Risk Factor For Metabolic Diseases Research Articles

Moderate chronic sleep perturbation impairs glucose and lipid homeostasis in rats.

Sleep deprivation is a potential risk factor for metabolic diseases, including obesity and type 2 diabetes. We evaluated the impacts of moderate chronic sleep deprivation on glucose and lipid homeostasis in adult rats. Wistar rats (both sexes) were sleep-perturbed daily for two hours at the early (06:00-08:00) and the late light cycle (16:00-18:00) five days a week (except weekends) for four weeks. Sleep perturbation (SP) resulted in reduced body weight gain in both sexes, associated with altered food intake and reduced adiposity. SP did not alter the short- or long-term memories or cause anxiogenic behavior. No major changes were observed in the plasma insulin, leptin, triacylglycerol, non-esterified fatty acids and blood glucose upon SP. After SP, females exhibited a transitory glucose intolerance, while males became glucose intolerant at the end of the experimental period. Male rats also developed higher insulin sensitivity at the end of the SP protocol. Morphometric analyses revealed no changes in hepatic glycogen deposition, pancreatic islet mass, islet-cell distribution, or adrenal cortex thickness in SP rats from both sexes, except for lower adipocyte size compared with controls. We did not find homogeneous changes in the relative expression of circadian and metabolic genes in muscle or hepatic tissues from the SP rats. Moderate chronic SP reduces visceral adiposity and causes glucose intolerance with a more pronounced impact on male rats, reinforcing the metabolic risks of exposure to sleep disturbances.

Low MBOAT7 expression, a genetic risk for MASH, promotes a pro-fibrotic pathway involving hepatocyte TAZ upregulation.

The common genetic variant rs641738 C>T is a risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH), including liver fibrosis, and is associated with decreased expression of the phospholipid-remodeling enzyme MBOAT7 (LPIAT1). However, whether restoring MBOAT7 expression in established MASLD dampens the progression to liver fibrosis and, importantly, the mechanism through which decreased MBOAT7 expression exacerbates MASH fibrosis remain unclear. We first showed that hepatocyte MBOAT7 restoration in mice with diet-induced steatohepatitis slows the progression to liver fibrosis. Conversely, when hepatocyte-MBOAT7 was silenced in mice with established hepatosteatosis, liver fibrosis but not hepatosteatosis was exacerbated. Mechanistic studies revealed that hepatocyte-MBOAT7 restoration in MASH mice lowered hepatocyte-TAZ (WWTR1), which is known to promote MASH fibrosis. Conversely, hepatocyte-MBOAT7 silencing enhanced TAZ upregulation in MASH. Finally, we discovered that changes in hepatocyte phospholipids due to MBOAT7 loss-of-function promote a cholesterol trafficking pathway that upregulates TAZ and the TAZ-induced profibrotic factor Indian hedgehog (IHH). As evidence for relevance in humans, we found that the livers of individuals with MASH carrying the rs641738-T allele had higher hepatocyte nuclear TAZ, indicating higher TAZ activity, and increased IHH mRNA. This study provides evidence for a novel mechanism linking MBOAT7-LoF to MASH fibrosis; adds new insight into an established genetic locus for MASH; and, given the druggability of hepatocyte TAZ for MASH fibrosis, suggests a personalized medicine approach for subjects at increased risk for MASH fibrosis due to inheritance of variants that lower MBOAT7.

Analysis of clinical risk factors for metabolic bone disease of prematurity

ObjectiveTo analyze clinical data related to preterm infants and identify risk factors for metabolic bone disease of prematurity (MBDP).MethodsThis study involved 856 newborns with a gestational age of less than 37 weeks or a weight of less than 1,500g at the Second Hospital of Jilin University. Multifactorial analysis was performed using logistic regression models to explore the risk factors for MBDP. Linear regression was used to investigate the factors affecting the time of alkaline phosphatase (ALP) exceedance and the peak value of ALP in the MBDP group.ResultsIn the MBDP group, ALP excesses occurred in preterm infants at an average of 39.33 days after birth, and the mean value of peak ALP was 691.41 IU/L. Parenteral nutrition and the application of assisted ventilation were independent risk factors for MBDP, with ORs of 1.02 and 1.03 respectively. Gestational age was found to be a protective factor for earlier time of onset of ALP exceedance (β = 2.24,) and the increase in the peak value of ALP (β = −16.30).ConclusionParenteral nutrition and the application of assisted ventilation are independent risk factors for MBDP. Gestational age is a major factor influencing the time of onset of ALP exceedance and the peak value of ALP in infants with MBDP.

Risk factors and lipid metabolism characteristics of early-onset male androgenetic alopecia: A pilot study.

Male androgenetic alopecia (MAA) is a multifactorial disease, with patients presenting at a younger age, which is a risk factor for many metabolic diseases. To explore the risk factors associated with early-onset of MAA and its metabolic characteristics. Forty patients with MAA and 45 healthy controls were collected. The serum levels of fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total testosterone (TT), uric acid (UA), and 25-hydroxyvitamin D (25(OH)D) were measured. Meanwhile, lipid metabolites were detected by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). 37.50% MAA patients had metabolic syndrome, compared to 17.78% in control group (p < 0.05). The levels of HDL-C, UA, and 25(OH)D were decreased in patients with MAA compared to healthy controls (p < 0.05). However, there was no significant difference in the level of TT between the two groups. Additionally, there were no significant differences in the levels of HDL-C, UA, 25(OH)D, and TT among different grades of hair loss (p > 0.05). The lipid profile of early-onset MAA differed significantly from healthy controls. In early-onset MAA, the levels of ceramide (Cer) and sphingomyelin (SM) were significantly lower. Cer(d38:5) and TG(15:0/18:1/18:1) may be the biomarkers. Low HDL-C, UA, and 25(OH)D may be the independent risk factors for early-onset MAA. Abnormal lipid metabolism was observed in early-onset MAA, wherein Cer and SM may serve as protective factors.

Coronary artery disease as a risk factor for metabolic dysfunction-associated steatotic liver disease and liver fibrosis

Introduction and ObjectivesPatients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at an increased cardiovascular risk. On the contrary, non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with coronary heart disease (CHD). However, it is not known whether patients with significant CHD show a higher frequency of liver fibrosis. This study aimed to determine the frequency of MASLD and liver fibrosis in patients with CHD and to assess whether coronary stenosis is significantly associated with MASLD and fibrosis. Patients and MethodsThis observational and analytical study included adult patients without any known liver disease who underwent coronary angiography for suspected coronary artery disease (Jul 2021–Jul 2022). The presence of significant CHD (> 50% stenosis of at least one coronary artery) was determined. Liver elastography (FibroScan®) was performed up to 6 months after the coronary angiographic study to determine liver fibrosis, a measurement of liver stiffness (> 6.5 Kpa). Fisher's test, Mann–Whitney U test, and logistic regression models were used (p<0.05). ResultsThe study included 113 patients (76% men, average age: 63 years [standard deviation: 9.9]), of which 72% presented with significant CHD. The prevalence rate of MASLD was 52%. Liver fibrosis was present in 12% of the patients and all patients in the significant CHD group (p=0.007). An increase in the number of vessels with significant CHD increased the probability of liver fibrosis (odds ratio, 1.79; 95% confidence interval, 1.06–3.04; p=0.029). ConclusionsMASLD is highly prevalent in patients with significant CHD but without known liver damage. These data suggest that MASLD and liver fibrosis should be investigated in patients with CHD. The presence of confounding variables, especially the presence of type 2 diabetes mellitus, should be evaluated in further studies.

A Cross-Sectional Study of Glomerular Hyperfiltration in Polycystic Ovary Syndrome.

Glomerular hyperfiltration (GH) has been reported to be higher in women with polycystic ovary syndrome (PCOS) and is an independent risk factor for renal function deterioration, metabolic, and cardiovascular disease. The aim of this study was to determine GH in type A PCOS subjects and to identify whether inflammatory markers, markers of CKD, renal tubule injury markers, and complement system proteins were associated. In addition, a secondary cohort study was performed to determine if the eGFR had altered over time. In this comparative cross-sectional analysis, demographic, metabolic, and proteomic data from Caucasian women aged 18-40 years from a PCOS Biobank (137 with PCOS, 97 controls) was analyzed. Slow Off-rate Modified Aptamer (SOMA)-scan plasma protein measurement was undertaken for inflammatory proteins, serum markers of chronic kidney disease (CKD), tubular renal injury markers, and complement system proteins. A total of 44.5% of the PCOS cohort had GH (eGFR ≥ 126 mL/min/1.73 m2 (n = 55)), and 12% (n = 17) eGFR ≥ 142 mL/min/1.73 m2 (super-GH(SGH)). PCOS-GH women were younger and had lower creatinine and urea versus PCOS-nonGH. C-reactive protein (CRP), white cell count (WCC), and systolic blood pressure (SBP) were higher in PCOS versus controls, but CRP correlated only with PCOS-SGH alone. Complement protein changes were seen between controls and PCOS-nonGH, and decay-accelerator factor (DAF) was decreased between PCOS-nonGH and PCOS-GSGH (p < 0.05). CRP correlated with eGFR in the PCOS-SGH group, but not with other inflammatory or complement parameters. Cystatin-c (a marker of CKD) was reduced between PCOS-nonGH and PCOS-GSGH (p < 0.05). No differences in tubular renal injury markers were found. A secondary cohort notes review of the biobank subjects 8.2-9.6 years later showed a reduction in eGFR: controls -6.4 ± 12.6 mL/min/1.73 m2 (-5.3 ± 11.5%; decrease 0.65%/year); PCOS-nonGH -11.3 ± 13.7 mL/min/1.73 m2 (-9.7 ± 12.2%; p < 0.05, decrease 1%/year); PCOS-GH (eGFR 126-140 mL/min/17.3 m2) -27.1 ± 12.8 mL/min/1.73 m2 (-19.1 ± 8.7%; p < 0.0001, decrease 2%/year); PCOS-SGH (eGFR ≥ 142 mL/min/17.3 m2) -33.7 ± 8.9 mL/min/17.3 m2 (-22.8 ± 6.0%; p < 0.0001, decrease 3.5%/year); PCOS-nonGH eGFR versus PCOS-GH and PCOS-SGH, p < 0.001; no difference PCOS-GH versus PCOS-SGH. GH was associated with PCOS and did not appear mediated through tubular renal injury; however, cystatin-c and DAF were decreased, and CRP correlated positively with PCOS-SGH, suggesting inflammation may be involved at higher GH. There were progressive eGFR decrements for PCOS-nonGH, PCOS-GH, and PCOS-SGH in the follow-up period which, in the presence of additional factors affecting renal function, may be clinically important in the development of CKD in PCOS.

Roles of Hospital Type and Community Setting in Rate of Screening for Metabolic Disorders Among Psychiatric Patients.

Globally, rates of metabolic disorders continue to climb, leading to significant disease morbidity and mortality. Individuals with mental illness are particularly prone to obesity, and some medications, such as antipsychotics, may increase the risk for metabolic disorders. The American Psychiatric Association and the American Diabetes Association recommend that patients taking antipsychotic medications receive regular screening for metabolic disorders. This study examined hospital and community factors associated with screening these patients for such disorders. The authors combined Centers for Medicare and Medicaid Services (CMS) hospital-level data on screening for metabolic disorders among patients with an antipsychotic prescription with community data, including urbanization classification, social vulnerability, and metabolic disease presence and risk factors. Data were merged at the county level and evaluated with a nonparametric multivariate regression model. The CMS data set included 1,497 U.S. hospitals with data on screening for metabolic disorders among patients with an antipsychotic prescription. Screening rates varied by type of facility; acute care and critical access hospitals outperformed freestanding psychiatric facilities (p<0.001). No other variables examined in the multivariate model were associated with screening for metabolic disorders. Despite common resource limitations, screening for metabolic disorders may be driven more by logistics and less by time, finances, or a community's primary care network. Identifying the specific logistical challenges of freestanding psychiatric facilities could aid in the development of targeted interventions to improve the rates of screening for and treatment of not only metabolic disorders but also other common comorbid conditions.

Parental obesity predisposes offspring to kidney dysfunction and increased susceptibility to ischemia-reperfusion injury in a sex-dependent manner.

Although obesity is recognized as a risk factor for cardiorenal and metabolic diseases, the impact of parental obesity on the susceptibility of their offspring to renal injury at adulthood is unknown. We examined the impact of parental obesity on offspring kidney function, morphology, and markers of kidney damage after acute kidney injury (AKI). Offspring from normal (N) diet-fed C57BL/6J parents were fed either N (NN) or a high-fat (H) diet (NH) from weaning until adulthood. Offspring from obese H diet-fed parents were fed N (HN) or H diet (HH) after weaning. All offspring groups were submitted to bilateral AKI by clamping the left and right renal pedicles for 30 min. Compared with male NH and NN offspring from lean parents, male HH and HN offspring from obese parents exhibited higher kidney injury markers such as urinary, renal osteopontin, plasma creatinine, urinary albumin excretion, and neutrophil gelatinase-associated lipocalin (NGAL) levels, and worse histological injury score at 22 wk of age. Only albumin excretion and NGAL were elevated in female HH offspring from obese parents compared with lean and obese offspring from lean parents. We also found an increased mortality rate and worse kidney injury scores after AKI in male offspring from obese parents, regardless of the diet consumed after weaning. Female offspring were protected from major kidney injury after AKI. These results indicate that parental obesity leads to increased kidney injury in their offspring after ischemia-reperfusion in a sex-dependent manner, even when their offspring remain lean.NEW & NOTEWORTHY Offspring from obese parents are more susceptible to kidney injury and worse outcomes following an acute ischemia-reperfusion insult. Male, but not female, offspring from obese parents exhibit increased blood pressure early in life. Female offspring are partially protected against major kidney injury induced by ischemia-reperfusion.

Food insecurity is a risk factor for metabolic dysfunction-associated steatotic liver disease in Latinx children.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease among US children. Studies have associated food insecurity with MASLD in adults, but there are few studies of pediatric MASLD, particularly in high-risk populations. We assessed the impact of household food insecurity at 4 years of age on MASLD in Latinx children. Using a prospective cohort design, Latina mothers were recruited during pregnancy and followed with their children until early to mid-childhood. Our primary exposure was household food insecurity at 4 years of age measured using the validated US Household Food Security Food Module. Our primary outcome, MASLD, was defined as alanine transaminase (ALT) ≥95th% for age/gender plus body mass index (BMI) ≥85% at time of ALT measurement (assessed between ages 5-12). We used multivariable logistic regression models to test for independent associations between household food insecurity and pediatric MASLD. Among 136 children, 28.7% reported household food insecurity at 4 years of age and 27.2% had MASLD in early to middle childhood. Approximately 49% of children with MASLD and 21% of children without MASLD were food insecure (p < 0.01). Exposure to household food insecurity at age 4 was independently associated with a 3.7-fold higher odds of MASLD later in childhood (95% CI: 1.5-9.0, p < 0.01). Exposure to household food insecurity at 4 years of age was associated with increased risk for MASLD later in childhood. Further studies are needed to explore mechanism(s) and impact of reducing food insecurity on risk for MASLD.

Gender Differences in the Predictive Value of Obesity Indices for Insulin Resistance in Adult Mexican Individuals.

Obesity-linked insulin resistance (IR) is an important risk factor for metabolic diseases, and anthropometric indices are commonly used for risk assessment. The study aimed to assess possible differences between women and men in the predictive value and association of nine obesity indices with IR, as assessed by HOMA-IR, in a nondiabetic adult population. The cross-sectional study included individuals recruited from a hospital in Mexico City. Indices evaluated were waist circumference (WC), hip circumference (HC), body mass index (BMI), waist-to-hip ratio, waist-to-height ratio, visceral adiposity index, body adiposity index (BAI), relative fat mass (RFM), and conicity index (CI). Fasting plasma glucose and insulin were measured to calculate HOMA-IR. Correlation analysis was performed between obesity indices and HOMA-IR. Receiver operating characteristics curve analyses were performed to determine predictive accuracy and cut-off values of obesity indices for IR. A binary logistic regression (BLR) analysis with OR calculation was performed to determine the strength of association with HOMA-IR. We included 378 individuals (59% females, mean age 46.38 ±12.25 years). The highest Pearson coefficient value was observed for BMI among women, while among men, the highest values were found for BMI and BAI. WC among women, and BAI and RFM among men showed the highest sensitivity, while the highest specificity was observed for WHR among women and WC among men with respect to insulin prediction. In the adjusted BLR model, BMI, WC, and WHR among women and WC and RFM and BAI among men were independently associated with IR, showing the highest odds ratio (OR). In Mexican adults, WC, WHR, RFM and BAI could be complementary tools for BMI in screening for IR.

Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study

Adverse pregnancy outcomes as a risk factor for new-onset metabolic dysfunction-associated steatotic liver disease in postpartum women: A nationwide study

Triglyceride-glucose index demonstrates reasonable performance as a screening tool but exhibits limited diagnostic utility for insulin resistance: Data from the ELSA-Brasil cohort

Insulin resistance (IR) is a key risk factor for chronic metabolic diseases, but its laboratory diagnosis is still costly; thus, the triglyceride-glucose (TyG) index has been proposed as a surrogate method. Our aim was to provide a detailed analysis of cutoffs and test the hypothesis that the TyG index would present reasonable performance parameters for IR screening. This is a cross-sectional study with baseline data from 12,367 eligible participants of both sexes (aged 35-74 years) from the Brazilian Longitudinal Study of Adult Health. TyG correlation and agreement with the Homeostasis Model Assessment for Insulin Resistance were analyzed. Positive and negative predictive values (PV+, PV-) and likelihood ratio (LR+, LR-) were calculated. A moderate positive correlation between TyG and Homeostasis Model Assessment for Insulin Resistance was observed (Pearson r = 0.419). The area under the receiver operating characteristic curve of TyG for IR diagnosis was 0.742 and the optimal cutoff was 4.665, reaching a kappa agreement value of 0.354. For this cutoff, a PV+ of 59.3% and PV- of 76.0%, as well as an LR+ of 2.07 and LR- of 0.45 were obtained. Alternatively, because high sensitivity is desired for screening tests, selecting a lower cutoff, such as 4.505, increases the PV- to 82.1%, despite decreasing the PV+ to 50.8%. We conclude that TyG has important performance limitations for detecting IR, but that it may still be reasonably useful to help screening for IR in adults because it can be calculated from low-cost routine blood tests.

Comprehensive genetic study of the insulin resistance marker TG:HDL-C in the UK Biobank.

Insulin resistance (IR) is a well-established risk factor for metabolic disease. The ratio of triglycerides to high-density lipoprotein cholesterol (TG:HDL-C) is a surrogate marker of IR. We conducted a genome-wide association study of the TG:HDL-C ratio in 402,398 Europeans within the UK Biobank. We identified 369 independent SNPs, of which 114 had a false discovery rate-adjusted P value < 0.05 in other genome-wide studies of IR making them high-confidence IR-associated loci. Seventy-two of these 114 loci have not been previously associated with IR. These 114 loci cluster into five groups upon phenome-wide analysis and are enriched for candidate genes important in insulin signaling, adipocyte physiology and protein metabolism. We created a polygenic-risk score from the high-confidence IR-associated loci using 51,550 European individuals in the Michigan Genomics Initiative. We identified associations with diabetes, hyperglyceridemia, hypertension, nonalcoholic fatty liver disease and ischemic heart disease. Collectively, this study provides insight into the genes, pathways, tissues and subtypes critical in IR.

Dysregulation of mitochondrial dynamics mediated aortic perivascular adipose tissue-associated vascular reactivity impairment under excessive fructose intake

Excessive fructose intake presents the major risk factor for metabolic cardiovascular disease. Perivascular adipose tissue (PVAT) is a metabolic tissue and possesses a paracrine function in regulating aortic reactivity. However, whether and how PVAT alters vascular function under fructose overconsumption remains largely unknown. In this study, male Sprague-Dawley rats (8 weeks old) were fed a 60% high fructose diet (HFD) for 12 weeks. Fasting blood sugar, insulin, and triglycerides were significantly increased by HFD intake. Plasma adiponectin was significantly enhanced in the HFD group. The expression of uncoupling protein 1 (UCP1) and mitochondrial mass were reduced in the aortic PVAT of the HFD group. Concurrently, the expression of peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) and mitochondrial transcription factor A (TFAM) were suppressed. Furthermore, decreased fusion proteins (OPA1, MFN1, and MFN2) were accompanied by increased fission proteins (FIS1 and phospho-DRP1). Notably, the upregulated α-smooth muscle actin (α-SMA) and osteocalcin in the PVAT were concurrent with the impaired reactivity of aortic contraction and relaxation. Coenzyme Q10 (Q, 10 mg/100 mL, 4 weeks) effectively reversed the aforementioned events induced by HFD. Together, these results suggested that the dysregulation of mitochondrial dynamics mediated HFD-triggered PVAT whitening to impair aortic reactivity. Fortunately, coenzyme Q10 treatment reversed HFD-induced PVAT whitening and aortic reactivity.

Diabetes Mellitus, Obesity, and Metabolic Dysregulation as Risk Factors for Metabolic Dysfunction-Associated Steatotic Liver Disease

Background and Aim: New nomenclature defines metabolic dysfunction-associated steatotic liver disease (MASLD) as hepatic steatosis with at least one of the following, i.e., type 2 diabetes mellitus, obesity, and metabolic dysregulation. This study aimed to determine the risk factor profile of individual components of MASLD. Methods: Three hundred and forty-one patients attending the master health checkup between October 2022 and December 2022 at two centers were screened for fatty liver (FL) and assessed for three metabolic states: type 2 diabetes mellitus (T2DM), overweight/obesity (body mass index [BMI] ≥23 kg/m2), and metabolic dysregulation (Asia Pacific Association Study for Liver [APASL] criteria: 3 of the 5 criteria), i.e., waist circumference (WC) ≥90 cm (men); 80 cm (women); blood pressure &gt;130/85 mm Hg, triglyceride (TGL) &gt;150 mg/dL, high-density lipoprotein &lt;40 mg/dL (men); &lt;50 mg/dL (women), prediabetes (blood sugar [fasting] 100≤ to ≤125 mg/dL, or postprandial 140≤ to ≤199 mg/dL, and glycated hemoglobin 5.7≤ to ≤6.4%. Results: Of the 190 patients with FL, 172 patients had metabolic dysfunction (90.5%), 164 had raised BMI (86.3%), and 69 had diabetes (36.3%). MeS in combination with high BMI was present in 97 patients (51.1%) and all three were present in 52 (27.4%). Twenty-three patients (12.1%) had lean type MASLD, i.e., BMI &lt;23 kg/m2. In the absence of FL (151 patients), 104 patients (54.7%) had MeS, 34 (22.5%) had T2DM, and 91 (60.3%) had raised BMI. Significant contributors to MAFLD were overweight/obese BMI ≥23 (odds ratio [OR]: 4.16), WC (men) (OR: 5.61), diabetes mellitus (OR: 1.96), and elevated S. TGL levels (OR: 4.77). Conclusion: Diagnosis of MASLD based on the presence of definite indicators of metabolic dysfunction can aid in the identification of at-risk patient groups and thereby tailor management in these patients.

Association of Body Mass Index with Outcomes in Patients with Atrial Fibrillation: Analysis from the (JoFib) Registry.

Atrial fibrillation (AF) accounts for the majority of arrhythmias affecting adults. It is associated with an increased mortality and various complications. Obesity being a major risk factor of cardiovascular and metabolic diseases including AF has always been connected to the overall burden of AF, but its role in the development of AF complications remains unclear. Our study aims to evaluate the impact of obesity on the complications of AF in Jordanian patients to establish a proper prognosis since studies regarding this topic in the Middle East are scant. This study analyzed data from the Jordanian AF study (JoFib), which enrolled Jordanians with AF. Clinical characteristics were compared among patients who developed complications and those who did not. A binary logistic regression analysis was conducted to identify factors associated with AF complications development. 1857 patients were enrolled. There was no significant difference in BMI value between patients who developed complications and those who did not. Male sex, old age, hypertension, diabetes mellitus, and higher risk scores were associated with increased odds of developing complications. The oral anticoagulant use was found to be protective. Smoking had no significant effect on odds of complications. The study concludes that increased BMI is not significantly associated with a reduced risk of developing AF complications. Further research with longer follow-up and larger sample sizes is needed to confirm these results.

Association between menstrual cycle phase and metabolites in healthy, regularly menstruating women in UK Biobank, and effect modification by inflammatory markers and risk factors for metabolic disease

BackgroundPreliminary evidence demonstrates some parameters of metabolic control, including glycaemic control, lipid control and insulin resistance, vary across the menstrual cycle. However, the literature is inconsistent, and the underlying mechanisms remain uncertain. This study aimed to investigate the association between the menstrual cycle phase and metabolites and to explore potential mediators and moderators of these associations.MethodsWe undertook a cross-sectional cohort study using UK Biobank. The outcome variables were glucose; triglyceride; triglyceride to glucose index (TyG index); total, HDL and LDL cholesterol; and total to HDL cholesterol ratio. Generalised additive models (GAM) were used to investigate non-linear associations between the menstrual cycle phase and outcome variables. Anthropometric, lifestyle, fitness and inflammatory markers were explored as potential mediators and moderators of the associations between the menstrual cycle phase and outcome variables.ResultsData from 8694 regularly menstruating women in UK Biobank were analysed. Non-linear associations were observed between the menstrual cycle phase and total (p < 0.001), HDL (p < 0.001), LDL (p = 0.012) and total to HDL cholesterol (p < 0.001), but not glucose (p = 0.072), triglyceride (p = 0.066) or TyG index (p = 0.100). Neither anthropometric, physical fitness, physical activity, nor inflammatory markers mediated the associations between the menstrual cycle phase and metabolites. Moderator analysis demonstrated a greater magnitude of variation for all metabolites across the menstrual cycle in the highest and lowest two quartiles of fat mass and physical activity, respectively.ConclusionsCholesterol profiles exhibit a non-linear relationship with the menstrual cycle phase. Physical activity, anthropometric and fitness variables moderate the associations between the menstrual cycle phase and metabolite concentration. These findings indicate the potential importance of physical activity and fat mass as modifiable risk factors of the intra-individual variation in metabolic control across the menstrual cycle in pre-menopausal women.

Associations of polychlorinated biphenyls and organochlorine pesticides with metabolic dysfunction-associated fatty liver disease among Chinese adults: Effect modification by lifestyle

Exposure to environmental pollutants and unhealthy lifestyles are key risk factors for metabolic dysfunction-associated fatty liver disease (MAFLD). While previous studies have suggested links between exposure to organochlorine pesticides (PCBs) and organochlorine pesticides (OCPs) and MAFLD, the results have been inconsistent. Furthermore, the combined effects of PCBs and OCPs on MAFLD and whether lifestyle factors can modify the associations remain unknown. Therefore, this study aimed to investigate the individual and joint effects of PCBs and OCPs on MAFLD and explore the potential modifying role of lifestyle. The study included 1923 participants from Wuhan, China. MAFLD was diagnosed based on ultrasonically diagnosed hepatic steatosis and the presence of overweight/obese, diabetes mellitus, or metabolic dysregulation. Healthy lifestyle score was determined by smoking, alcohol consumption, physical activity, and diet. Logistic regression and weighted quantile sum (WQS) were used to assess associations of individual and mixture of PCBs/OCPs with MAFLD. To explore the potential lifestyle modification, joint associations of PCBs/OCPs and lifestyle on MAFLD were conducted. Single-pollutant analysis showed positive associations of p,p′-DDE, β-HCH, PCB-153, and PCB-180 with MAFLD, with ORs (95% CIs) of 1.18 (1.05, 1.33), 1.57 (1.20, 2.05), 1.45 (1.14, 1.83), and 1.42 (1.12, 1.80), respectively. WQS regression demonstrated a harmful effect of PCBs/OCPs mixture on MAFLD (OR = 1.73, 95% CI = 1.24, 2.43), with β-HCH, p,p’-DDE, and PCB-180 being the major contributors. In the joint association analysis, participants with both high PCBs/OCPs exposure and unhealthy lifestyle have the highest odds of MAFLD. In conclusion, exposure to the mixture of PCBs and OCPs was positively correlated with MAFLD, and adopting a healthy lifestyle can mitigate the adverse impact.

Liver-Selective Imidazolopyrazine Mitochondrial Uncoupler SHD865 Reverses Adiposity and Glucose Intolerance in Mice.

Excess body fat is a risk factor for metabolic diseases and is a leading preventable cause of morbidity and mortality worldwide. There is a strong need to find new treatments that decrease the burden of obesity and lower the risk of obesity-related comorbidities including cardiovascular disease and type 2 diabetes. Pharmacologic mitochondrial uncouplers represent a potential treatment for obesity through their ability to increase nutrient oxidation. Herein, we report the in vitro and in vivo characterization of compound SHD865, the first compound to be studied in vivo in a newly discovered class of imidazolopyrazine mitochondrial uncouplers. SHD865 is a derivative of the furazanopyrazine uncoupler BAM15. SHD865 is a milder mitochondrial uncoupler than BAM15 that results in a lower maximal respiration rate. In a mouse model of diet-induced adiposity, six-week treatment with SHD865 completely restored normal body composition and glucose tolerance to levels like those of chow-fed controls without altering food intake. SHD865 treatment also corrected liver steatosis and plasma hyperlipidemia to normal levels comparable with chow-fed controls. SHD865 has maximal oral bioavailability in rats and slow clearance in human microsomes and hepatocytes. Collectively, these data identify the potential of imidazolopyrazine mitochondrial uncouplers as drug candidates for the treatment of obesity-related disorders.

Anti-Hyperglycemic Effects of Bioactive Compounds in the Context of the Prevention of Diet-Related Diseases.

Diet-related diseases are health conditions primary caused by poor nutrition. These diseases encompass obesity, type 2 diabetes, cardiovascular diseases, osteoporosis, and certain types of cancer. Functional foods and nutraceuticals offer a promising dietary approach to addressing diet-related diseases across various clinical contexts. The bioactive compounds found in these foods are the subject of intensive studies aimed at discovering their anti-hyperglycemic effects, which are beneficial in alleviating chronic diseases and protecting human health. Hyperglycemia is a common risk factor for metabolic disease and mortality worldwide. Chronic hyperglycemic states can lead to many long-term complications, such as retinopathy, neuropathy, kidney disease, heart disease, cancer, and diabetes. This review explores the potential anti-hyperglycemic effects of bioactive compounds, specifically flavonoids and phenolic acids, and their proposed roles in mitigating chronic diseases and promoting human health. By thoroughly examining the existing literature, we investigated the potential anti-hyperglycemic effects of these bioactive compounds and their proposed roles in managing chronic diseases. The goal of this paper was to enhance our comprehension of how these compounds modulate glucose transporters, with the ultimate aim of identifying effective strategies for the prevention and treatment of diet-related diseases. Overall, this review investigated the use of bioactive compounds from functional foods as potential inhibitors of glucose transporters in the context of prevention/treatment of diet-related diseases.