruited 37 individuals with metabolic syndrome to engage in a 5-day water-only fasting regimen, and simultaneously captured the molecular alterations through urinary proteomics and metabolomics. Our findings reveal that water-only fasting significantly mitigated metabolic syndrome-related risk markers, such as body weight, body mass index, abdominal circumference, blood pressure, and fasting blood glucose levels in metabolic syndrome patients. Indicators of liver and renal function remained within the normal range, with the exception of uric acid. Notably, inflammatory response was inhibited during the water-only fasting period, as evidenced by a decrease in the human monocyte differentiation antigen CD14. Intriguingly, glycolysis, tricarboxylic acid cycle, and oxidative phosphorylation underwent a sex-dependent reprogramming throughout the fasting period, whereby males exhibited a greater upregulation of carbohydrate metabolism-related enzymes than females. This disparity may be attributed to evolutionary pressures. Collectively, our study sheds light on the beneficial physiological effects and novel dynamic molecular features associated with fasting in individuals with metabolic syndrome using noninvasive methods.

Non-Alcoholic fatty liver disease and metabolic syndrome in patients with HIV/AIDS and its correlation with antiretroviral therapy and severity of disease

Introduction: Metabolic syndrome (MetS) and Non-alcoholic fatty liver disease (NAFLD) are two major causes of morbidity in chronic HIV infected patients on antiretroviral therapy (ART). This study was done on HIV infected individuals by comparing ART naive patients with patients on different ART regimens and evaluating the effect of ART on Metabolic syndrome and NAFLD.Method: It was a cross-sectional observational study done on 120 HIV infected individuals in a tertiary care centre in New Delhi. All cases with hypertension, diabetes, chronic kidney or liver disease, thyroid disorders or on any drugs except ART were excluded. The risk markers for metabolic syndrome were assessed and compared within groups on different ART regimens.Results: Metabolic syndrome and NAFLD were found to be significantly more in cases on ART as compared to ART naïve cases. Metabolic syndrome was found to be associated with type of ART protease inhibitors (ATV/r)&gt; nonucleoside reverse transcriptase inhibitors (NNRTI) &gt; no ART] and low CD4 cell counts (p=0.01). In those patients who were on ART, these parameters were found to be more in those on second line ART [i.e., protease inhibitor (PI)(ATV/r) based regimens] as compared to those on first line ART, [i.e., nonnucleoside reverse transcriptase inhibitors (NNRTI) based regimen]. 15% of cases on 2nd line ART (group C) had MetS as compared to 12.5% in those on 1st line ART (group B) and nil in ART naïve cases (group A). One third (34%) of all 120 cases were found to have NAFLD. A significantly higher number of cases (45%) in group C had NAFLD as compared to 32.5% in group B and 25% in group A respectively. Insulin resistance and metabolic risk markers were also significantly higher in cases on ART as compared to ART naïve.Conclusions: In HIV patients, the use of antiretroviral therapy (ART) is linked to an increase in the prevalence of metabolic risk factors, including insulin resistance, lipoatrophy and dystrophy, dyslipidaemia, and abnormalities of fat distribution. Although care of Opportunistic infections and recently CVD has received a lot of attention, it is equally important to address the metabolic abnormalities such as metabolic syndrome and NAFLD brought on by ART.

P-648 Association of severity of menstrual dysfunction with cardiometabolic risk markers in polycystic ovary syndrome

Abstract Study question Is the severity of menstrual dysfunction related to cardiometabolic risk markers in women with polycystic ovary syndrome (PCOS)? Summary answer PCOS women with amenorrhea, compared to those with oligomenorrhea or eumenorrhea, show a higher prevalence of insulin resistance (IR), prediabetes and hypertriglyceridemia. What is known already PCOS is associated robustly with a wide range of unfavorable cardiometabolic risk markers, including obesity, glucolipid metabolism disorders and metabolic syndrome. Many epidemiological studies have found compared to the women with regular menstrual cycles, women with a history of irregular menstruation increased the risks of metabolic syndrome and coronary heart disease. Recently, the association between the severity of menstrual cyclicity and hyperinsulinemia and IR has been demonstrated, suggesting menstrual history could be a simple but clinically important marker of metabolic dysfunction risk. But evidence linking the severity of menstrual cyclicity with cardiometabolic risk in PCOS women is very limited. Study design, size, duration In this prospective cross-sectional study, one hundred and fifty-four women diagnosed with PCOS by the Rotterdam criteria were recruited from July 2021 to September 2022. The association of menstrual cycle regularity with cardiometabolic risk markers including obesity, hypertension, glycemic abnormalities, dyslipidemia and metabolic syndrome was systematically analyzed. Participants/materials, setting, methods In a university-affiliated hospital, PCOS participants with eumenorrheic (Eumeno, n = 24), oligomenorrhea (Oligo, n = 73) and amenorrhea (Ameno, n = 57) underwent history and physical examination, gonadal steroid hormone measurement, lipid profile, oral glucose tolerance test (OGTT) and homeostasis model assessment of IR. Main results and the role of chance Adjusting for age, BMI and waist circumference, a trend toward an increase of unfavorable cardiometabolic risk markers including obesity, hypertension, prevalence of IR, prediabetes, hypertriglyceridemia and prevalence of metabolic syndrome was observed in Ameno group than in other menstrual categories. A significantly higher prevalence of IR, prediabetes and hypertriglyceridemia was demonstrated in Ameno group compared to the Eumeno or Oligo group. In logistic regression, adjusting for age, BMI, and waist circumference, Ameno women were more likely to have: IR than Eumeno women (odds ratio [OR]: 2.90; 95% CI: 1.01 to 8.31); prediabetes than Eumeno women (OR: 4.06; 95% CI: 1.05 to 15.77) and hypertriglyceridemia than Oligo women (OR: 4.43; 95% CI: 1.74 to 11.26). Moreover, the prevalence of IR, prediabetes and hypertriglyceridemia was still significantly higher in Ameno group than that in the Oligo or Eumeno group when further adjusted for free androgen index in the logistic regression. The proportion of Type 2 Diabetes, high total cholesterol, high low-density lipoprotein (LDL) cholesterol and low high-density lipoprotein (HDL) cholesterol was similar across the three groups. Limitations, reasons for caution Our study was limited by its cross-sectional nature, and another limitation was the cycle regularity question relied on the participant’s interpretation of irregular, although we have acquired the detailed menstrual cycle history and further reviewed at consultation, yet some exposure misclassification might also be present. Wider implications of the findings Our study used menstrual cycle as a readily obtainable marker for identification of PCOS women at greatest risk of IR, prediabetes and hypertriglyceridemia, which would emphasize the importance of menstrual cycle regularity and help refine the current recommendations concerning the screening of PCOS subjects for cardiometabolic diesases. Trial registration number 20210728

THE POLYMORPHISM -308 G/A OF THE TNF GENE AND METABOLIC IMBALANCE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE, TAKING INTO ACCOUNT CARDIOVASCULAR COMPLICATIONS

Non-alcoholic fatty liver disease (NAFLD), the most common form of liver disease, is now recognized as a major public health problem worldwide. Tumor necrosis factor alfa (TNF-α), a member of the TNF/TNFR cytokine family, is an intercellular transmission molecule that has been reported in a wide range of human noninfection diseases. The aim of the study was to determine the circulating levels of TNF-α and the nature of its relationships with the components of insulin resistance, both metabolic and hormonal, in patients with type 2 diabetes; and establishing the nature of cardiovascular complications (taking into account TNF-α gene polymorphism) in the presence and absence of NAFLD. Materials and methods. Case-control study included information about 50 practically healthy people from the city of Kharkiv and the region. The examined population (except control subjects) consisted exclusively of patients with type 2 diabetes mellitus with a long-term existence of the disease against the background of metabolic syndrome, with varying degrees of glycemic control and violations of liver homeostasis in the absence of renal failure. 117 people were selected for analysis: 63 of them with type 2 diabetes in the presence of NAFLD and 54 patients with type 2 diabetes without NAFLD. Genotyping for single nucleotide polymorphism -308 G&gt;A of the TNF-α was performed by the method of polymerase chain reaction with appropriate primers and NcoI endonuclease. Testing of statistical hypotheses was carried out using the odds ratio and χ2 criteria at the significance level of P≤0.05. Results. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G&gt;A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus. No association of the studied polymorphism with the risk of developing NAFLD was found. The obtained data make it possible to assume that the studied polymorphism -308 G&gt;A of the TNFα gene is more associated with the risk of developing type 2 diabetes, and the occurrence or progression of NAFLD primarily depends on metabolic imbalance, and not on the contribution of the studied polymorphism. Conclusions. Non-alcoholic fatty liver disease is closely related to hormonal and metabolic risk factors and markers of cardiovascular disease and type 2 diabetes and may increase the risk of developing and progressing cardiovascular complications. The contribution of the genetic component to the formation of the predisposition to the development of type 2 diabetes mellitus based on the single-nucleotide polymorphism -308 G&gt;A of the TNFα gene was determined, which makes it possible to consider the carrier of the A allele as a factor of increased risk for the development of type 2 diabetes mellitus.

Sweet treats before sleep disrupt the clock system and increase metabolic risk markers in healthy rats.

Biological rhythms are endogenously generated natural cycles that act as pacemakers of different physiological mechanisms and homeostasis in the organism, and whose disruption increases metabolic risk. The circadian rhythm is not only reset by light but it is also regulated by behavioral cues such as timing of food intake. This study investigates whether the chronic consumption of a sweet treat before sleeping can disrupt diurnal rhythmicity and metabolism in healthy rats. For this, 32 Fischer rats were administered daily a low dose of sugar (160 mg/kg, equivalent to 2.5 g in humans) as a sweet treat at 8:00 a.m. or 8:00 p.m. (ZT0 and ZT12, respectively) for 4 weeks. To elucidate diurnal rhythmicity of clock gene expression and metabolic parameters, animals were sacrificed at different times, including 1, 7, 13, and 19 h after the last sugar dose (ZT1, ZT7, ZT13, and ZT19). Increased body weight gain and higher cardiometabolic risk were observed when sweet treat was administered at the beginning of the resting period. Moreover, central clock and food intake signaling genes varied depending on snack time. Specifically, the hypothalamic expression of Nampt, Bmal1, Rev-erbα, and Cart showed prominent changes in their diurnal expression pattern, highlighting that sweet treat before bedtime disrupts hypothalamic control of energy homeostasis. These results show that central clock genes and metabolic effects following a low dose of sugar are strongly time-dependent, causing higher circadian metabolic disruption when it is consumed at the beginning of the resting period, that is, with the late-night snack.