Leptin/Ghrelin Axis and Antibodies Reactive to Both Hormones in Relation to Metabolic Syndrome Components in Mexican Children
Metabolic syndrome (MetS) in children is a rising health issue that is strongly associated with cardiovascular diseases and type 2 diabetes mellitus development. Low-affinity antibodies reactive to leptin and ghrelin are suggested to regulate hormone stability and function; nevertheless, the role of the leptin/ghrelin axis and antibodies reactive to both hormones in relation to MetS or its components in the pediatric population remains unknown. Fifty-eight children (7-12 years) were included and categorized according to the presence of one or more criteria for the diagnosis of MetS or according to body mass index. Body composition, biochemical variables, and metabolic risk indexes were determined. Antibodies reactive to leptin and ghrelin were quantified by an in-house enzyme-linked immunosorbent assay test. Ratios of leptin/ghrelin hormones and anti-leptin/anti-ghrelin immune complexes were obtained. The biochemical variables glucose ( = 0.0009), insulin ( = 0.0001), leptin ( = 0.0036), HOMA-IR (homeostatic model assessment for insulin resistance) ( < 0.0001), and plasma atherogenic index ( < 0.0001) were significantly higher in children with two or three components of MetS (MetS 2-3) in comparison to children with none or one component (MetS 0-1). Ratios of leptin/ghrelin ( = 0.0307) and anti-leptin/anti-ghrelin immune complexes ( = 0.0338) were higher in MetS 2-3 group versus MetS 0-1 group. In MetS 2-3 group, both insulin ( = 0.4361, = 0.0293) and HOMA-IR ( = 0.4761, = 0.0161) were positively correlated with the leptin/ghrelin hormone ratio. The higher leptin/ghrelin hormone ratio scores observed in MetS 2-3 group, along with their correlation with insulin levels and HOMA-IR, highlight the role of leptin and ghrelin on insulin sensitivity and metabolic regulation. An increased ratio of anti-leptin/anti-ghrelin immune complexes suggests affinity changes in these antibodies that may lead to alterations in hormone function.
Confusion Concerning the Calculation of the Triglyceride-Glucose Index: An Urgent Need for Clarity
Shift Work Increases the Risk of Circadian Syndrome Rather than Metabolic Syndrome: A Cross-Sectional Study of NHANES 2005-2010
Shift work disrupts sleep-wake cycles and may lead to adverse health outcomes, including cardiovascular disease and metabolic disorders. This study examines the association between shift work and the risks of metabolic syndrome (MetS) and circadian syndrome (CircS) in U.S. workers. We analyzed data from 4173 participants aged 18 and above from the National Health and Nutrition Examination Survey (NHANES) spanning 2005-2010. Shift work status was determined based on work hours, and MetS and CircS were defined using established criteria. Statistical analyses included weighted multivariate logistic regression models, weighted multivariate linear regression models, and inverse probability weighted propensity score matching to ensure accurate comparison between shift and nonshift workers. The study found no significant association between shift work and the prevalence of MetS. However, shift workers exhibited a higher prevalence of CircS compared with nonshift workers. This association was more pronounced in specific subgroups, including those under 60 years of age and various ethnicities. The study highlights the heightened risk of CircS among shift workers, underscoring the potential impact of shift work on circadian rhythm disruptions. Shift work is associated with an increased risk of CircS but not MetS, according to NHANES 2005-2010 data.
Truncated Albumins as Novel Surrogate Biomarkers in Diabetes Therapy: Epiphenomena and Potential Clinical Applications
Among various albumin posttranslational modifications (PTMs), N- and C-terminal truncations (HSA-DA and HSA-L) have also shown biomarker potential in disease states. We examined albumin truncation longitudinal trends and correlations during diabetes therapy toward possible future clinical applications. In a preliminary longitudinal therapy investigation, mass spectrometry was employed to track PTMs of human serum albumin (HSA), including glycation (GA), cysteinylation (CA or HNA1; reversible), di/trioxidation (OA or HNA2; irreversible), and truncation (TA). These modifications were correlated with ongoing therapy in four distinct subject groups: type 1 diabetes (T1DM), type 2 diabetes (T2DM), prediabetes-obesity (PDOB), and healthy controls (NORM), observed over a follow-up period extending up to 280 days. Diabetes was associated with significant reduction ("deficiency") of measured albumin truncations (For HSA-DA: T2DM = 0.32 ± 0.3%, = 2E-08; T1DM = 1.02 ± 0.4%, = 3E-05; PDOB = 1.61 ± 0.2%, = 0.004; compared to NORM = 2.08 ± 0.2%). Albumin truncation reduction was more striking in T2DM (HSA-DA: T2DM vs. T1DM: = 0.004). Improvements in glycemic control and decrease of albumin glycation during diabetes therapy were associated with concomitant increase of albumin truncations toward the "healthy" normal ranges, and vice versa ("mirror image" trends). Accordingly, albumin truncation correlated inversely with albumin glycation (HSA-DA vs. GA: R = -0.53, = 1E-09). The "epiphenomenon" of albumin truncation (reflecting the severity of mean hyperglycemia and also insulin resistance) can possibly provide novel, sensitive, and complementary biomarkers ( via simpler HSA-DA peptide fragment immunoassays) to monitor efficacy of diabetes therapy and also progression from "healthy" to prediabetes and type 2 diabetes, highlighting potential diagnostic and prognostic utility in clinical diabetes care.
Effect of Real-Time Continuous Glucose Monitoring Versus Flash Glucose Monitoring on Glycemic Control in Adults with Type 1 Diabetes Mellitus: A Systematic Review and Meta-Analysis
This meta-analysis aimed to compare the effect of the real-time continuous glucose monitoring (rt-CGM) and flash glucose monitoring (FGM) on glycemic control in adults with type 1 diabetes mellitus (T1DM). A systematic literature search of all relevant studies comparing the clinical effectiveness of rt-CGM and FGM in adults with T1DM on Cochrane Library, PubMed, Embase, Web of Science, and Scopus from January 2015 to June 2023 was performed. The primary endpoints were glycated hemoglobin (HbA1c) and TIR (time in range). Secondary endpoints included time below range [TBR (<3.9 mmol/L) and (<3.0 mmol/L)], time above range [TAR (>10.0 mmol/L) and (>13.9 mmol/L)], mean glucose, and glycemic variability (GV) [standard deviations (SD) and coefficient of variation (CV)]. Six studies with 1516 TIDM patients, including three randomized controlled trials and three observational studies, were enrolled in this meta-analysis. Compared to FGM, rt-CGM led to greater glycemic control, represented by higher TIR (%, 3.9 ∼ 10 mmol/L) (SMD = 0.59, 95% CI: 0.37 ∼ 0.81, < 0.001), decreased TBR (%, <3.9 mmol/L) (SMD = -1.45, 95% CI: -2.33 ∼ -0.57, = 0.001), decreased TAR [(%, >10.0 mmol/L) (SMD = -0.38, 95% CI: -0.71 ∼ -0.04, = 0.03) and (%, >13.9 mmol/L) (SMD = -0.42, 95% CI: -0.79 ∼ -0.04, = 0.03), respectively], lower mean glucose (SMD = -0.18, 95% CI: -0.31 ∼ -0.06, = 0.003), decreased SD (SMD = -0.70, 95% CI: -1.09 ∼ -0.31, < 0.001), and decreased CV (SMD = -0.76, 95% CI: -1.05 ∼ -0.47, < 0.001). However, there was no difference in lowering HbA1c and TBR (%, <3.0 mmol/L) between groups. The rt-CGM outperformed FGM in improving several key CGM metrics among adults with T1DM, but there is no significant difference in HbA1c and TBR (<3.0 mmol/L).
A Novel Insight into Postmenopausal Hypercholesterolemia: Carnitine as a Key Player
Postmenopausal women (post-MW) are at a heightened risk of cardiovascular diseases, including hypercholesterolemia. This study aimed to investigate metabolomic variations to identify potential markers and targets for postmenopausal hypercholesterolemia. Sixty-two female volunteers aged 40-65 were recruited for this study. Metabolomic analysis using the Ultra-Performance Liquid Chromatography Quadrupole Orbitrap Mass Spectrometry (UPLC-Q-Orbitrap MS) platform was conducted to investigate changes in endogenous substances in premenopause ( = 25) and postmenopause ( = 37) women. Following ovariectomy surgery, menopausal mice were monitored for changes in their biomarker levels, and the integrity of the large artery walls in each treatment group was observed through hematoxylin and eosin staining. cellular models were utilized to assess variations in lipid metabolism, reactive oxygen species (ROS) levels, and changes in the levels of superoxide dismutase and glutathione peroxidase enzymes in different cell groups postintervention using Western blot analysis. Treatment with carnitine in postmenopausal mouse models led to increased plasma cholesterol and carnitine levels, as well as indicators of arterial sclerosis. In HepG2 cells, carnitine treatment resulted in heightened lipid levels, elevated ROS production, and decreased antioxidant enzyme levels. The findings suggest that carnitine may serve as a potential risk marker or therapeutic target for postmenopausal hypercholesterolemia. This study provides valuable insights into cardiovascular conditions in post-MW and offers new avenues for therapeutic interventions. Continued research in this area is crucial to enhance our understanding of cardiovascular diseases in post-MW and to explore additional treatment options.
Cortisol/Cortisone Ratio in Youth with Obesity One Year Following Sleeve Gastrectomy
Glucocorticoid metabolites are associated with body composition measures and are altered with weight status. Metabolic and bariatric surgery (MBS) results in significant changes in weight and body composition. However, MBS effects on glucocorticoid metabolites are unknown. To evaluate (i) changes in the cortisol/cortisone ratio in youth with obesity 12 months after sleeve gastrectomy (SG) compared with nonsurgical controls with obesity (NS), and (ii) associations of these changes with body composition changes. A total of 38 participants 13-25 years old with obesity (29 female) were followed for 12 months. Half underwent SG, and the other half were followed with routine care (nonsurgical, NS). Fasting blood was assessed for cortisol and cortisone using liquid chromatography-mass spectroscopy as part of metabolomic analysis, and the cortisol/cortisone ratio was calculated. A single-slice MRI of the abdomen was performed to assess subcutaneous and visceral adipose tissue (SAT, VAT. Hepatic steatosis was assessed by computed tomography (CT). SG did not differ from NS for baseline clinical characteristics, other than the mean age (SG 18.0 ± 0.46 vs. NS 16.6 ± 0.50 years, = 0.041), BMI (BMI, 47.23 ± 1.5 vs. 41.32 ± 1.1 kg/m, = 0.003) weight and VAT, which were higher in SG. Significant reductions were noted over 12 months in BMI, BMI z-score, VAT, and SAT within the SG versus NS groups ( ≤ 0.001). Over 12 months, groups did not differ for changes in cortisol/cortisone ratio after controlling for age at baseline ( = 0.293). The ratio trended to decrease within the SG group [-1.40 (-5.08, 0.06), = 0.080], particularly among those that had completed puberty ( = 0.048). No associations were found between changes in the cortisol/cortisone ratio and changes in body composition. The cortisol/cortisone ratio trended to decrease 12 months following SG. However, no associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Studies with larger numbers of participants are necessary to confirm these findings.
Association Between Remnant Cholesterol and Nonalcoholic Fatty Liver Disease: A Systemic Review and Meta-Analysis
Lipid disorders are related to the risk of nonalcoholic fatty liver disease (NAFLD). Remnant cholesterol (RC), a nonclassical and once-neglected risk factor for NAFLD, has recently received new attention. In this study, we assessed the relationship between the RC levels and NAFLD risk. We searched across PubMed, Web of Science, Embase, Cochrane Library, and China National Knowledge Infrastructure, with no restrictions on publication languages. Retrospective cohort studies and cross-sectional studies were enrolled from the inception of the databases until August 6, 2023. A random-effect model was applied to construct the mean difference, and a 95% confidence interval was applied to assess the relationship between the RC levels and NAFLD risk. We used two methods to estimate RC levels: Calculated-1 subtracts low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol from total cholesterol; Calculated-2 uses the Friedewald formula for LDL-C when triglycerides are <4.0 mmol/L, otherwise directly measured. A total of 265 published studies were selected through preliminary retrieval. Of these, six studies met the inclusion requirements and were enrolled in the meta-analysis. The RC level in the NAFLD group was significantly higher than that in the non-NAFLD group (mean difference: 0.18, 95% confidence interval: 0.10-0.26, < 0.00001). We conducted subgroup analyses of computational methods and geographic regions. Notably, in the subgroup analysis of Calculation Method 2, the NAFLD group had significantly higher RC levels than the non-NAFLD group. On the other hand, in Calculation Method 1, the difference between the two groups was insignificant. In both the Asian and non-Asian populations, the RC levels were significantly higher in the NAFLD group than in the non-NAFLD group. The association of RC with an increased NAFLD risk was not dependent on the triglyceride. This meta-analysis suggests that elevated RC levels are associated with an increased risk of NAFLD. In addition to the conventional risk factors for fatty liver, clinicians should be concerned about the RC levels in the clinic.
Metabolic Syndrome and the Risk of Alzheimer's Disease: A Meta-Analysis
The relationship between metabolic syndrome (MetS) and the risk of Alzheimer's disease (AD) remains unclear. This meta-analysis aims to clarify the prospective association between MetS and AD risk and to explore how individual MetS components contribute to this relationship. Comprehensive searches of MEDLINE, Web of Science, and Embase were conducted up to April 12, 2024. Relevant prospective cohort studies were included. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to assess the associations. A random-effects model was used to incorporate the potential impact of heterogeneity. Six prospective cohort studies with seven datasets, including 484,994 participants and a follow-up of 3.5 to 13.0 years, were included. The pooled analysis showed no significant association between MetS and AD risk (HR: 0.96, 95% CI: 0.89-1.04, = 0.37; = 0%). Sensitivity and subgroup analyses confirmed these findings. Individual MetS components exhibited varied effects as follows: abdominal obesity was linked to a reduced AD risk (Risk ratio (RR): 0.70, 95% CI: 0.56-0.88, = 0.002), whereas high blood pressure (BP) (RR: 1.15, 95% CI: 1.04-1.27, = 0.007) and hyperglycemia (RR: 1.24, 95% CI: 1.08-1.42, = 0.002) were associated with an increased risk. Low high-density lipoprotein cholesterol and high triglycerides showed no significant associations. This meta-analysis found no significant overall association between MetS and AD risk. However, specific MetS components, such as abdominal obesity, high BP, and hyperglycemia, may influence AD risk differently.
Efficacy of Alogliptin/Metformin Fixed-Dose Combination Tablets and Vildagliptin/Metformin Fixed-Dose Combination Tablets on Glycemic Control in Real-World Clinical Practice for the Patients with Type 2 Diabetes: A Multicenter, Open-Label, Randomized, Parallel Group, Comparative Trial
This study was aimed to compare the efficacy of two combination tablets of dipeptidyl peptidase-4 (DPP-4) inhibitors and metformin with different dosages, alogliptin/metformin (AM) and vildagliptin/metformin (VM), on glycemic control in patients with type 2 diabetes (T2D). This was a prospective, multicenter, open-label, randomized, parallel group, comparative trial. After a run-in period of treatment with metformin alone, a total of 59 Japanese outpatients with T2D, aged 20-79 years with glycated hemoglobin (HbA1c) levels of 6.5%-10% were randomly assigned to 12-week AM treatment, alogliptin 25 mg/metformin 500 mg combination tablet orally once a day, or VM treatment, vildagliptin 50 mg/metformin 250 mg combination tablet orally twice a day. The primary endpoints were the changes in HbA1c and fasting plasma glucose (FPG) levels from baseline to week 12 between the two groups. Blinded intermittently scanned continuous glucose monitoring (isCGM) was performed between weeks 10 and 12. The incidence of adverse events during the study was also evaluated. In all, 52 participants were analyzed. Significant decreases in HbA1c and FPG levels from baseline to week 12 were observed in both treatment groups. However, there were no significant differences between the AM and VM groups in the change in HbA1c level (-0.3% and -0.4%, = 0.309) or the FPG level (-9.0 and -15.0 mg/dL, = 0.789). The isCGM revealed that both treatments achieved the recommended glycemic target range. No adverse events, such as severe hypoglycemia, were observed in either group. We concluded that there were no significant differences in the efficacy of two combination tablets of DPP-4 inhibitors and metformin with different dosages on glycemic control in patients with T2D.
Methylation Patterns of Diabetes and Obesity Susceptibility Genes in Gestational Diabetes Mellitus: A Cross-Sectional Analysis from Karachi, Pakistan
Women with gestational diabetes mellitus (GDM) and their offspring have an increased risk of adverse perinatal and long-term health outcomes, which may be attributable to epigenetic modification of diabetes and obesity susceptibility genes. We aimed to investigate the methylation patterns of eight genes in GDM and normoglycemic (NG) mothers, and their respective offspring. This cross-sectional study, conducted at Aga Khan University from August 2019 to December 2022, recruited pregnant women in the first trimester of gestation from the outpatient obstetrics clinic. Participants were classified as NG or GDM based on the Society of Obstetricians and Gynecologists Pakistan. Venous blood samples were collected from mothers and cord blood from neonates. Peripheral blood mononuclear cells were used for DNA extraction and methylation analysis using methylation-specific PCR. Maternal and neonatal clinical data were recorded. Statistical analysis was performed using R, including binary logistic regression to assess the association between various gene methylation levels and GDM. The study found that GDM mothers had significantly higher fasting blood glucose, 2-hr OGTT, and serum carboxymethyl lysine (CML) levels compared to NG mothers, but no significant differences in neonatal birth weight or serum CML levels. Chemerin methylation was significantly lower in GDM mothers and their babies, while , and methylation levels were higher in GDM offspring compared to NG offspring. GDM mothers also had higher methylation levels of brain-derived neurotrophic factor gene (). Multivariable binary logistic regression identified methylation levels of maternal BDNF and neonatal MTNR1B to be independently associated with GDM. Our study shows a trend of epigenetic modifications in both GDM mothers and their offspring in various genes related to metabolism and inflammation, suggesting an intergenerational transmission of increased risk of developing metabolic disorders. These findings emphasize the need for high throughput studies, early screening, tight glucose control during pregnancy, and postnatal follow-up to mitigate long-term health risks.
Normative Values and Anthropometric Prediction Models for Lean Mass and Fat Mass in the Northeastern Thai Population
Data on reference values for lean mass (LM) and fat mass (FM) in the Southeast Asian populations are currently lacking. Therefore, we aimed to estimate the normative values and generate anthropometric prediction models for LM and FM in the Thai population. Consecutive community-dwelling individuals aged 20-90 years were recruited from Srinagarind Hospital, Khon Kaen, Thailand, between 2010 and 2015. LM and FM were measured using dual energy X-ray absorptiometry. Age and sex stratified percentile of LM and FM were presented. Anthropometric prediction models for LM and FM were developed by using linear regression to generate competing models. A total of 832 individuals (334 males and 498 females) were included in the study. The mean ± SD age, LM, and FM were 50.0 ± 16.2 years, 38.9 ± 8.0 kg, and 15.5 ± 7.7 kg, respectively. LM decreased with age from 49.4 kg in 20-29 years group to 42.3 kg in ≥70 years group in male and 34.6 kg in 30-39 years group to 30.8 kg in ≥70 years group in females. FM has an inverse U-shaped association with age, which peaked at 11.9 kg in 60-69 years group in males and 20.7 kg in 50-59 years group in females. Among the various anthropometric models, the models incorporating age, sex, weight, and height were considered the best fit for predicting both LM and FM. In the Thai population, peak LM was reached during early adulthood and decline with age, whereas FM showed an inverse U-shaped association with age. The prediction models incorporating age, sex, weight, and height were proposed as practical tools for assessing LM and FM in clinical practice.
The Magnetic Resonance Image-Arterial Spin Labeling Characteristic of Nonketotic Hyperglycemic Hemichorea in an Elderly Type 2 Diabetic Female Patient
Nonketotic hyperglycemia-induced hemichorea is a rare condition of type 2 diabetes. It is characterized by hyperglycemia with the symptom traced to the basal ganglion like hemichorea or hemiballism, with the hyperintensity within basal ganglion presented in computed tomography (CT) or hyper signal in T1-weighted magnetic resonance image (MRI). It was also confirmed with a relatively better prognosis in that the symptoms of these patients could be relieved after the alleviation of hyperglycemia. However, the exact pathophysiology or mechanism of this condition currently was unclear. Besides, the duration of improvement in tomography as far was varied. In the present study, we reported an elderly female patient who tested with nonketotic hyperglycemia (random blood glucose of fingertips was 19 mmol/L or 342 mg/dL, blood ketone was 0.1 mmol/L) with the symptoms of dysphoria and mild chorea of left low limb, the MRI and CT showed contralateral striatopathy. Her condition achieved alleviation after the normalization of blood glucose. We subsequently rechecked her MRI in arterial spin labeling sequence which showed the hypoperfusion in the right basal ganglion rather than the opposite. Therefore, we suppose the hyperglycemia could induce temporary hypoperfusion in the basal ganglion associated with motor dysfunction which is manifested by hemichorea or hemiballism.
Physical Activity before and After Bariatric Surgery
Lifestyle changes including reduced calorie intake and increased physical activity (PA) improve the prognosis associated with bariatric surgery (BS) and metabolic indices. Early implementation of exercise leads to improved physical performance, better glycemic control and lipid profile, reduces the risks associated with anesthesia, and accelerates recovery from surgery. Undertaking systematic exercise after BS is associated with a better quality of life, improves insulin sensitivity, results in additional weight loss, reduces adverse effects on bone mass, and results in better body composition. The aim of this review was to summarize recommendations for physical activity in patients undergoing BS and to highlight the key role of physical activity in this patient group.
Comparison Between SGLT2 Inhibitors and Lactation: Implications for Cardiometabolic Health in Parous Women
Sodium-glucose cotransporter-2 (SGLT2) inhibition and lactation result in the excretion of large amounts of glucose in urine or milk and are associated with a lower risk of cardiovascular events. The respective mechanisms behind this association with cardiovascular protection are not clear. This review compares the contribution of noninsulin-mediated glucose transport during pharmacologic inhibition of SGLT2 with noninsulin-mediated glucose transport during lactation in terms of the implications for the cardiometabolic health of parous women. The search topics used to obtain information on SGLT2 inhibitors included mechanisms of action, atherosclerosis, and heart failure. The search topics used to obtain information on lactation included cardiovascular health and milk composition. Subsequent reference searches of retrieved articles were also used. Active treatment with SGLT2 inhibitors affects glucose and sodium transport in the kidneys and predominantly protects against hospitalization for heart failure soon after the onset of therapy. Active lactation stimulates glucose transport into the mammary gland and improves subclinical and clinical atherosclerotic vascular disease years after delivery. Both SGLT2 inhibitors and lactation have effects on a variety of glucose transporters. Several mechanisms have been proposed to explain the cardiometabolic benefits of SGLT2 inhibition and lactation. Learning from the similarities and differences between both processes will advance our understanding of cardiometabolic health for all people.
Association of Dietary Vitamin C Intake with the Risk of Metabolic Syndrome Among Adults: NHANES 2007-2018
There has been discussion over the association between vitamin C intake and the risk of metabolic syndrome (MetS). This study examined the relationship between dietary vitamin C intake and the risk of MetS in a sizable adult American population. We examined the relationship between dietary vitamin C intake and the risk of MetS in 12,943 persons from the 2007 to 2018 National Health and Nutrition Examination Survey (NHANES). This association was then evaluated using logistic regression and restricted cubic spline models. Sex and age-based subgroup analyses were carried out. According to the results of the multiple regression model, the risk of MetS was inversely correlated with dietary vitamin C intake, vitamin C intake derived from fruits and vegetables. The adjusted results (odds ratios with 95% confidence intervals) for the highest versus lowest tertile were 0.80 (0.68-0.93), 0.86 (0.75-0.98), and 0.80 (0.69-0.93). Subgroup analyses further showed that the negative correlation of dietary vitamin C intake with the risk of MetS was particularly pronounced among females, those in the 20-39 age group, and those in the ≥60 age group. The dose-response relationship's findings indicated that vitamin C from diet and fruits had a nonlinear correlation with the risk of MetS, whereas vitamin C from vegetables had a linear correlation. The risk of MetS in adult Americans was found to be negatively correlated with dietary vitamin C intake, particularly from fruits and vegetables.
Association Between Relative Grip Strength, Insulin Resistance, and Nonalcoholic Fatty Liver Disease Among Middle-Aged and Older Adults: A Prospective Cohort Study
This study aims to investigate the combined association between insulin resistance (IR) levels, relative grip strength (RGS), and the incidence of nonalcoholic fatty liver disease (NAFLD), stratified by sex, using longitudinal data. The study included 1702 adult participants aged 51-88 years who completed surveys in both 2013-2014 and during a subsequent follow-up in 2019-2020. NAFLD was assessed using the hepatic steatosis index, and RGS was measured using the JAMA-5030J1 equipment (SAEHAN, Korea). To assess the interaction between RGS and IR levels and their impact on NAFLD risk, we employed a proportional hazards Cox regression model. Hazard ratios (HR) and 95% confidence intervals (95% CI) were calculated for NAFLD incidence. After adjusting for various confounding variables, we observed a significant decrease in NAFLD risk in the middle RGS group (HR = 0.70, 95% CI = 0.53-0.93) and high RGS group (HR = 0.31, 95% CI = 0.22-0.44) compared to the low RGS group. In addition, significant sex differences were noted in the relationship between IR, RGS levels, and NAFLD incidence across different groups. This study highlights that higher RGS levels are independently associated with a reduced risk of developing NAFLD. Notably, RGS emerges as a predictive indicator for assessing NAFLD risk.
Effects of Weight Loss and Weight Maintenance on Lipoprotein Insulin Resistance Scores in Adults with Overweight and Obesity
An elevated lipoprotein insulin resistance (LP-IR) score corresponds to insulin resistance in adults with overweight and obesity, yet data are lacking regarding the impact of exercise interventions on LP-IR. The purpose of this secondary analysis was to evaluate the effects of a weight loss and weight maintenance intervention on LP-IR score in adults with overweight and obesity. Thirty sedentary adults with overweight and obesity completed a 10-week OPTIFAST weight loss program with supervised aerobic exercise to achieve clinical weight loss (CWL) (≥7% from baseline). Aerobic exercise volume increased weekly until 700 MET min/week was reached. Participants who reached CWL were randomized to groups at volumes at either physical activity (PA-REC) or weight maintenance (WM-REC) recommendations (weeks 11-28). Plasma blood samples were analyzed via nuclear magnetic resonance spectroscopy at baseline, after weight loss (week 10), and following weight maintenance (week 28). Following the weight loss phase, on average, participants significantly ( < 0.001) reduced LP-IR score (-12.1 ± 13.5), body weight (-8.9 ± 2.7%), and waist circumference (-7.7 ± 4.1 cm). During the weight maintenance phase, there were no changes in LP-IR score between exercise groups (PA-REC: 4.1 ± 13.6; WM-REC: -2.0 ± 11.2; = 0.7). The PA-REC group had improvements in LP-IR score from baseline (49.8 ± 24.6 to 36.6 ± 27.6, < 0.001), yet there were no within-group changes during the weight maintenance phase ( > 0.05). LP-IR score improved during weight loss in adults with overweight and obesity and were sustained during the weight maintenance phase in the PA-REC group. Aerobic exercise at least at minimum guidelines following CWL can preserve LP-IR score improvements and may indicate a reduced T2DM risk in adults with overweight and obesity.
The Association of the HEPAKID Index with Insulin Sensitivity Index in Obese Adolescents with Metabolic Syndrome
The HEPAKID index, a novel diagnostic tool with a sensitivity of 82% and specificity of 62% for detecting nonalcoholic fatty liver disease in obese adolescents. Our study aimed to explore the potential relationship between the HEPAKID index and risk factors contributing to the development of cardiovascular disease in obese adolescents with metabolic syndrome. This prospective cross-sectional study, conducted at two medical centers from December 2023 to March 2024, included 208 obese adolescents, with a median age of 14.5 years and an average body mass index (BMI) of 30.57 kg/m. Elevated HEPAKID index values were found in obese adolescents with metabolic syndrome, showing positive associations with BMI, waist and hip circumferences, alanine aminotransferase level, fasting insulin, and homeostasis model assessment for insulin resistance. In those with metabolic syndrome, waist circumference (WC) and homeostasis model assessment for insulin resistance were significant independent variables linked to the HEPAKID index, while WC was the sole influencer in the nonmetabolic syndrome group. Multivariate logistic regression highlighted systolic and diastolic blood pressures, triglycerides, high-density lipoprotein cholesterol, and the HEPAKID index as reliable predictors of metabolic syndrome. A predictive cutoff value of 60.84 for the HEPAKID index showed 61.7% sensitivity and 59.1% specificity in identifying metabolic syndrome. Our study highlighted the potential value of the HEPAKID index in combination with other clinical parameters for predicting metabolic syndrome in obese adolescents, underscoring its role as a valuable screening tool. Furthermore, our findings revealed a correlation between the HEPAKID index and insulin sensitivity in this high-risk population.
Factors Associated with Nonalcoholic Fatty Liver Disease in a Non-Overweight/Obese and Overweight/Obese Chinese Population at Risk for Metabolic Syndrome: A Cross-Sectional Multicenter Study
To investigate the association of demographic, clinical, and metabolic factors with nonalcoholic fatty liver disease (NAFLD) in a non-overweight/obese and overweight/obese Chinese population at risk for metabolic syndrome. A cross-sectional multicenter study was conducted using convenience sampling from eight selected counties/cities in Zhejiang, China, between May 2021 and September 2022. Demographics, epidemiological, anthropometric, and clinical characteristics were obtained from a questionnaire. Least absolute shrinkage and selection operator (LASSO)-logistic regression analysis was used to identify the variables associated with NAFLD. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate the diagnostic value and clinical utility of the variables and models. A total of 1739 patients were enrolled in the final analysis, 345 (19.8%) were non-overweight/obese and 1394 (80.2%) were overweight/obese participants. There were 114 (33.0%) and 1094 (78.5%) patients who met the criteria for NAFLD in the non-overweight/obese participants and the overweight/obese participants respectively. Older age, current smoking, higher triglyceride (TG) levels, higher AST levels, higher albumin levels, lower insulin levels, and higher controlled attenuation parameter (CAP) scores were associated with NAFLD in both non-overweight/obese and overweight/obese participants. The combination of TG+CAP scores had strong predictive values for NAFLD, especially in non-overweight/obese (Area Under Curve = 0.812, 95% confidence interval: 0.764-0.863). DCA showed a superior net benefit of the TG+CAP score over other variables or models, suggesting a better clinical utility in identifying NAFLD. More stringent lipid management strategies remain essential, and the convenience and efficacy of transient elastography for liver steatosis should be recognized, especially in the non-overweight/obese population.
Potential of Vitamin D and l-Cysteine Co-supplementation to Downregulate Mammalian Target of Rapamycin: A Novel Therapeutic Approach to Diabetes
Diabetes, a metabolic disease associated with an increased health care burden and mortality, is currently on the rise. Both upregulation of the mammalian target of rapamycin (mTOR) and decreased levels of vitamin D (VD) and l-cysteine (LC) have been associated with diabetes. The overactivation of mTOR leads to insulin desensitization and metabolic dysfunction including uncontrolled hyperglycemia. This review summarizes various studies that have shown an inhibitory effect of VD or LC on mTOR activity. Findings from preclinical studies suggest that optimizing the VD and LC status in patients with diabetes can result in mTOR suppression, which has the potential to protect these individuals from microvascular and macrovascular complications while enhancing the regulation of their blood glucose. Given this information, finding ways to suppress mTOR signaling and also increasing VD and LC status is a possible therapeutic approach that might aid patients with diabetes. Future clinical trials are needed to investigate whether VD and LC co-supplementation can successfully downregulate mTOR and can be used as adjuvant therapy in patients with diabetes.