The prognostic impact of insulin resistance surrogates in patients with acute myocardial infarction with and without type 2 diabetes.

BACKGROUND: Cardiovascular disease is the major cause of morbidity and mortality, particularly in type 2 diabetes mellitus (T2DM). Novel markers of insulin resistance and progression of atherosclerosis include the triglycerides and glucose index (TyG index), the triglycerides and body mass index (Tyg-BMI) and the metabolic score for insulin resistance (METS-IR). Establishing independent risk factors for in-hospital death and major adverse cardiac and cerebrovascular events (MACCE) in patients with myocardial infarction (MI) remains critical. The aim of the study was to assess the risk of in-hospital death and MACCE within 12 months after ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation myocardial infarction (NSTEMI) in patients with and without T2DM based on TyG index, Tyg-BMI and METS-IR. METHODS: Retrospective analysis included 1706 patients with STEMI and NSTEMI hospitalized between 2013 and 2021. We analyzed prognostic value of TyG index, Tyg-BMI and METS-IR for in-hospital death and MACCE as its components (death from any cause, MI, stroke, revascularization) within 12 months after STEMI or NSTEMI in patients with and without T2DM. RESULTS: Of 1706 patients, 58 in-hospital deaths were reported (29 patients [4.3%] in the group with T2DM and 29 patients [2.8%] in the group without T2DM; p = 0.1). MACCE occurred in 18.9% of the total study population (25.8% in the group with T2DM and 14.4% in the group without T2DM; p < 0.001). TyG index, Tyg-BMI and METS-IR were significantly higher in the group of patients with T2DM compared to those without T2DM (p < 0.001). Long-term MACCE were more prevalent in patients with T2DM (p < 0.001). The area under the ROC curve (AUC-ROC) for the prediction of in-hospital death and the TyG index was 0.69 (p < 0.001). The ROC curve for predicting in-hospital death based on METS-IR was 0.682 (p < 0.001). The AUC-ROC values for MACCE prediction based on the TyG index and METS-IR were 0.582 (p < 0.001) and 0.57 (p < 0.001), respectively. CONCLUSIONS: TyG index was an independent risk factor for in-hospital death in patients with STEMI or NSTEMI. TyG index, TyG-BMI and METS-IR were not independent risk factors for MACCE at 12 month follow-up. TyG index and METS-IR have low predictive value in predicting MACCE within 12 months after STEMI and NSTEMI.

Effect of different optimization parameters in single isocenter multiple brain metastases radiosurgery.

PURPOSE: Automated treatment planning for multiple brain metastases differs from traditional planning approaches. It is therefore helpful to understand which parameters for optimization are available and how they affect the plan quality. This study aims to provide a reference for designing multi-metastases treatment plans and to define quality endpoints for benchmarking the technique from a scientific perspective. METHODS: In all, 20 patients with a total of 183 lesions were retrospectively planned according to four optimization scenarios. Plan quality was evaluated using common plan quality parameters such as conformity index, gradient index and dose to normal tissue. Therefore, different scenarios with combinations of optimization parameters were evaluated, while taking into account dependence on the number of treated lesions as well as influence of different beams. RESULTS: Different scenarios resulted in minor differences in plan quality. With increasing number of lesions, the number of monitor units increased, so did the dose to healthy tissue and the number of interlesional dose bridging in adjacent metastases. Highly modulated cases resulted in 4-10% higher V10% compared to less complex cases, while monitor units did not increase. Changing the energy to a flattening filter free (FFF) beam resulted in lower local V12Gy (whole brain-PTV) and even though the number of monitor units increased by 13-15%, on average 46% shorter treatment times were achieved. CONCLUSION: Although no clinically relevant differences in parameters where found, we identified some variation in the dose distributions of the different scenarios. Less complex scenarios generated visually more dose overlap; therefore, a more complex scenario may be preferred although differences in the quality metrics appear minor.

TorS - Reframing a rational for type 2 diabetes treatment.

The mammalian target of rapamycin complex 1 syndrome (Tors), paradigm implies an exhaustive cohesive disease entity driven by a hyperactive mTORC1, and which includes obesity, type 2 diabetic hyperglycemia, diabetic dyslipidemia, diabetic cardiomyopathy, diabetic nephropathy, diabetic peripheral neuropathy, hypertension, atherosclerotic cardiovascular disease, non-alcoholic fatty liver disease, some cancers, neurodegeneration, polycystic ovary syndrome, psoriasis and other. The TorS paradigm may account for the efficacy of standard-of-care treatments of type 2 diabetes (T2D) in alleviating the glycaemic and non-glycaemic diseases of TorS in T2D and non-T2D patients. The TorS paradigm may generate novel treatments for TorS diseases.

Biological aging mediates the associations of metabolic score for insulin resistance with all-cause and cardiovascular disease mortality among US adults: A nationwide cohort study.

AIM: To investigate the associations of metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular disease (CVD)-specific mortality and the potential mediating role of biological ageing. METHODS: A cohort of 19 204 participants from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 was recruited for this study. Cox regression models, restricted cubic splines, and Kaplan-Meier survival curves were used to determine the relationships of METS-IR with all-cause and CVD-specific mortality. Mediation analyses were performed to explore the possible intermediary role of biological ageing markers, including phenotypic age (PhenoAge) and biological age (BioAge). RESULTS: During a median follow-up of 9.17 years, we observed 2818 deaths, of which 875 were CVD-specific. Multivariable Cox regression showed that the highest METS-IR level (Q4) was associated with increased all-cause (hazard ratio [HR] 1.38, 95% confidence interval [CI] 1.14-1.67) and CVD mortality (HR 1.52, 95% CI 1.10-2.12) compared with the Q1 level. Restricted cubic splines showed a nonlinear relationship between METS-IR and all-cause mortality. Only METS-IR above the threshold (41.02 µg/L) was positively correlated with all-cause death. METS-IR had a linear positive relationship with CVD mortality. In mediation analyses, we found that PhenoAge mediated 51.32% (p < 0.001) and 41.77% (p < 0.001) of the association between METS-IR and all-cause and CVD-specific mortality, respectively. For BioAge, the mediating proportions of PhenoAge were 21.33% (p < 0.001) and 15.88% (p < 0.001), respectively. CONCLUSIONS: This study highlights the detrimental effects of insulin resistance, as measured by METS-IR, on all-cause and CVD mortality. Moreover, it underscores the role of biological ageing in mediating these associations, emphasizing the need for interventions targeting both insulin resistance and ageing processes to mitigate mortality risks in metabolic disorders.

Association between anti-mullerian hormone and metabolic syndrome: insights from a prospective community-based study.

BACKGROUND: Limited studies have investigated the relationship between Anti-Müllerian hormone (AMH) and metabolic syndrome (MetS), yielding inconclusive results. This study aimed to examine the relationship between AMH levels and MetS and its components in women from a general population. METHODS: This prospective study recruited 769 women. Generalized Estimating Equation (GEE) models analyzed longitudinal trends of MetS components. Cox proportional hazard models evaluated effect of age-specific AMH tertiles on MetS occurrence, adjusting for confounders. RESULTS: The GEE analysis indicated that women in the third tertile exhibited higher mean FPG compared to those in the first tertile of age-specific AMH (3 mg/dL; 95% CI: 0.40, 5.60; P = 0.024); however, this association became non-significant after adjustment. Notably, the second tertile showed a significant decrease in FPG mean changes over time (-0.69 mg/dL; 95% CI: -1.31, -0.07; P Interaction = 0.030). Women in the second and third tertiles of age-specific AMH demonstrated lower mean HDL-C compared to the first tertile (-2.96 mg/dL; 95% CI: -4.67, -1.26; P < 0.001 and -2.63 mg/dL; 95% CI: -4.31, -0.96; P = 0.002, respectively). The association between HDL-C changes and the second tertile remained significant after adjustment (-1.91 mg/dL; 95% CI: -3.68, -0.14; P = 0.034). No significant associations were observed between age-specific AMH tertiles and TG and SBP/DBP. Cox models revealed no significant differences in the hazard ratio of MetS between AMH tertiles after adjusting for confounders. CONCLUSION: Despite minor variations in MetS components, AMH levels did not affect MetS risk in women from a general population.

Associations between urine glyphosate levels and metabolic health risks: insights from a large cross-sectional population-based study.

BACKGROUND: The prevalence of metabolic syndrome (MetS) in American adults increased from 37.6% in the 2011-12 period to 41.8% in 2017-2018. Environmental exposure, particularly to common compounds such as glyphosate, has drawn increasing attention as a potential risk factor. METHODS: We employed three cycles of data (2013-2018) from the National Health and Nutrition Examination Survey (NHANES) in a cross-sectional study to examine potential associations between urine glyphosate measurements and MetS incidence. We first created a MetS score using exploratory factor analysis (EFA) of the International Diabetes Federation (IDF) criteria for MetS, with data drawn from the 2013-2018 NHANES cycles, and validated this score independently on an additional associated metric, the albumin-to-creatinine (ACR) ratio. The score was validated via a machine learning approach in predicting the ACR score via binary classification and then used in multivariable regression to test the association between quartile-categorized glyphosate exposure and the MetS score. RESULTS: In adjusted multivariable regressions, regressions between quartile-categorized glyphosate exposure and MetS score showed a significant inverted U-shaped or saturating dose‒response profile, often with the largest effect for exposures in quartile 3. Exploration of potential effect modification by sex, race, and age category revealed significant differences by race and age, with older people (aged > 65 years) and non-Hispanic African American participants showing larger effect sizes for all exposure quartiles. CONCLUSIONS: We found that urinary glyphosate concentration is significantly associated with a statistical score designed to predict MetS status and that dose-response coefficient is nonlinear, with advanced age and non-Hispanic African American, Mexican American and other Hispanic participants exhibiting greater effect sizes.

Preconceptional maternal hyperandrogenism and metabolic syndrome risk in male offspring: a long-term population-based study.

PURPOSE: There is limited research on the effects of maternal hyperandrogenism (MHA) on cardiometabolic risk factors in male offspring. We aimed to compare the risk of metabolic syndrome (MetS) in sons of women with preconceptional hyperandrogenism (HA) to those of non-HA women in later life. METHODS: Using data obtained from the Tehran Lipid and Glucose Cohort Study, with an average of 20 years follow-up, 1913 sons were divided into two groups based on their MHA status, sons with MHA (n = 523) and sons without MHA (controls n = 1390). The study groups were monitored from the baseline until either the incidence of events, censoring, or the end of the study period, depending on which occurred first. Age-scaled unadjusted and adjusted Cox regression models were utilized to evaluate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MHA and MetS in their sons. RESULTS: There was no significant association between MHA and HR of MetS in sons with MHA compared to controls, even after adjustment (unadjusted HR (95% CI) 0.94 (0.80-1.11), P = 0.5) and (adjusted HR (95% CI) 0.98 (0.81-1.18), P = 0.8). Sons with MHA showed a HR of 1.35 for developing high fasting blood sugar compared to controls (unadjusted HR (95% CI) 1.35 (1.01-1.81), P = 0.04), however, after adjustment this association did not remain significant (adjusted HR (95% CI) 1.25 (0.90-1.74), P = 0.1). CONCLUSION: The results suggest that preconceptional MHA doesn't increase the risk of developing MetS in sons in later life. According to this suggestion, preconceptional MHA may not have long-term metabolic consequences in male offspring.

Investigating a novel surrogate indicator of adipose accumulation in relation to erectile dysfunction.

INTRODUCTION: Although previous studies have linked obesity and erectile dysfunction, the novel surrogate indicators of adipose accumulation are more essential and dependable factors to consider. Therefore, the primary objective of the current investigation was to examine and clarify the association between metabolic score for visceral fat (METS-VF) and erectile dysfunction. METHODS: Firstly, multivariate logistic regression analysis, smoothed curve fitting, and threshold effect analysis were employed to investigate the association between METS-VF and erectile dysfunction. Mediation analysis was also performed to evaluate the mediating role of homocysteine and inflammation. After that, subgroup analysis was carried out to examine the stability of the correlation of METS-VF with erectile dysfunction in various population settings. Furthermore, the area under the receiver operating characteristic (ROC) curve and eXtreme Gradient Boosting (XGBoost) algorithm were utilized to assess the capability of identifying METS-VF in comparison to the other four obesity-related indicators in identifying erectile dysfunction. RESULTS: After adjusting for all confounding factors, METS-VF was strongly and favourablely correlated with erectile dysfunction. With each additional unit rise in METS-VF, the prevalence of erectile dysfunction increased by 141%. A J-shaped relationship between METS-VF and erectile dysfunction was discovered through smoothed curve fitting. Marital status, physical activity, and smoking status can potentially modify this association. This finding of the ROC curve suggests that METS-VF had a powerful identifying capacity for erectile dysfunction (AUC = 0.7351). Homocysteine and inflammation mediated 4.24% and 2.81%, respectively. CONCLUSION: The findings of the current investigation suggest that METS-VF can be considered a dependable identifying indicator of erectile dysfunction.

Metabolic syndrome increases osteoarthritis risk: findings from the UK Biobank prospective cohort study.

OBJECTIVE: The association between Metabolic Syndrome (MetS), its components, and the risk of osteoarthritis (OA) has been a topic of conflicting evidence in different studies. The aim of this present study is to investigate the association between MetS, its components, and the risk of OA using data from the UK Biobank. METHODS: A prospective cohort study was conducted in the UK Biobank to assess the risk of osteoarthritis (OA) related to MetS. MetS was defined according to the criteria set by the International Diabetes Federation (IDF). Additionally, lifestyle factors, medications, and the inflammatory marker C-reactive protein (CRP) were included in the model. Cox proportional hazards regression was used to calculate hazard ratios (HR) and 95% confidence intervals (CI). The cumulative risk of OA was analyzed using Kaplan-Meier curves and log-rank tests. To explore potential nonlinear associations between MetS components and OA risk, a restricted cubic splines (RCS) model was employed. In addition, the polygenic risk score (PRS) of OA was calculated to characterize individual genetic risk. RESULTS: A total of 45,581 cases of OA were identified among 370,311 participants, with a median follow-up time of 12.48 years. The study found that individuals with MetS had a 15% higher risk of developing OA (HR = 1.15, 95%CI:1.12-1.19). Additionally, central obesity was associated with a 58% increased risk of OA (HR = 1.58, 95%CI:1.5-1.66), while hyperglycemia was linked to a 13% higher risk (HR = 1.13, 95%CI:1.1-1.15). Dyslipidemia, specifically in triglycerides (HR = 1.07, 95%CI:1.05-1.09) and high-density lipoprotein (HR = 1.05, 95%CI:1.02-1.07), was also found to be slightly associated with OA risk. When stratified by PRS, those in the high PRS group had a significantly higher risk of OA compared to those with a low PRS, whereas no interaction was found between MetS and PRS on OA risks. Furthermore, the presence of MetS significantly increased the risk of OA by up to 35% in individuals with elevated CRP levels (HR = 1.35, 95% CI:1.3-1.4). CONCLUSION: MetS and its components have been found to be associated with an increased risk of OA, particularly in individuals with elevated levels of CRP. These findings highlight the significance of managing MetS as a preventive and intervention measure for OA.

Insulin resistance is associated with the presence and severity of retinopathy in patients with type 2 diabetes.

BACKGROUND: To assess the relationship between novel insulin resistance (IR) indices and the presence and severity of diabetic retinopathy (DR) in patients with type 2 diabetes. METHODS: This is a cross-sectional study involving 2211 patients. The study outcomes were DR events. The study exposures were IR indices including estimated glucose disposal rate (eGDR), natural logarithm of glucose disposal rate (lnGDR), metabolic insulin resistance score (METS-IR), triglyceride glucose index-body mass index (TyG-BMI), triglyceride glucose index-waist-to-hip ratio (TyG-WHR), and triglyceride/high-density lipoprotein cholesterol(TG/HDL-c ratio). We used binary and multivariate ordered logistic regression models to estimate the association between different IR indices and the presence and severity of DR. Subject work characteristic curves were used to assess the predictive power of different IR indices for DR. RESULTS: DR was present in 25.4% of participants. After adjusting for all covariates, per standard deviation (SD) increases in eGDR (ratio [OR] 0.38 [95% CI 0.32-0.44]), lnGDR (0.34 [0.27-0.42]) were negatively associated with the presence of DR. In contrast, per SD increases in METS-IR (1.97 [1.70-2.28]), TyG-BMI (1.94 [1.68-2.25]), TyG-WHR (2.34 [2.01-2.72]) and TG/HDL-c ratio (1.21 [1.08-1.36]) were positively associated with the presence of DR. eGDR was strongly associated with severity of DR. Of all variables, eGDR had the strongest diagnostic value for DR (AUC = 0.757). CONCLUSIONS: Of the six IR indices, eGDR was significantly associated with the presence and severity of DR in patients with type 2 diabetes. eGDR has a good predictive value for DR. Thus, eGDR maybe a stronger marker of DR.

Off-iso Winston-Lutz test on seven linear accelerators.

PURPOSE: The aim of this study is to find optimal gantry, collimator, and couch angles for performing single isocenter, multiple target stereotactic radiosurgery (SIMT-SRS). Nineteen angle sets were tested across seven linear accelerators for radiation-isocenter coincidence and off-isocenter coincidence. The off-isocenter Winston-Lutz test was performed to evaluate the accuracy of isocenter alignment for each angle set, and optimal angle sets as well as maximum off-isocenter distance to target for each angle set was determined. The influence of simulated patient weight on off-iso Winston-Lutz test accuracy was also inspected. METHOD: The SNC MultiMet-WL phantom and MultiMet-WL QA Software v2.1 were used for the direct measurement and analysis of the off-iso Winston-Lutz test (also referred to as Winston-Lutz-Gao test). A two-step method was developed to ensure precise initial placement of the target. Nineteen beams were delivered at 6X energy and 2 × 2 cm field size to each of six targets on the MultiMet Cube with couch kicks at five cardinal angles (90°, 45°, 0°, 315°, and 270°). To reduce imaging uncertainty, only EPID was used in target alignment and test image acquisition. A total of 200 Ibs (90.7 kg) of weight was also used to mimic patient weight. All tests were performed on both the free table and the weighted table. RESULTS: For two new TrueBeam machines, the maximum offset was within the 1 mm tolerance when the off-iso distance is less than 7 cm. Two older VitalBeam machines exhibited unfavorable gantry, couch, and collimator (GCC) angle sets: Linac No. 3 at (0,90,0), (0,270,0) and Linac No. 4 at (0,45,45) and (0,90,0). The C-Series Linacs failed in the majority of GCC angle sets, with Linac No. 5 exhibiting a maximum offset of 1.53 mm. Four of seven machines show a clear trend that offset increases with off-isocenter distance. Additionally, the IGRT table was less susceptible to the addition of simulated patient weight than the ExactCouch. CONCLUSION: Among the seven linear accelerators addressed, newer model machines such as the Varian TrueBeam were more precise than older models, especially in comparison to the C-Series Linacs. The newer machines are more suitable for delivering SIMT-SRS procedures in all GCC angle sets, and the results indicate that newer TrueBeams are capable of performing SIMT-SRS procedures at all angle sets for targets of off-iso distances up to 7 cm. The trend that offset between the target center and radiation field center increases with off-iso distance, however, does not always hold true across machines. This may be comprised by the EPID's severe off-axis horn effect. Lastly, the IGRT couch was less susceptible to patient weight compared to ExactCouch in the off-isocenter Winston-Lutz test.

Relationships between Circulating Biomarkers and Body Composition Parameters in Patients with Metabolic Syndrome: A Community-Based Study.

Metabolic syndrome (MetS) is a complex disease involving multiple physiological, biochemical, and metabolic abnormalities. The search for reliable biomarkers may help to better elucidate its pathogenesis and develop new preventive and therapeutic strategies. In the present population-based study, we looked for biomarkers of MetS among obesity- and inflammation-related circulating factors and body composition parameters in 1079 individuals (with age range between 18 and 80) belonging to an ethnically homogeneous population. Plasma levels of soluble markers were measured by using ELISA. Body composition parameters were assessed using bioimpedance analysis (BIA). Statistical analysis, including mixed-effects regression, with MetS as a dependent variable, revealed that the most significant independent variables were mainly adipose tissue-related phenotypes, including fat mass/weight (FM/WT) [OR (95% CI)], 2.77 (2.01-3.81); leptin/adiponectin ratio (L/A ratio), 1.50 (1.23-1.83); growth and differentiation factor 15 (GDF-15) levels, 1.32 (1.08-1.62); inflammatory markers, specifically monocyte to high-density lipoprotein cholesterol ratio (MHR), 2.53 (2.00-3.15), and a few others. Additive Bayesian network modeling suggests that age, sex, MHR, and FM/WT are directly associated with MetS and probably affect its manifestation. Additionally, MetS may be causing the GDF-15 and L/A ratio. Our novel findings suggest the existence of complex, age-related, and possibly hierarchical relationships between MetS and factors associated with obesity.

Biomolecular Actions by Intestinal Endotoxemia in Metabolic Syndrome.

Metabolic syndrome (MetS) is a combination of metabolic disorders that concurrently act as factors promoting systemic pathologies such as atherosclerosis or diabetes mellitus. It is now believed to encompass six main interacting conditions: visceral fat, imbalance of lipids (dyslipidemia), hypertension, insulin resistance (with or without impairing both glucose tolerance and fasting blood sugar), and inflammation. In the last 10 years, there has been a progressive interest through scientific research investigations conducted in the field of metabolomics, confirming a trend to evaluate the role of the metabolome, particularly the intestinal one. The intestinal microbiota (IM) is crucial due to the diversity of microorganisms and their abundance. Consequently, IM dysbiosis and its derivate toxic metabolites have been correlated with MetS. By intervening in these two factors (dysbiosis and consequently the metabolome), we can potentially prevent or slow down the clinical effects of the MetS process. This, in turn, may mitigate dysregulations of intestinal microbiota axes, such as the lung axis, thereby potentially alleviating the negative impact on respiratory pathology, such as the chronic obstructive pulmonary disease. However, the biomolecular mechanisms through which the IM influences the host's metabolism via a dysbiosis metabolome in both normal and pathological conditions are still unclear. In this study, we seek to provide a description of the knowledge to date of the IM and its metabolome and the factors that influence it. Furthermore, we analyze the interactions between the functions of the IM and the pathophysiology of major metabolic diseases via local and systemic metabolome's relate endotoxemia.

Sperm induce macrophage extracellular trap formation via phagocytosis-dependent mechanism.

Infertility is a public health concern worldwide. Asthenozoospermia is a common cause of male infertility and is characterized by decreased motility. Sperm motility ensures that sperm migrate to complete fertilization. Macrophages are an essential component of innate immunity in the female reproductive tract. Macrophage extracellular traps are induced by various microorganisms to capture and mediate the clearance of microorganisms. The relationship between sperm and macrophage extracellular traps is unclear. The human monocyte leukemia (THP-1) cells differentiated by phorbol myristate acetate (PMA) are widely used as surrogate of human macrophages. This study investigated sperm-induced macrophage extracellular trap formation and clarified some of the mechanisms affecting macrophage extracellular trap production. Sperm-induced macrophage extracellular traps were visualized and components of macrophage extracellular traps were identified by immunofluorescence analyses and scanning electron microscopy. By inhibiting macrophage extracellular trap production and macrophage phagocytosis, the relationship between macrophage phagocytosis and macrophage extracellular trap production was analyzed. Sperm could trigger PMA-differentiated THP-1 macrophages to produce extracellular traps. Sperm-triggered macrophage extracellular traps are dependent on phagocytosis and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. Sperm from asthenozoospermia donors are more likely to be phagocytosed by macrophages than sperm from healthy donors, which induce more macrophage extracellular trap release. These data confirm the phenomenon and partial mechanism of sperm-induced macrophage extracellular trap formation in vitro. These may partly provide evidence to explain the mechanisms of clearing abnormally morphological or hypomotile sperm in the female reproductive tract and the rationale for the decreased probability of successful fertilization in asthenozoospermia.

Non-overweight depressed patients who respond to antidepressant treatment have a higher risk of later metabolic syndrome: findings from the METADAP cohort.

BACKGROUND: Major depressive disorder (MDD) is a complex disorder with a significant public health burden. Depression remission is often associated with weight gain, a major risk factor for metabolic syndrome (MetS). The primary objective of our study was to assess prospectively the impact of response to antidepressant treatment on developing MetS in a sample of MDD patients with a current major depressive episode (MDE) and who are newly initiating their treatment. METHODS: In the 6-month prospective METADAP cohort, non-overweight patients, body mass index <25 kg/m2, with MDD and a current MDE were assessed for treatment response after 3 months of treatment, and incidence of MetS after 3 and 6 months of treatment. Outcome variables were MetS, number of MetS criteria, and each MetS criterion (high waist circumference, high blood pressure, high triglyceridemia, low high-density lipoprotein-cholesterolemia, and high fasting plasma glucose). RESULTS: In total, 98/169 patients (58%) responded to treatment after 3 months. A total of 2.7% (1/38) developed MetS out of which 12.7% (10/79) (p value < 0.001) had responded to treatment after 3 months. The fixed-effect regression models showed that those who responded to treatment after 3 months of follow-up had an 8.6 times higher odds of developing MetS (odds ratio = 8.58, 95% confidence interval 3.89-18.93, p value < 0.001). CONCLUSION: Compared to non-responders, non-overweight patients who responded to treatment after 3 months of antidepressant treatment had a significantly higher risk of developing MetS during the 6 months of treatment. Psychiatrists and nurses should closely monitor the metabolic profile of their patients, especially those who respond to treatment.

Impact of sleep and physical activity habits on real-life glycaemic variability in patients with type 2 diabetes.

The aim of this study was to better characterise whether sleep habits, eating schedule and physical activity in real-life are associated with glycaemic control in patients with type 2 diabetes. A total of 28 patients (aged 60 years [58; 66], 54% female) with type 2 diabetes treated with basal-bolus insulin therapy administered by insulin pumps were analysed. Glycaemic data measured by Flash Glucose Monitor System, physical activity and sleep data measured by accelerometer, and meal schedules were simultaneously collated with insulin pump administration data, for 7 days in real-life. Their respective impact on the time spent in target, in hypoglycaemia, in hyperglycaemia and on glycaemic variability was evaluated. Multiple regressions showed that the total daily dose of meal boluses of insulin was inversely associated with the coefficient of variation (CV; coefficient ß = -0.073; 95% confidence interval: -0.130, -0.015; p = 0.016), as well as sleep duration. The higher the sleep duration, the lower the glycaemic variability (coefficient ß = -0.012; 95% confidence interval: -0.023, -0.002; p = 0.027). The mean 7 days physical activity of the subjects was very low and was not associated with glycaemic control on the 7 days mean values. However, days with at least 1 hr spent in physical activity higher than 1.5 METs were associated with less glycaemic variability that same day. This real-life observation highlights the importance of sufficient sleep duration and regular physical activity to lessen the glycaemic variability of patients with type 2 diabetes.

Moderate-intensity stepping in older adults: insights from treadmill walking and daily living.

BACKGROUND: A step cadence of 100 steps/minute is widely used to define moderate-intensity walking. However, the generalizability of this threshold to different populations needs further research. We investigate moderate-intensity step cadence values during treadmill walking and daily living in older adults. METHODS: Older adults (≥ 60 years) were recruited from urban community venues. Data collection included 7 days of physical activity measured by an activPAL3™ thigh worn device, followed by a laboratory visit involving a 60-min assessment of resting metabolic rate, then a treadmill assessment with expired gas measured using a breath-by-breath analyser and steps measured by an activPAL3™. Treadmill stages were undertaken in a random order and lasted 5 min each at speeds of 1, 2, 3, 4 and 5 km/h. Metabolic equivalent values were determined for each stage as standardised values (METSstandard) and as multiples of resting metabolic rate (METSrelative). A value of 3 METSstandard defined moderate-intensity stepping. Segmented generalised estimating equations modelled the association between step cadence and MET values. RESULTS: The study included 53 participants (median age = 75, years, BMI = 28.0 kg/m2, 45.3% women). At 2 km/h, the median METSstandard and METSrelative values were above 3 with a median cadence of 81.00 (IQR 72.00, 88.67) steps/minute. The predicted cadence at 3 METSstandard was 70.3 (95% CI 61.4, 75.8) steps/minute. During free-living, participants undertook median (IQR) of 6988 (5933, 9211) steps/day, of which 2554 (1297, 4456) steps/day were undertaken in continuous stepping bouts lasting ≥ 1 min. For bouted daily steps, 96.4% (90.7%, 98.9%) were undertaken at ≥ 70 steps/minute. CONCLUSION: A threshold as low as 70 steps/minute may be reflective of moderate-intensity stepping in older adults, with the vast majority of all bouted free-living stepping occurring above this threshold.

Metabolic syndrome among people living with HIV on antiretroviral therapy in Mwanza, Tanzania.

BACKGROUND: HIV and antiretroviral drugs, particularly protease inhibitors and nucleoside reverse transcriptase inhibitors, may increase the risk of Metabolic Syndrome (MetS) among people living with HIV (PLHIV). However, following the introduction of better drugs like dolutegravir, data on the burden of MetS are limited. This study aimed to assess the prevalence of MetS and associated factors among PLHIV on antiretroviral therapy (ART) in Tanzania. METHODS: This was a cross-sectional study among PLHIV aged ≥ 18 years on antiretroviral therapy for ≥ 1 year at Bugando Medical Centre in Mwanza conducted in 2020. Demographic and healthy-lifestyle-related non-communicable disease risk factors data were collected. Additionally, data on lipid profile, blood glucose, blood pressure, and waist circumference were collected for analysis of MetS according to the International Diabetes Federation criteria. Factors associated with MetS were assessed using logistic regression. A P ≤ 0.05 was considered statistically significant. RESULTS: Data for 223 participants were analyzed. The mean (SD) age was 44 (± 12) years and 79.8% (178) were females. A majority 78% (174) were on a tenofovir, lamivudine,and dolutegravir regimen. About 12.1% (27) were either current or past smokers, 45.3% (101) were past alcohol drinkers, 22.9% (51) were current drinkers, 12.1% (27) reported taking ≥ 5 servings of vegetables and fruits per day and 5.8% (13) were physically inactive. The prevalence of MetS was 22.9%. The only factors that were associated with Mets were fat mass index and adequate intake of vegetables and fruits, (adjusted odds ratio (aOR) 2.9, 95% CI 1.0, 7.9, P = 0.04) and (aOR1.2, 95% CI 1.0, 1.3, P = 0.02), respectively). CONCLUSION: The prevalence of MetS remains high among PLHIV. Adiposity and adequate fruit and vegetable intake increased the risk. The introduction of new ART regimens shows no effect on MetS prevalence. Research is needed to understand how lifestyle changes could reduce MetS in PLHIV.

Black carbon nanoparticles activate the crosstalk mechanism between necroptosis and macrophage extracellular traps to change macrophages fate.

PM2.5 still poses a threat to public health even at very low levels. Black carbon (BC) is a key component of PM2.5. Macrophage extracellular traps (METs) are a means by which macrophages capture and destroy invading pathogens. Necroptosis is an inflammatory programmed cell death. However, there is no research on the crosstalk mechanism between necroptosis and METs after BC exposure. In our study, fluorescence labeling, fluorescent probes, qPCR, and immunofluorescence were applied. Our research found that under normal physiological conditions, when macrophages receive external stimuli (in our experiment, phorbol 12-myristate 13-acetate (PMA)), they will form METs, thus exhibiting innate immune function. However, exposure to BC can cause necroptosis in macrophages accompanied by increased levels of ROS and cytosolic calcium ions as well as altered expression of inflammatory factors and chemokines that prevent the formation of METs, and weakening innate immune function. Notably, inhibition of necroptosis restored the formation of METs, indicating that necroptosis inhibits the formation of METs. Our experiment will enrich the understanding of the mechanism of macrophage injury caused by BC exposure, provide a new direction for studying harmful atmospheric particle toxicity, and propose new therapeutic insights for diseases caused by atmospheric particulate matter. This study is the first to explore the crosstalk mechanism between necroptosis and METs after BC exposure.

Cross-sectional associations of persistent organic pollutants measured in adipose tissue and metabolic syndrome in clinically diagnosed middle-aged adults.

INTRODUCTION: Although often overlooked in clinical settings, accumulation of persistent organic pollutants (POPs) in visceral adipose tissue (VAT) is thought to be a relevant risk factor for metabolic syndrome (MetS). METHODS: One hundred and seventeen patients undergoing non-oncological surgery were randomly recruited and classified as MetS + if presented 3 out of the 5 MetS components: waist circumference (WC), systolic and diastolic blood pressure (SBP and DBP, respectively), serum glucose, insulin, triglycerides (TG) and high-density lipoprotein (HDL) cholesterol levels, according International Diabetes Federation (IDF) criteria. Seventeen organochlorine pesticides (OCPs) and polychlorinated biphenyls (PCBs) were measured in adipose tissue samples. Linear, logistic and weighted quantile sum (WQS) regression models, adjusted for age and sex, were performed. RESULTS: One third of the participants were males (36.8%) with a median age of 44 years, showing clinical evidences of MetS (35.0%). Adjusted linear regression models showed that WC correlated positively with all OCP concentrations. Higher fasting serum glucose levels were related to higher HCB and γ-HCH concentrations. The remaining OCPs and PCBs were not associated with this MetS component. HCB was inversely associated with HDL cholesterol levels, while PCB-180 was positively associated. HCB and γ-HCH concentrations were also positively correlated with DBP and SBP levels. PCB-138 was also positively associated with SBP. Adjusted logistic models revealed that exposure to HCB and γ-HCH were associated with increased odds of MetS [ORs (95%CI) 1.53 (1.22-1.92) and 1.39 (1.10-1.76) respectively; p < 0.01]. No associations were observed for the remaining POPs. WQS models showed a positive and significant mixture effect of POPs on the odds of MetS (exp [beta] = 2.34; p < 0.001), with γ-HCH (52.9%), o,p'-DDT (26.9%) and HCB (19.7%) driving the association. CONCLUSIONS: Our findings support that POPs accumulated in VAT, specifically HCB and (gamma)-HCH, are associated with both isolated components and clinically diagnosed SMT.