A proposed simplified definition of metabolic syndrome in children and adolescents: a global perspective.

Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice.We proposed a simplified definition for assessing MetS risk in youths aged 6-17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89-0.92) and 0.79 (0.78-0.81) when using the IDF or NCEP definition as the gold standard, respectively.The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Establishing international optimal cut-offs of waist-to-height ratio for predicting cardiometabolic risk in children and adolescents aged 6-18 years.

BACKGROUND: Waist-to-height ratio (WHtR) has been proposed as a simple and effective screening tool for assessing central obesity and cardiometabolic risk in both adult and pediatric populations. However, evidence suggests that the use of a uniform WHtR cut-off of 0.50 may not be universally optimal for pediatric populations globally. We aimed to determine the optimal cut-offs of WHtR in children and adolescents with increased cardiometabolic risk across different countries worldwide. METHODS: We used ten population-based cross-sectional data on 24,605 children and adolescents aged 6-18 years from Brazil, China, Greece, Iran, Italy, Korea, South Africa, Spain, the UK, and the USA for establishing optimal WHtR cut-offs. We performed an external independent test (9,619 children and adolescents aged 6-18 years who came from other six countries) to validate the optimal WHtR cut-offs based on the predicting performance for at least two or three cardiometabolic risk factors. RESULTS: Based on receiver operator characteristic curve analyses of various WHtR cut-offs to discriminate those with ≥ 2 cardiometabolic risk factors, the relatively optimal percentile cut-offs of WHtR in the normal weight subsample population in each country did not always coincide with a single fixed percentile, but varied from the 75th to 95th percentiles across the ten countries. However, these relatively optimal percentile values tended to cluster irrespective of sex, metabolic syndrome (MetS) criteria used, and WC measurement position. In general, using ≥ 2 cardiometabolic risk factors as the predictive outcome, the relatively optimal WHtR cut-off was around 0.50 in European and the US youths but was lower, around 0.46, in Asian, African, and South American youths. Secondary analyses that directly tested WHtR values ranging from 0.42 to 0.56 at 0.01 increments largely confirmed the results of the main analyses. In addition, the proposed cut-offs of 0.50 and 0.46 for two specific pediatric populations, respectively, showed a good performance in predicting ≥ 2 or ≥ 3 cardiometabolic risk factors in external independent test populations from six countries (Brazil, China, Germany, Italy, Korea, and the USA). CONCLUSIONS: The proposed international WHtR cut-offs are easy and useful to identify central obesity and cardiometabolic risk in children and adolescents globally, thus allowing international comparison across populations.

MicroRNAs Associated with Chronic Kidney Disease in the General Population and High-Risk Subgroups-A Systematic Review.

The potential utility of microRNAs (miRNAs) as diagnostic or prognostic biomarkers, as well as therapeutic targets, for chronic kidney disease (CKD) has been advocated. However, studies evaluating the expression profile of the same miRNA signatures in CKD report contradictory findings. This review aimed to characterize miRNAs associated with CKD and/or measures of kidney function and kidney damage in the general population, and also in high-risk subgroups, including people with hypertension (HTN), diabetes mellitus (DM) and human immunodeficiency virus (HIV) infection. Medline via PubMed, Scopus, Web of Science, and EBSCOhost databases were searched to identify relevant studies published in English or French languages on or before 30 September 2022. A total of 75 studies fulfilled the eligibility criteria: CKD (n = 18), diabetic kidney disease (DKD) (n = 51) and HTN-associated CKD (n = 6), with no study reporting on miRNA profiles in people with HIV-associated nephropathy. In individuals with CKD, miR-126 and miR-223 were consistently downregulated, whilst in DKD, miR-21 and miR-29b were consistently upregulated and miR-30e and let-7a were consistently downregulated in at least three studies. These findings suggest that these miRNAs may be involved in the pathogenesis of CKD and therefore invites further research to explore their clinical utility for CKD prevention and control.

Two novel microRNAs and their association with absolute blood pressure parameters in an urban South African community.

MicroRNAs are important in development of disease, and description of novel microRNAs adds to the pool of microRNAs that can be targeted for diagnostic and therapeutic purposes in disease. Herein, we aimed to describe novel microRNAs in a normotensive and hypertensive African population and relate their expression to blood pressure parameters and hypertension status. Previous work using next-generation sequencing showed differential expression of two novel microRNAs in the blood of normotensives and hypertensives. Herein, we have investigated these novel microRNAs by quantitative reverse transcription polymerase chain reaction in a cohort of 881 participants in this study. The relationship between the novel microRNAs and systolic and diastolic blood pressure as well as mean arterial pressure was also investigated. Age and sex-adjusted Spearman's correlations were used to assess the relationship between microRNAs and cardiovascular risk profile variables whilst multivariable logistic regression models were used to assess the association of microRNAs with screen-detected and known hypertension. The novel microRNAs (miR-novel-chr1_36178 and miR-novel-chr15_18383) were significantly dysregulated by hypertension status. The expression of miR-novel-chr1_36178 differed according to sex, correlated with mean arterial pressure and systolic and diastolic blood pressure at higher levels of expression and was associated with screen-detected hypertension. The association of miR-novel-chr1_36178 expression with mean arterial pressure and systolic and diastolic blood pressure, as well as its dysregulation according to hypertension status suggests its possible utility as a biomarker target for hypertension diagnosis and/or therapeutics. Furthermore, its association with screen detected hypertension and dose-response relationship with blood pressure suggests it may be used to identify and monitor individuals at risk of hypertension.

The agreement between fasting glucose and markers of chronic glycaemic exposure in individuals with and without chronic kidney disease: a cross-sectional study.

BACKGROUND: To assess whether the agreement between fasting glucose and glycated proteins is affected by chronic kidney disease (CKD) in a community-based sample of 1621 mixed-ancestry South Africans. METHODS: CKD was defined as an estimated glomerular filtration rate < 60 ml/min/1.73 m2. Fasting plasma glucose and haemoglobin A1c (HbA1c) concentrations were measured by enzymatic hexokinase method and high-performance liquid chromatography, respectively, with fructosamine and glycated albumin measured by immunoturbidimetry and enzymatic method, respectively. RESULTS: Of those with CKD (n = 96), 79, 16 and 5% where in stages 3, 4 and 5, respectively. Those with CKD had higher levels of HbA1c (6.2 vs. 5.7%; p < 0.0001), glycated albumin (15.0 vs. 13.0%; p < 0.0001) and fructosamine levels (269.7 vs. 236.4 µmol/l; p < 0.0001), compared to those without CKD. Higher fasting glucose levels were associated with higher HbA1c, glycated albumin and fructosamine, independent of age, gender, and CKD. However, the association with HbA1c and glycated albumin differed by CKD status, at the upper concentrations of the respective markers (interaction term for both: p ≤ 0.095). CONCLUSION: Our results suggest that although HbA1c and glycated albumin perform acceptably under conditions of normoglycaemia, these markers correlate less well with blood glucose levels in people with CKD who are not on dialysis.

An African perspective on the genetic risk of chronic kidney disease: a systematic review.

BACKGROUND: Individuals of African ethnicity are disproportionately burdened with chronic kidney disease (CKD). However, despite the genetic link, genetic association studies of CKD in African populations are lacking. METHODS: We conducted a systematic review to critically evaluate the existing studies on CKD genetic risk inferred by polymorphism(s) amongst African populations in Africa. The study followed the HuGE handbook and PRISMA protocol. We included studies reporting on the association of polymorphism(s) with prevalent CKD, end-stage renaldisease (ESRD) or CKD-associated traits. Given the very few studies investigating the effects of the same single nucleotide polymorphisms (SNPs) on CKD risk, a narrative synthesis of the evidence was conducted. RESULTS: A total of 30 polymorphisms in 11 genes were investigated for their association with CKD, ESRD or related traits, all using the candidate-gene approach. Of all the included genes, MYH9, AT1R and MTHFR genes failed to predict CKD or related traits, while variants in the APOL1, apoE, eNOS, XPD, XRCC1, renalase, ADIPOQ, and CCR2 genes were associated with CKD or other related traits. Two SNPs (rs73885319, rs60910145) and haplotypes (G-A-G; G1; G2) of the apolipoprotein L1 (APOL1) gene were studied in more than one population group, with similar association with prevalent CKD observed. The remaining polymorphisms were investigated in single studies. CONCLUSION: According to this systematic review, there is currently insufficient evidence of the specific polymorphisms that poses African populations at an increased risk of CKD. Large-scale genetic studies are warranted to better understand susceptibility polymorphisms, specific to African populations.

The relationship between immunogenic red blood cell antigens and Human Immunodeficiency Virus infection.

INTRODUCTION: Evidence suggests that red cell antigens may act as receptors for viruses and bacteria and therefore could be associated with HIV infection. Previous studies have been controversial and therefore the aim of this exploratory study was to analyse the expression of immunogenic red cell antigens in HIV-seropositive individuals and to compare the results to negative donors from South Africa. METHODS: The expression of ABO, Rh, Kell and Duffy antigens from 119 HIV-seropositive patients was compared to 317 HIV-seronegative blood donors. Nucleic acid amplification testing and PCR were used to determine the HIV status and the ID-Gel Card Technology was used to determine the blood group antigen profile. RESULTS: There was no significant difference in the expression of A, B, AB, Duffy or Kel antigens between the two groups but significantly lower numbers of HIV+ individuals were O Rh Negative (p = ,0.0001). Analysis of those with a Duffy null phenotype revealed a significantly higher incidence of blood type A RH1-Positive, Dce/R0r and B RH1-Positive, DcEe/R2r within the HIV-seropositive group (p = < 0.05). None of the HIV-seropositive individuals were O RH1-Negative, dce/rr. CONCLUSION: In conclusion these initial findings have demonstrated a decreased incidence of blood type O Rh1-negative in HIV + individuals which suggests that red blood cell antigens may play an important role in susceptibility to HIV infection. The relationship between red cell antigens and HIV infection however remains complex and therefore larger studies are required to confirm these results.

The role of pollutants in type 2 diabetes mellitus (T2DM) and their prospective impact on phytomedicinal treatment strategies.

Type 2 diabetes mellitus (T2DM) is the most common form of diabetes and it is characterized by high blood sugar and abnormal sera lipid levels. Although the specific reasons for the development of these abnormalities are still not well understood, traditionally, genetic and lifestyle behavior have been reported as the leading causes of this disease. In the last three decades, the number of diabetic patients has drastically increased worldwide, with current statistics suggesting the number is to double in the next two decades. To combat this incurable ailment, orthodox medicines, to which economically disadvantaged patients have minimal access to, have been used. Thus, a considerable amalgamation of medicinal plants has recently been proven to possess therapeutic capabilities to manage T2DM, and this has prompted studies primarily focusing on the healing aspect of these plants, and ultimately, their commercialization. Hence, this review aims to highlight the potential threat of pollutants, i.e., polyfluoroalkyl compounds (PFCs), endocrine disrupting chemicals (EDCs) and heavy metals, to medicinal plants, and their prospective impact on the phytomedicinal therapy strategies for T2DM. It is further suggested that auxiliary research be undertaken to better comprehend the factors that influence the uptake of these compounds by these plants. This should include a comprehensive risk assessment of phytomedicinal products destined for the treatment of T2DM. Regulations that control the use of PFC-precursors in certain developing countries are also long overdue.

Recent developments in polyfluoroalkyl compounds research: a focus on human/environmental health impact, suggested substitutes and removal strategies.

Between the late 1940s and early 1950s, humans manufactured polyfluoroalkyl compounds (PFCs) using electrochemical fluorination and telomerisation technologies, whereby hydrogen atoms are substituted by fluorine atoms, thus conferring unnatural and unique physicochemical properties to these compounds. Presently, there are wide ranges of PFCs, and owing to their bioaccumulative properties, they have been detected in various environmental matrices and in human sera. It has thus been suggested that they are hazardous. Hence, this review aims at highlighting the recent development in PFC research, with a particular focus on perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), the most studied and predominantly found PFCs in various environmental matrices, although recent reports have included perfluorobutane sulfonate (PFBS), which was previously regarded as innocuously harmless, when compared to its counterparts, PFOA and PFOS. As such, proper investigations are thus required for a better understanding of short-chain PFC substitutes, which have been suggested as suitable replacements to long-chained PFCs, although these substitutes have also been suggested to pose various health risks comparable to those associated with long-chain PFCs. Similarly, several novel technologies, such as PFC reduction using zero-valent iron, including removal at point of use, adsorption and coagulation, have been proposed. However, regardless of how efficient removers some of these techniques have proven to be, short-chain PFCs remain a challenge to overcome for scientists, in this regard.

APOL1 genetic variants, chronic kidney diseases and hypertension in mixed ancestry South Africans.

BACKGROUND: The frequencies of apolipoprotein L1 (APOL1) variants and their associations with chronic kidney disease (CKD) vary substantially in populations from Africa. Moreover, available studies have used very small sample sizes to provide reliable estimates of the frequencies of these variants in the general population. We determined the frequency of the two APOL1 risk alleles (G1 and G2) and investigated their association with renal traits in a relatively large sample of mixed-ancestry South Africans. APOL1 risk variants (G1: rs60910145 and rs73885319; G2: rs71785313) were genotyped in 859 African mixed ancestry individuals using allele-specific TaqMan technology. Glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. RESULTS: The frequencies of rs73885319, rs60910145 and rs71785313 risk alleles were respectively, 3.6%, 3.4%, and 5.8%, resulting in a 1.01% frequency of the APOL1 two-risk allele (G1:G1 or G1:G2 or G2:G2). The presence of the two-risk allele increased serum creatinine with a corresponding reduction in eGFR (either MDRD or CKD-EPI based). In dominant and log-additive genetic models, significant associations were found between rs71785313 and systolic blood pressure (both p ≤ 0.025), with a significant statistical interaction by diabetes status, p = 0.022, reflecting a negative non-significant effect in nondiabetics and a positive effect in diabetics. CONCLUSIONS: Although the APOL1 variants are not common in the mixed ancestry population of South Africa, the study does provide an indication that APOL1 variants may play a role in conferring an increased risk for renal and cardiovascular risk in this population.

Validation of two prediction models of undiagnosed chronic kidney disease in mixed-ancestry South Africans.

BACKGROUND: Chronic kidney disease (CKD) is a global challenge. Risk models to predict prevalent undiagnosed CKD have been published. However, none was developed or validated in an African population. We validated the Korean and Thai CKD prediction model in mixed-ancestry South Africans. METHODS: Discrimination and calibration were assessed overall and by major subgroups. CKD was defined as 'estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2)' or 'any nephropathy'. eGFR was based on the 4-variable Modification of Diet in Renal Disease (MDRD) formula. RESULTS: In all 902 participants (mean age 55 years) included, 259 (28.7 %) had prevalent undiagnosed CKD. C-statistics were 0.76 (95 % CI: 0.73-0.79) for 'eGFR <60 ml/min/1.73 m(2)' and 0.81 (0.78-0.84) for 'any nephropathy' for the Korean model; corresponding values for the Thai model were 0.80 (0.77-0.83) and 0.77 (0.74-0.81). Discrimination was better in men, older and normal weight individuals. The model underestimated CKD risk by 10 % to 13 % for the Thai and 9 % to 93 % for the Korean model. Intercept adjustment significantly improved the calibration with an expected/observed risk of 'eGFR <60 ml/min/1.73 m(2)' and 'any nephropathy' respectively of 0.98 (0.87-1.10) and 0.97 (0.86-1.09) for the Thai model; but resulted in an underestimation by 24 % with the Korean model. Results were broadly similar for CKD derived from the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. CONCLUSION: Asian prevalent CKD risk models had acceptable performances in mixed-ancestry South Africans. This highlights the potential importance of using existing models for risk CKD screening in developing countries.

Risk predictive modelling for diabetes and cardiovascular disease.

Absolute risk models or clinical prediction models have been incorporated in guidelines, and are increasingly advocated as tools to assist risk stratification and guide prevention and treatments decisions relating to common health conditions such as cardiovascular disease (CVD) and diabetes mellitus. We have reviewed the historical development and principles of prediction research, including their statistical underpinning, as well as implications for routine practice, with a focus on predictive modelling for CVD and diabetes. Predictive modelling for CVD risk, which has developed over the last five decades, has been largely influenced by the Framingham Heart Study investigators, while it is only ∼20 years ago that similar efforts were started in the field of diabetes. Identification of predictive factors is an important preliminary step which provides the knowledge base on potential predictors to be tested for inclusion during the statistical derivation of the final model. The derived models must then be tested both on the development sample (internal validation) and on other populations in different settings (external validation). Updating procedures (e.g. recalibration) should be used to improve the performance of models that fail the tests of external validation. Ultimately, the effect of introducing validated models in routine practice on the process and outcomes of care as well as its cost-effectiveness should be tested in impact studies before wide dissemination of models beyond the research context. Several predictions models have been developed for CVD or diabetes, but very few have been externally validated or tested in impact studies, and their comparative performance has yet to be fully assessed. A shift of focus from developing new CVD or diabetes prediction models to validating the existing ones will improve their adoption in routine practice.

Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1 Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa.

BACKGROUND: The peroxisome proliferator-activated receptor gamma (PPARG), Pro12Ala and the insulin receptor substrate (IRS1), Gly972Arg confer opposite effects on insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the independent and joint effects of PPARG Pro12Ala and IRS1 Gly972Arg on markers of insulin resistance and T2DM in an African population with elevated risk of T2DM. In all 787 (176 men) mixed-ancestry adults from the Bellville-South community in Cape Town were genotyped for PPARG Pro12Ala and IRS1 Gly972Arg by two independent laboratories. Glucose tolerance status and insulin resistance/sensitivity were assessed. RESULTS: Genotype frequencies were 10.4% (PPARG Pro12Ala) and 7.7% (IRS1 Gly972Arg). Alone, none of the polymorphisms predicted prevalent T2DM, but in regression models containing both alleles and their interaction term, PPARG Pro12 conferred a 64% higher risk of T2DM. Furthermore PPARG Pro12 was positively associated in adjusted linear regressions with increased 2-hour post-load insulin in non-diabetic but not in diabetic participants. CONCLUSION: The PPARG Pro12 is associated with insulin resistance and this polymorphism interacts with IRS1 Gly972Arg, to increase the risk of T2DM in the mixed-ancestry population of South Africa. Our findings require replication in a larger study before any generalisation and possible application for risk stratification.

Deterioration, improvement of kidney function over time and determinants in the Cape Town Bellville South cohort.

AIM: The aim of the present study was to assess the trajectories of glomerular filtration rate (GFR) and determinants of change during a 3-year period in free-living mixed-ancestry South Africans. METHODS: In all 320 (78.1% women) adults, aged 56.2 years, from Cape Town were examined in 2008 and 2011. Estimated glomerular filtration rate (eGFR) was based on the Modification of Diet in Renal Disease model; and staging of eGFR used the National Kidney Foundation's classification. RESULTS: Mean eGFR (mL/min per 1.73 m2) was 68.6 at baseline and eGFR stages were: > 90 (9.4%), 60-90 (58.7%), 30-60 (28.1%) and < 30 (0.9%). eGFR increased by 8 mL/min during follow-up, reflecting variable trajectories by baseline eGFR stages, sex, hypertension and glucose tolerance (all P-interaction ≤ 0.012). Movements across eGFR stages during follow-up favoured improvement in 113 participants (35.3%), and worsened in 23 (7.2%). In adjusted multinomial logistic regressions, men had a 72% (43-86%) lower chance of improvement, while each mmHg higher systolic blood pressure conferred a 7% (3-11%) risk of deterioration. Equivalent for each 1% HbA1c was 30% (8-56%). Participants with glucose intolerance had 102% (3-297%) higher chances of improvement than diabetics. CONCLUSION: Variable trajectories of eGFR with time were observed in this cohort, reflecting the effects of modifiable risk factors such as hypertension and dysglycaemia.

The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors.

UNLABELLED: The previously reported link between homocysteine and obesity, both identified as established risk factors for multiple sclerosis (MS), has not previously been studied in relation to the fat mass and obesity-associated (FTO) gene. AIM: To investigate the mechanism underlying homocysteine accumulation in MS patients. A total of 114 patients and 195 population-matched controls were analysed for the FTO rs9939609 polymorphism. Homocysteine levels were measured in a subgroup of 60 patients and 87 controls screened for multiple vascular risk factors. After adjustment for potential confounders, the risk-associated FTO rs9939609 A-allele was associated with raised homocysteine levels (p = 0.003) in patients diagnosed with MS, but not in controls. Homocysteine levels correlated positively with body mass index (BMI) (p = 0.045) and total cholesterol levels (p = 0.048). Both homocysteine (p = 0.011) and BMI (p = 0.017) were significantly reduced with higher intake of folate in the diet. Higher BMI also correlated with increased intake of saturated/trans fat (p < 0.01) and low physical activity (p < 0.006). Daily intake of at least five fruits and vegetables had a favourable lowering effect on the Expanded Disability Status Scale (EDSS) (p = 0.035), while smoking increased MS disability (p < 0.001). This study has shown for the first time that having a diagnosis of MS moderates the effect of the FTO rs9939609 polymorphism on homocysteine levels. This is consistent with the role of FTO in demethylation and epigenetic changes. Identification of FTO rs9939609 reinforces the importance of adequate fruit, vegetable and folate and restriction of saturated/trans fat intake in the diet.

The protective role of resveratrol against high glucose-induced oxidative stress and apoptosis in HepG2 cells.

High glucose concentrations result in oxidative stress, leading to damage of cellular constituents like DNA, proteins, and lipids, ultimately resulting in apoptosis. Resveratrol, a polyphenol phytoalexin, has been studied for its potential therapeutic effects on diabetes. This study investigated the influence of high glucose (HG) on HepG2 cells and assessed resveratrol's effect on high-glucose-induced oxidative stress and apoptosis. HepG2 cells were cultured for 48 and 72 h with high glucose (40 mM), low resveratrol (25 µM), high resveratrol (50 µM), high glucose + low resveratrol, and high glucose + high resveratrol. After exposure, oxidative and apoptosis-related gene expression was evaluated using quantitative polymerase chain reaction (qPCR), and lactate dehydrogenase (LDH) release was measured using the supernatant. In HepG2 cells cultured with high glucose, all antioxidant enzymes (SOD, superoxide dismutase; GPx1, glutathione peroxidase 1; CAT, catalase; Nrf2, nuclear factor erythroid 2-related factor 2; and NQO1, NAD(P)H quinone oxidoreductase 1) were significantly reduced; however, when HepG2 cells were cultured with resveratrol (25 and 50 µM) and high glucose, the expression levels of all antioxidant enzymes were increased. The anti-apoptotic gene (B-cell lymphoma 2; Bcl2) and the DNA repair gene (Oxoguanine glycosylase-1, OGG1) were significantly decreased following high glucose exposure to HepG2 cells. Surprisingly, the expression levels of Bcl2 and OGG1 were notably elevated after resveratrol treatment. Furthermore, high glucose levels increased the LHD release in HepG2 cells, whereas resveratrol treatment reduced the LDH release. Our results demonstrate that resveratrol provides protection against oxidative stress and apoptosis induced by high glucose in HepG2 cells. Hence, resveratrol shows potential as an effective approach to address the impaired antioxidant response resulting from elevated glucose levels commonly observed in diabetes and metabolic disorders.

Resveratrol attenuates high glucose-induced inflammation and improves glucose metabolism in HepG2 cells.

Diabetes mellitus (DM) is characterized by impaired glucose and insulin metabolism, resulting in chronic hyperglycemia. Hyperglycemia-induced inflammation is linked to the onset and progression of diabetes. Resveratrol (RES), a polyphenol phytoalexin, is studied in diabetes therapeutics research. This study evaluates the effect of RES on inflammation and glucose metabolism in HepG2 cells exposed to high glucose. Inflammation and glucose metabolism-related genes were investigated using qPCR. Further, inflammatory genes were analyzed by applying ELISA and Bioplex assays. High glucose significantly increases IKK-α, IKB-α, and NF-kB expression compared to controls. Increased NF-kB expression was followed by increased expression of pro-inflammatory cytokines, such as TNF-α, IL-6, IL-ß, and COX2. RES treatment significantly reduced the expression of NF-kB, IKK-α, and IKB-α, as well as pro-inflammatory cytokines. High glucose levels reduced the expression of TGFß1, while treatment with RES increased the expression of TGFß1. As glucose levels increased, PEPCK expression was reduced, and GCK expression was increased in HepG2 cells treated with RES. Further, HepG2 cells cultured with high glucose showed significant increases in KLF7 and HIF1A but decreased SIRT1. Moreover, RES significantly increased SIRT1 expression and reduced KLF7 and HIF1A expression levels. Our results indicated that RES could attenuate high glucose-induced inflammation and enhance glucose metabolism in HepG2 cells.

Investigating the altered expression of miR-486-5p and miR-novel-chr1_40444 in dysglycemia in a South African population.

AIMS: This study aims to investigate miR-486-5p and miR-novel-chr1_40444 expressions in dysglycemic individuals. Validating RNA-sequencing findings in a larger sample via reverse transcription qPCR (RT-qPCR), we aim to address global diagnostic and screening limitations, using an African cohort as an example. MATERIALS AND METHODS: This cross-sectional study involved 1,271 individuals [normoglycemic (n = 974), prediabetic (n = 206), screen-detected type 2 diabetes (n = 91)] from the ongoing Vascular and Metabolic Health (VMH) study in Cape Town, South Africa. Whole blood miRNA expression was assessed using TaqMan-based RT-qPCR, with data normalized to an endogenous control (miR-16-5p). RESULTS: Significant underexpression was observed in prediabetes vs normoglycemia for miR-486-5p (P = 0.038), whilst both miRNAs demonstrated significant upregulation in screen-detected type 2 diabetes vs normoglycemia (miR-486-5p, P = 0.009; miR-novel-chr1_40444, P < 0.001), and screen-detected type 2 diabetes in comparison with prediabetes (miR-486-5p, P < 0.001; miR-novel-chr1_40444, P < 0.001). Multivariable regression analyses revealed pronounced interrelations between miR-novel-chr1_40444 and screen-detected type 2 diabetes in unadjusted and adjusted models (Model 1: P < 0.001, Model 2: P < 0.001, Model 3: P = 0.030). Moreover, receiver operating characteristic (ROC) curves revealed significantly enhanced diagnostic capabilities for screen-detected type 2 diabetes vs either normoglycemia (AUC = 0.971, P < 0.001), non-diabetes (AUC = 0.959, P < 0.001), or prediabetes (AUC = 0.902, P < 0.001) when combining the miRNAs with 2 h postprandial glucose. CONCLUSIONS: This study demonstrated the enhanced power of incorporating miRNAs with traditional markers in distinguishing screen-detected type 2 diabetes, warranting further investigations on their unique role in the development of type 2 diabetes.

The effect of cigarette smoking on the oral microbiota in a South African population using subgingival plaque samples.

Disturbances in the oral microbiota may be due to several mechanisms and factors, such as smoking. An imbalance in oral bacteria may result in changes to the innate immune system and the development of periodontal disease. This study aimed to investigate the distribution of oral microbiota in smokers and non-smokers in a South African population using subgingival plaque samples. From the 128 recruited participants, 57 were identified as smokers (serum cotinine: >15 ng/ml). Analysis of 16S rRNA gene sequencing demonstrated significant differences between the two groups with a reduced abundance of Actinobacteria in smokers. Fusobacterium and Campylobacter were found in higher abundance, while a lower abundance of Leptotrichia, Actinomyces, Corynebacterium, and Lautropia were observed. This study highlighted significant differences in the oral microbiota of smokers, indicating an abundance of anaerobic gram-negative bacteria. These findings suggest that smoking allows certain oral microorganisms to gain dominance, thereby predisposing individuals to periodontal disease development and progression.

Utility of waist-to-height ratio, waist circumference and body mass index in predicting clustered cardiometabolic risk factors and subclinical vascular phenotypes in children and adolescents: A pooled analysis of individual data from 14 countries.

AIMS: The clinical utility of waist-to-height ratio (WHtR) in predicting cardiometabolic risk factors (CMRFs) and subclinical markers of cardiovascular disease remains controversial. We aimed to compare the utility of WHtR with waist circumference (WC) and body mass index (BMI) in identifying children and adolescents (youths) at risk for cardiometabolic outcomes, including clustered CMRFs, high carotid intima-media thickness (cIMT), and arterial stiffness (assessed as high pulse wave velocity, PWV). METHODS: We analyzed data from 34,224 youths (51.0 % boys, aged 6-18 years) with CMRFs, 5004 (49.5 % boys, aged 6-18 years) with cIMT measurement, and 3100 (56.4 % boys, aged 6-17 years) with PWV measurement from 20 pediatric samples across 14 countries. RESULTS: WHtR, WC, and BMI z-scores had similar performance in discriminating youths with ≥3 CMRFs, with the area under the curve (AUC) (95 % confidence interval, CI)) ranging from 0.77 (0.75-0.78) to 0.78 (0.76-0.80) using the modified National Cholesterol Education Program (NCEP) definition, and from 0.77 (0.74-0.79) to 0.77 (0.74-0.80) using the International Diabetes Federation (IDF) definition. Similarly, all three measures showed similar performance in discriminating youths with subclinical vascular outcomes, with AUC (95 % CI) ranging from 0.67 (0.64-0.71) to 0.70 (0.66-0.73) for high cIMT (≥P95 values) and from 0.60 (0.58-0.66) to 0.62 (0.58-0.66) for high PWV (≥P95 values). CONCLUSIONS: Our findings suggest that WHtR, WC, and BMI are equally effective in identifying at-risk youths across diverse pediatric populations worldwide. Given its simplicity and ease of use, WHtR could be a preferable option for quickly screening youths with increased cardiometabolic risk in clinical settings.