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Introduction: The study sought to investigate the effect of weight change on hepatic steatosis (HS) incidence with or without liver fibrosis in metabolically healthy overweight or obese individuals. Methods: A cohort of 14,779 metabolically healthy men and women who were overweight or obese (body mass index ≥23 kg/m 2) and free from HS and an intermediate or high probability of fibrosis at baseline were followed for a median of 5.2 years. Metabolic health was defined as freedom from the components of metabolic syndrome and a homeostatic model assessment of insulin resistance 5.0%, relative to the no weight change group (–0.9% to 0.9%) were 0.52 (0.44–0.60), 0.83 (0.75–0.92), 1.21 (1.10–1.33), and 1.51 (1.36–1.69), respectively. Clinically relevant weight loss of >5% was also associated with a lowered risk of HS with intermediate or high probability of advanced fibrosis. In mediation analyses, associations remained significant, although adjustment for metabolic risk factors was attenuating. Discussion: Clinically relevant weight loss was associated with a reduced risk of developing nonalcoholic fatty liver disease with or without intermediate or high probability of advanced fibrosis in metabolically healthy overweight or obese individuals.

OBJECTIVES Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-Reactive Protein (CRP) are markers of inflammation that are elevated in bipolar disorder (BD) and are also related to a higher risk of metabolic syndrome (MetS). This study aimed at investigating for the first time the association between NLR, PLR, and CRP and the metabolic status in BD. METHODS We assessed the association between biomarkers and the metabolic status: number of metabolic risk factors, presence of MetS, insulin sensitivity (Quantitative Insulin Sensitivity Check Index, QUICKI) and insulin resistance (Homeostatic Model Assessment for Insulin Resistance, HOMA-IR index), in a sample of 219 outpatients with BD. RESULTS 25.9% of the sample met the criteria for MetS. High levels of CRP were found in 12% of the sample. Older age, low PLR, high NLR, and high CRP levels significantly predicted a higher number of MetS risk factors (p

Background and purpose: Insulin resistance (IR) can negatively affect clinical outcomes in acute ischemic stroke (IS) patients. Safe and cost-saving interventions are still needed to improve glycemic indices in this population. The primary objective was to evaluate L-carnitine (LC) effects in acute IS patients’ homeostatic model assessment of IR (HOMA-IR). Experimental approach: In this randomized, double-blind placebo-controlled clinical trial, critically ill IS patients were allocated to receive daily oral L-carnitine (1.5 g) or a placebo for six days. Fasting serum levels of glucose, insulin, C-reactive protein, LC, and HOMA-IR were measured on days 1 and 7. Mechanical ventilation duration, ICU/hospital duration, illness severity score, sepsis, and death events were assessed. Findings/Results: Forty-eight patients were allocated to the research groups, 24 patients in each group, and all were included in the final analysis. LC administration showed a decrease in mean difference of HOMA-IR and insulin levels at day 7 compared to placebo, -0.94 ± 1.92 vs 0.87 ± 2.24 (P = 0.01) and -2.26 ± 6.81 vs 0.88 ± 4.95 (P = 0.03), respectively. However, LC administration did not result in significant improvement in clinical outcomes compared to placebo. The short duration of intervention and low sample size limited our results. Conclusion and implication: Supplementation of L-carnitine improved HOMA-IR index in acute IS patients admitted to the critical care unit. Supplementation of LC would be a potential option to help to control IR in critically ill acute IS patients.

Renal allograft is vulnerable to numerous insults and is associated with metabolic derangements. Macrophages are regulators of inflammation and play a role in obesity, lipid metabolism and insulin resistance (IR). The present study was designed to assess macrophage activation, reflected by serum soluble CD163 (sCD163), in renal transplant recipients (RTR) and its relation to chronic allograft dysfunction (CAD) and metabolic derangements.Fifty recipients of renal transplantation (RT) [22 with stable renal function and 28 with CAD] and 20 age- and sex-matched healthy controls were enrolled in the study. Serum sCD163 and high sensitivity C-reactive protein (hsCRP) were measured using enzyme-linked immunosorbent assay. Anthropometric measurements, renal function, lipid profile and homeostatic model assessment of IR (HOMA-IR) were estimated. Renal interstitial fibrosis (IF) was graded in renal biopsies of CAD.RTR mean age was 38.84 ± 9.28 years and 83% of them were males. Post-transplant dyslipidemia, diabetes and IR (HOMA-IR2) were present in 42%, 24% and 86% of RTR respectively. Serum sCD163 levels were significantly higher in RTR with stable renal function and CAD than in healthy controls (814.41 ± 59.62 ng/ml and 1021.21 ± 120.82 ng/ml vs. 602.90 ± 114.98 ng/ml respectively) and in RTR with CAD than in patients with stable renal function (p 0.001). Serum sCD163 levels were positively correlated with body mass index, waist-to-hip ratio, worsening renal function, dyslipidemia, HOMA-IR and serum hsCRP in RTR and with the degree of renal IF in RTR with CAD (p 0.05). ROC curve showed that serum sCD163 was superior to serum hsCRP in detecting CAD after RT (AUC = 0.972 vs. 0.753 respectively, p = 0.001).Macrophage activation, reflected by increased circulating sCD163, may play a role in the development of CAD and metabolic derangements after RT. Serum sCD163 could be a potential biomarker for renal allograft dysfunction.

Objectives This study aimed to determine the safety and efficacy of canagliflozin in comparison to metformin in polycystic ovary syndrome (PCOS) patients with insulin resistance (IR). Methods A single center, prospective, randomized open-label (ratio 1:1) non-inferiority trial was conducted at the Department of Endocrinology, Shanghai Tenth People's Hospital, between July 2019 and April 2021. Women aged 18-45 years with PCOS and IR were enrolled and randomly assigned to either 100 mg (n = 33) canagliflozin daily or 1500-2000 mg metformin daily (n = 35) for 12 weeks. The primary outcome was changes in homeostatic model assessment (HOMA)-IR after 12 weeks of treatment. The secondary outcomes included changes in anthropometric measurements, menstrual frequency, sex hormone levels, metabolic parameters, and body fat distribution. Results For lowering of HOMA-IR after 12 weeks of treatment, canagliflozin was found to be non-inferior to metformin (least-squares mean difference -0.81% [95% CI: -2.13 to 0.51]). Both canagliflozin and metformin could significantly improve menstrual pattern, reduce body weight and total fat mass, and decrease triglyceride levels. Compared with metformin, canagliflozin had significant advantages in reducing uric acid and dehydroepiandrosterone sulfate levels. Pruritus vulvae (9.09%) and gastrointestinal reaction (55.55%) were the main adverse events in the metformin group and canagliflozin group, respectively. Conclusion Our study demonstrates that canagliflozin was not inferior to metformin in PCOS patients with IR, which suggests that sodium-glucose co-transporter 2 inhibitors should be considered as effective drugs in the treatment of PCOS patients with IR. This article is protected by copyright. All rights reserved.

Background: The emergence of isolated high blood pressure (HBP) among adolescents and its relation to obesity needs to be investigated. Aim: This study aims to assess prevalence, underlying risk factors, and consequences of HBP among adolescents in Egypt. Methods: We consolidated findings from three studies. The first one examined 150 adolescents (age: 16–18 years) for HBP and obesity using body mass index (BMI); the second one studied 150 adolescents for the lifestyle risk factors in relation to depression, anxiety, general health score, and suicidal score (SS) using relevant tools; the third one was a nested case–control study of 60 obese versus 60 non-obese adolescents examined for HBP, BMI, lifestyles and dietary habits, biochemical markers as lipid profile, fasting blood sugar (FBS), insulin, and homeostatic model assessment for insulin resistance (HOMA-IR). Results: In Stage I, the prevalence of HBP was 8% of whom, 58.3% were obese. Stage II: Dietary risk behavior as junk foods (high in salt) and soft drinks was 75.3% and 80%, respectively, and was linked with a high SS. Smoking was associated with a high anxiety score (p

Evidence shows that genetic polymorphisms in perilipin 1 gene (PLIN1) are associated with excessive accumulation of body fat and disturbances in cardiometabolic markers. Therefore, the aim of this study was to verify whether the SNP PLIN1 11482 G>A (rs894160) interacts with nutrient intake, anthropometric, body composition and cardiometabolic markers in adults with normal-weight obesity (NWO) syndrome. A cross-sectional study was carried out with 116 individuals aged 20–59 years, with normal BMI and high percentage of body fat. Anthropometric and body composition measures, glycaemic control and serum lipid markers, SNP PLIN1 11482 G>A and nutrient intake were evaluated. Interactions between nutrient intake and the SNP were determined by regression models and adjusted for potential confounders. The SNP frequency was 56·0 % GG, 38·8 % GA and 5·2 % AA. Anthropometric measures and biochemical markers were not different according to genotype, except for total cholesterol (TC), LDL-cholesterol and non-HDL-cholesterol concentrations. However, important interactions between the SNP and dietary intake were observed. Carbohydrate intake interacted with the SNP PLIN1 11482 G>A to modulate waist circumference (WC) and the homeostatic model assessment of insulin resistance index. Interaction of lipid intake and the SNP modulated TC and LDL-cholesterol concentrations, and the interaction between protein intake and the SNP tended to modulate weight, WC and BMI. The SNP PLIN1 11482 G>A seems to modulate responses in anthropometric and lipid profile biomarkers of subjects with NWO depending on the dietary macronutrient composition, which may have long-term impact on cardiometabolic markers.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. Insulin resistance and dyslipidemia are linked to PCOS. l-Carnitine supplementation as a management strategy for women with PCOS has been proposed. The effect of l-carnitine supplementation on insulin resistance, sex hormone-binding globulin (SHBG) and lipid profile in overweight/obese women with PCOS was investigated. This randomized, double-blind, controlled clinical trial, was conducted on 62overweight/obese women with PCOS. Participants were randomly assigned into two groups to receive 1000 mg/day l-carnitine or placebo (1000 mg starch) for 12 weeks. l-Carnitine supplementation compared to the placebo showed a significant improvement in insulin [− 0.7 (− 7.3 to 4.0) vs. 0.7 (− 3.0 to 5.2); P = 0.001], homeostatic model assessment for insulin resistance [− 0.4 (− 1.7 to 1.1) vs. 0.0 (− 0.7 to 1.3); P = 0.002], quantitative insulin sensitivity check index (+ 0.01 ± 0.02 vs. − 0.01 ± 0.01; P = 0.02) and a non-significant change toward improvement in SHBG (+ 11.5 ± 40.2 vs. − 3.2 ± 40.2; P = 0.2). However, there was no significant differences between the two groups in serum levels of fasting plasma glucose, total cholesterol, triglyceride, low density lipoprotein-cholesterol and high density lipoprotein cholesterol (P > 0.05). 12-week l-carnitine supplementation in overweight or obese women with PCOS ameliorate insulin resistance, but has no effect on SHBG and lipid profile. Studies with higher dosages and duration of l-carnitine intake are required. The trial was registered on 30 December 2019 at Iranian Registry of Clinical Trials IRCT20191016045131N1. Registered on 30th December 2019 at Iranian Registry of Clinical Trials (IRCT20191016045131N1).

There is growing evidence that supplementation with carnosine, or its rate-limiting precursor β-alanine, can ameliorate aspects of metabolic dysregulation that occur in diabetes and its related conditions. The purpose of this systematic review and meta-analysis was to evaluate the effect of carnosine or β-alanine supplementation on markers of glycemic control and insulin resistance in humans and animals. We performed a systematic search of 6 electronic databases up to 31 December 2020. Primary outcomes were changes in 1) fasting glucose, 2) glycated hemoglobin (HbA1c), and 3) 2-h glucose following a glucose-tolerance test. A set of additional outcomes included fasting insulin and homeostatic model assessment of β-cell function (HOMA-β) and insulin resistance (HOMA-IR). We assessed risk of bias using the Cochrane risk of bias (RoB) 2.0 (human studies) and the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) RoB (animal studies) tools; and used the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach to assess certainty. We used Bayesian hierarchical random-effects models, with informative priors for human data and noninformative priors for animal data. Inferences were made on posterior samples generated by Hamiltonian Markov Chain Monte Carlo using 90% credible intervals (90% CrI) and calculated probabilities. Twenty studies (n = 4 human, n = 16 rodent) were included, providing data for 2 primary outcomes (fasting glucose and HbA1c) and 3 additional outcomes (fasting insulin, HOMA-β, and HOMA-IR). The model provides evidence that supplementation decreases fasting glucose [humans: mean difference (MD)0.5 = –0.95 mmol · L–1 (90% CrI: –2.1, 0.08); rodent: MD0.5 = –2.26 mmol · L–1 (90% CrI: –4.03, –0.44)], HbA1c [humans: MD0.5 = –0.91% (90% CrI: –1.46, –0.39); rodents: MD0.5 = –1.05% (90% CrI: –1.64, –0.52)], HOMA-IR [humans: standardized mean difference (SMD)0.5 = –0.41 (90% CrI: –0.82, –0.07); rodents: SMD0.5 = –0.63 (90% CrI: –1.98, 0.65)], and fasting insulin [humans: SMD0.5 = –0.41 (90% CrI: –0.77, –0.07)]. GRADE assessment showed our certainty in the effect estimate of each outcome to be moderate (human outcomes) or very low (rodent outcomes). Supplementation with carnosine or β-alanine may reduce fasting glucose, HbA1c, and HOMA-IR in humans and rodents, and fasting insulin in humans; both compounds show potential as therapeutics to improve glycemic control and insulin resistance. This review was registered at PROSPERO as CRD42020191588., Statement of Significance: This study includes all available human and animal data to provide the most comprehensive assessment to date of the effects of carnosine and β-alanine supplementation on glycemic control and insulin resistance.

Background Obesity is one of the most challenging clinical syndromes associated with deleterious health problems. Waist-to-height ratio (WHtR), a newer index for abdominal fat assessment, can be a superior tool in the evaluation of cardiometabolic risk. This study aimed to determine the relation between WHtR and lipid cardiovascular risk ratios and insulin resistance (IR) in children and adolescents with exogenous obesity. Results This analytical cross-sectional study included 80 children and adolescents with exogenous obesity, compared to 80 age- and sex-matched healthy non-overweight non-obese controls. Fasting lipid profile (total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL) and low-density lipoprotein (LDL)), fasting insulin, and fasting blood glucose were done and lipoprotein risk ratios were calculated; TC/HDL, LDL/HDL, non-HDL/HDL, and TG/HDL). In addition, homeostatic model assessment for IR (HOMA IR), triglyceride glucose index (TyG), TyG-BMI, and TyG-WC were calculated. The study group included 55 (34.4%) males and 105 (65.6%) females with a mean age of 13.6 ± 2.22 years. Obese group had significantly higher TC, TG, LDL, non-HDL, LDL/HDL, TC/HDL, non-HDL/HDL, and TG/HDL, with significantly lower HDL. In addition, they had significantly higher FBG, HOMA IR, TyG, TyG-BMI, and TyG-WC indices compared to the control group. There were statistically significant correlations between WHtR and lipid profile, lipid risk ratios and indices of IR. WHtR was found to be an independent predictor of IR by linear regression analysis. Conclusion WHtR can be an excellent, easy, and reliable clinical predictor for cardiovascular risk and IR in children and adolescents with exogenous obesity.

Shan-Shan Cui,1 Li-Jun Duan,1 Jun-Feng Li,1 Yong-Zhang Qin,2 Su-Qing Bao,1 Xia Jiang1 1Department of Endocrinology and Metabolism, Tianjin First Central Hospital, Tianjin, People’s Republic of China; 2Department of Endocrinology, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Shan-Shan CuiDepartment of Endocrinology and Metabolism, Tianjin First Central Hospital, No. 24 of Fukang Road, Nankai District, Tianjin, People’s Republic of ChinaTel +86 15022353629Email shanshan87@tom.comObjective: This study aims to explore the factors influencing the renal glucose threshold (RTG) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods: A cross-sectional study was conducted on 1009 hospitalized patients with T2DM using stratified random sampling. Blood glucose was monitored using a dynamic blood glucose monitor to obtain the mean blood glucose (MBG), which is used to calculate the RTG. The factors influencing the RTG were then analyzed.Results: The mean RTG in patients with newly diagnosed T2DM was 203.58 ± 55.22 mg/dl. The correlation between the RTG and the various variables was analyzed, and the results demonstrated that the RTG was correlated with the patient’s age (r = − 0.14539, P = 0.0001); MBG (r = − 0.35009, P = 0.0001); renal long neck (r = 0.16762, P = 0.0001); homeostatic model assessment for insulin resistance (r = − 0.38322, P = 0.0001); homeostatic model assessment for beta-cell function (r = − 0.22770, P = 0.0001); and the levels of glycated hemoglobin (HbA1c; r = 0.98994, P = 0.0001), blood urea nitrogen (r = − 0.11093, P = 0.0004), creatinine (r = − 0.26414, P = 0.0001), uric acid (r = − 0.20149, P = 0.0001), total cholesterol (r = 0.13192, P = 0.0001), low-density lipoprotein (r = 0.12466, P = 0.0001), thyroid-stimulating hormone (r = − 0.06346, P = 0.0460), beta-2 microglobulin (r = − 0.08884, P = 0.0056), and 24-hour urine glucose (r = 0.32115, P = 0.0001). Multiple linear stepwise regression analysis revealed that the HbA1c, 24-hour urine glucose, estimated glomerular filtration rate (eGFR), D-dimer, and body mass index (BMI) should be included in the final model, and HbA1c had the greatest impact on the RTG followed in descending order by the 24-hour urine glucose, eGFR, D-dimer, and BMI (P < 0.05).Conclusion: The RTG increases in most patients with newly diagnosed diabetes. The risk factors for the RTG are HbA1c, 24-hour urine glucose, eGFR, D-dimer, and BMI.Keywords: newly diagnosed, type 2 diabetes mellitus, renal glucose threshold, continuous glucose monitoring

Background: Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in children and its increasingprevalence is associated with a concomitant rise in obesity. Anthropometric measurements and non-invasive tests (liver function tests and USG abdomen) help in early recognition of non-alcoholic steatohepatitis (NASH) and reduce consequent morbidity and mortality. Aim: This study aims to study the occurrence of NASH in obese and overweight children and to derive the correlation of NASH with clinical and biochemical parameters in overweight and obese children. Methods: This hospital-based prospective study included children (age?18 years) who met the inclusion criteria. Diagnosis of NASH was based on the USG abdomen. Measurements included anthropometry, ultrasonography, fasting glucose, alanine aminotransferase (ALT), lipid profile and additional parameters of blood pressure, fasting insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). The variables were compared between children with and without NASH. Results: A total of 146 patients (female: 51.4%, male: 48.6%) were enrolled in the study. The most common age group affected was 11–18 years (50.7%) followed by 6–10 years (43.2%) and

We carried out a randomized, clinical trial in adults of both sexes with metabolic syndrome (MS) to assess the efficacy of high-intensity, low-volume interval training (HIIT) compared to moderate-intensity continuous training (MICT) on insulin resistance (IR), muscle mass, muscle activation, and serum musclin. Fasting glycemia, insulinemia, and glycated haemoglobin were determined by conventional methods, IR by Homeostatic model assessment (HOMA), lean mass by Dual-Energy X-ray Absorptiometry, muscle activation through carnosine by Proton Magnetic Resonance Spectroscopy, and musclin by Enzyme-Linked ImmunoSorbent Assay before and after a supervised, three-times/week, 12-week treadmill programme. HIIT (n = 29) consisted of six intervals with one-minute, high-intensity phases at 90% of peak oxygen consumption (VO2peak). MICT (n = 31) trained at 60% of VO2peak for 30 min. Patients had a mean age of 50.8 ± 6.0 years, body mass index of 30.6 ± 4.0 kg/m2, and VO2peak of 29.0 ± 6.3 mL.kg−1.min−1. Compared to MICT, HIIT was not superior at reducing Ln HOMA-IR (adjusted mean difference: 0.083 [95%CI − 0.092 to 0.257]), carnosine or musclin or at increasing thigh lean mass. HIIT increased carnosine by 0.66 mmol/kg.ww (95% CI 0.08–1.24) after intervention. Both interventions reduced IR, body fat percentage and increased total lean mass/height2 and VO2peak. Musclin showed a non-significant reduction with a small effect size after both interventions. Compared to MICT, HIIT is not superior at reducing IR, carnosine or musclin or at increasing skeletal muscle mass in adults with MS. Both training types improved IR, muscle mass and body composition. NCT03087721, March 22nd, 2017. NCT03087721. Registered March 22nd, 2017.

Polycystic ovary syndrome (PCOS) is generally considered a multifactorial disease caused by interactions between multiple susceptible genes and environmental factors. Glutamate cysteine ligase (GCL) is the rate-limiting enzyme in glutathione biosynthesis. This study examined the relationship between single nucleotide polymorphisms (SNPs) in the GCL catalytic subunit (GCLC C-129 T) and the modifier subunit (GCLM C-588 T) and PCOS. The two SNPs were genotyped in 1017 PCOS patients and 793 control women. Clinical, metabolic, hormonal, and oxidative stress parameters were also assessed. The frequencies of the CT + TT genotypes (21.6% vs. 27.7%) and T allele (11.5% vs. 14.7%) of SNP GCLC C-129 T were significantly lower in hyperandrogenism (HA)-PCOS patients than in control women. Logistic regression analysis revealed that the relative hazard of HA-PCOS was lower in individuals with the -129 T allele (CT + TT genotypes) than in those with the CC genotype (OR = 0.723, 95% CI: 0.571-0.915, P = 0.007). When using the GCLC-CC/GCLM-CC combined genotype as the reference category, the GCLC-CT + TT/GCLM-CC combined genotype was a protective factor for PCOS with HA (OR = 0.743, 95% CI: 0.566-0.976, P = 0.033). HA-PCOS patients with the -129 T allele had lower waist circumference, waist-to-hip ratio, and body mass index (BMI) and lower fasting insulin concentration and homeostatic model assessment of insulin resistance after correcting for age and BMI (P

Insulin resistance (IR) has been described in adults with systemic lupus erythematosus (SLE), though its mechanism has not been fully clarified. In this study, it was aimed to investigate insulin sensitivity for the first time in children with juvenile SLE (jSLE) by considering the effect of the already known contributing factors of IR.This is a cross-sectional study including 43 patients with jSLE and the same number of healthy controls matched for age, gender, pubertal stage, body mass index, and physical activity level. IR, as calculated by both homeostatic model assessment for insulin resistance (HOMA-IR) and a relatively new method, triglyceride glucose (TyG) index, was compared between the patients and their matched controls, also among the patients stratified by disease duration, corticosteroid use, and disease activity.Insulin resistance in the patient group was higher than the controls according to both HOMA-IR and TyG index (p 0.001 for both). In the patient group, no significant effect of disease duration, corticosteroid use, disease activity, and levels of anti-dsDNA, anti-cardiolipin IgM, anti-cardiolipin IgG, C3, and C4 on IR was demonstrated.Children with jSLE were found to have higher IR even after neutralizing the effects of the contributing factors which are expected to aggravate IR. This elevation in IR in jSLE seems not to be associated with corticosteroid use, disease duration, disease activity, or autoantibody levels. Thus, the presence of IR in jSLE cannot be explained solely with neither the already known contributing factors nor the increased inflammation of the disease. Key Points • In this study, insulin sensitivity was investigated for the first time in children with jSLE. • Children with jSLE have higher insulin resistance than healthy ones. • Insulin resistance in children with jSLE is independent of corticosteroid use, disease duration, disease activity or autoantibody, and complement levels.

Old age and insulin resistance accompanying metabolic syndrome are significant factors in the development of cardiovascular pathology.Aim. The aim of the study was to identify the age-related characteristics of developing insulin resistance on the body level and insulin resistance in rat adipocytes in animals with induced metabolic syndrome.Material and Methods. The study was carried out on male Wistar rats, which were divided into the following groups: group 1 (n = 14) comprised intact rats aged 150 days at the end of study; group 2 (n = 14) comprised rats aged 150 days at the end of 90-day period on diet with high contents of carbohydrates and fats (HCHFD); group 3 (n = 14) comprised intact rats aged 540 days at the end of the study; group 4 (n = 14) comprised rats aged 540 days after the end of 90-day HCHFD. Diet composition was as follows: 16% proteins, 21% fats, 46% carbohydrates including 17% fructose, 0.125% cholesterol, and replacement of drinking water with a 20%-fructose solution. At the end of the diet, body and organ weights were measured, and contents of glucose, insulin, triglycerides, serum leptin, and liver triglycerides were assessed. Epididymal adipose tissue adipocytes were isolated enzymatically. The content of reactive oxygen species (ROS) was investigated using 2,3-dihydrodichlorofluorescein diacetate. Increased ROS production and lipolysis inhibition in response to insulin were observed.Results. The signs of metabolic syndrome were observed in both age groups of HCHFD animals and included visceral obesity, hyperglycemia, and insulin resistance measured by homeostatic model assessment of insulin resistance (HOMA-IR). However, the obesity indicators were more pronounced in the group of young rats, whereas the signs of insulin resistance prevailed in older rats. Leptinemia directly correlated with HOMA-IR (rSp = 0.485, p = 0.03). Insulin resistance of adipocytes was observed in rats older than 540 days after the HCHFD.Conclusion. The obtained results suggested that age was a risk factor for the development of insulin resistance on the body level. Aging resulted in a decrease in the adipocyte sensitivity to insulin in metabolic syndrome. An increase in leptin may be a possible mechanism for worsening of insulin resistance with age.

Background: We studied whether musclin function in humans is related to glycemic control, body composition, and cardiorespiratory capacity.Methods: A cross-sectional study was performed in sedentary adults with or without metabolic syndrome (MS). Serum musclin was measured by enzyme-linked immunosorbent assay. Insulin resistance (IR) was evaluated by the homeostatic model assessment (HOMA-IR). Body composition was determined by dual-energy X-ray absorptiometry and muscle composition by measuring carnosine in the thigh, a surrogate of fiber types, through proton magnetic resonance spectroscopy. Cardiorespiratory capacity was assessed through direct ergospirometry.Results: The control (n=29) and MS (n=61) groups were comparable in age (51.5±6.5 years old vs. 50.7±6.1 years old), sex (72.4% vs. 70.5% women), total lean mass (58.5%±7.4% vs. 57.3%±6.8%), and peak oxygen consumption (VOpeak) (31.0±5.8 mL O2./kg.min vs. 29.2±6.3 mL O2/kg.min). Individuals with MS had higher body mass index (BMI) (30.6±4.0 kg/m2 vs. 27.4± 3.6 kg/m2), HOMA-IR (3.5 [95% confidence interval, CI, 2.9 to 4.6] vs. 1.7 [95% CI, 1.1 to 2.0]), and musclin (206.7 pg/mL [95% CI, 122.7 to 387.8] vs. 111.1 pg/mL [95% CI, 63.2 to 218.5]) values than controls (P˂0.05). Musclin showed a significant relationship with HOMA-IR (β=0.23; 95% CI, 0.12 to 0.33; P˂0.01), but not with VOpeak, in multiple linear regression models adjusted for age, sex, fat mass, lean mass, and physical activity. Musclin was significantly associated with insulin, glycemia, visceral fat, and regional muscle mass, but not with BMI, VCO2peak, maximum heart rate, maximum time of work, or carnosine.Conclusion: In humans, musclin positively correlates with insulinemia, IR, and a body composition profile with high visceral adiposity and lean mass, but low body fat percentage. Musclin is not related to BMI or cardiorespiratory capacity.

Objectives Insulin resistance may be associated with impaired lung function. The objective of this study was to examine the relationship between insulin resistance and lung function in asthmatic children. Methods We performed a cross-sectional study on asthmatic children aged 6–18 years at Tertiary Care Center, India. Fasting serum glucose and insulin levels were analyzed to calculate the homeostatic model assessment of insulin resistance (HOMA-IR) in 90 children. Lung function tests were performed. Spearman correlation was used to assess the relationship between insulin resistance and lung function. Linear regression was done to adjust the potential confounders. Results Insulin resistance was present in 15.5% of patients. We found a statistically significant inverse relationship between HOMA-IR and spirometric parameters such as forced expiratory volume in 1 s/forced vital capacity ratio and forced expiratory flow between 25 and 75% on Spearman correlation. However, adjusted regression for age, gender, and body mass index showed no significant association of lung function parameters with HOMA-IR. Conclusions Insulin resistance may be considered for the decline in lung function in asthmatic children.

Gemigliptin is one of the latest dipeptidyl peptidase-4 inhibitors developed by LG Life Sciences. Since the early 2000s, several randomized controlled trials (RCTs) of gemigliptin have been conducted. However, no study has directly compared its antidiabetic effects through a systematic review and meta-analysis. Therefore, in this study, we performed a systematic review and meta-analysis on RCTs. In particular, a subsequent meta-analysis was performed using Bayesian inference, and an updated quality management system model was integrated throughout our study. The mean differences and 95% confidence intervals for glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), homeostatic model assessment beta cell function (HOMA-β), and low-density lipoprotein (LDL) were evaluated for the efficacy outcomes of gemigliptin as compared to those of placebo and other oral antidiabetic drugs (OADs). In conclusion, we found that gemigliptin was superior to placebo and comparable to other OADs in terms of the effect on HbA1c, FPG, HOMA-β, and LDL. Further, gemigliptin was more effective than other OADs in HbA1c and HOMA-β in Bayesian inference analysis and statistically significant to other OADs in HbA1c and HOMA-β in sensitivity analysis excluding metformin. However, to confirm the results, more studies need to be analysed and the minimum clinically important difference must be applied.

This study aimed to evaluate the consumption of four types of analog rice made from different composite flours in alloxan-induced diabetic rats. Forty-two male Wistar rats were divided into seven groups and fed different food for six weeks: normal standard food (NSF), diabetic standard food (DSF), diabetic commercial rice (DCR), and diabetic analog rice (DAR) I∼IV. Total phenolic, dietary fiber, and resistant starch contents were evaluated in every analog and commercial type of rice. The parameters studied were fasting blood glucose, homeostatic model assessment (HOMA) insulin resistance (IR), HOMA β, lipid profile, atherogenic indexes (AI), weight changes, serum insulin and antioxidant activities. Total phenol, dietary fiber, and resistant starch were higher for analog rice IV than the other three analog rice. In addition, analog rice IV had a greater ability to lower fasting blood glucose, total cholesterol, triglycerides, and low-density lipoprotein levels. High density lipoprotein levels increased in all groups fed analog rice, and all diabetic rats fed four types of analog rice had improved weight, antioxidant activity, serum insulin levels, HOMA IR, HOMA β, and AI. Commercial rice consumption did not improve glucose or lipids profiles, antioxidant activity, serum insulin level, HOMA IR, HOMA β, or AI in diabetic mice. These results show that the four types of analog rice significantly improved serum markers in diabetic rats.

Objective: The pathogenesis of endometriosis has not been clearly explained. Inflammatory factors of ectopic implantation and the growth of ectopic endometrial cells have been subjects of major interest. The number of studies evaluating salusin-α and nesfatin-1 markers in patients with endometriosis is limited. No studies have evaluated the levels of anti-inflammatory markers for adropin and netrin-1 in patients with endometriosis. This study investigates how some important inflammatory regulatory markers in the inflammatory process affect the pathogenesis of endometriosis and determines whether any relationship exists between serum levels of these parameters and endometriosis and insulin resistance. Materials and methods: This prospective study included 73 patients with endometriosis diagnosed histopathologically after laparoscopic surgery and 75 healthy controls. Serum adropin, salusin-α, netrin-1, and nesfatin-1 levels and homeostatic model assessment of insulin resistance (HOMA-IR) values of the participants were measured. Results: The endometriosis group had significantly lower nesfatin-1 levels than the control group (3.0±0.53 vs 9.5±0.94, p=0.005). Between the patient and control groups, there was no difference regarding serum adropin, salusin-α, and netrin-1 levels (p=0.36, p=0.34, p=0.75, respectively). Nesfatin-1 had a significant positive correlation with adropin, salusin-α, and netrin-1 (r=0.563, p

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease. The beneficial effects of pomegranate have been shown on insulin resistance and obesity, which are linked to NAFLD pathogenesis. The aim of this study was to investigate the efficacy of pomegranate extract in patients with NAFLD. Forty-four NAFLD patients were randomly assigned to receive two pomegranate extract tablets or placebo for 12 weeks. Anthropometric measurements, serum lipids, glycemic indicators, and blood pressure were assessed at baseline and the end of the study. Pomegranate was associated with a reduction in the total cholesterol (p ˂ .001), triglyceride (p ˂ .001), low-density lipoprotein cholesterol (LDL-C)-to-high-density lipoprotein cholesterol (HDL-C) ratio (p ˂ .003), fasting blood sugar (p ˂ .001), homeostatic model assessment of insulin resistance (p = .02), diastolic blood pressure (p = .04), weight (p ˂ .001), body mass index (p ˂ .001), and waist circumference (p = .002), as compared to placebo. A significant increase was observed in serum HDL-C (p ˂ .001) after intervention with the pomegranate extract. However, no significant difference was shown between the two groups in serum insulin and LDL-C. The pomegranate extract supplement could be used as a complementary therapy along with existing therapies to improve glycemic indicators, serum lipids, anthropometric indices, and blood pressure in patients with nonalcoholic fatty liver.

Background. Non-alcoholic fatty liver disease (NAFLD) is a leading etiological factor of chronic liver diseases in children in industrialized countries. The high prevalence of small intestinal bacterial overgrowth (SIBO) is common in patients with NAFLD. Therefore, the purpose of our work is to study the impact of SIBO on the structural and functional parameters of the liver in obese/overweight children. Materials and methods. We examined 73 children aged 6 to 17 years, mean age of patients was (11.41 ± 2.68) years. Depending on the presence of overweight/obesity and the results of glucose hydrogen breath test (HBT), patients were divided into 2 groups: group 1 — 30 overweight/obese persons with SIBO, group 2 — 28 overweight/obese children without SIBO. The control group consisted of 15 apparently healthy children with normal weight and without SIBO. The presence of liver steatosis was established by means of transient elastography with controlled attenuation parameter. Additionally, we performed lactose HBT and a biochemical blood test with biochemical hepatogram, determination of lipid and carbohydrate parameters. Results. It was found that 70 % of children in group 1 had NAFLD, compared to 32 % in group 2. Also, erythrocyte sedimentation rate was higher in group 1 than in groups 2 and 3 (p, Актуальность. Неалкогольная жировая болезнь печени (НАЖБП) занимает лидирующие позиции среди хронических заболеваний печени у детей в промышленно развитых странах. Известно, что для пациентов с НАЖБП характерна высокая распространенность синдрома избыточного бактериального роста (СИБР). Цель работы — изучить влияние СИБР на структурно-функциональные показатели печени у детей с избыточным весом и ожирением. Материалы и методы. Обследовано 73 ребенка в возрасте от 6 до 17 лет, средний возраст пациентов составил (11,41 ± 2,68) года. В зависимости от наличия избыточного веса/ожирения и результатов водородного дыхательного теста (ВДТ) с глюкозой пациенты были разделены на 2 группы: 1 группа — 30 детей с избыточным весом/ожирением и наличием СИБР, 2 группа — 28 детей с избыточным весом/ожирением без СИБР. Контрольную группу составили 15 практически здоровых детей с нормальным весом и без СИБР по результатам ВДТ с глюкозой. Наличие стеатоза печени устанавливали при помощи транзиентной эластографии с функцией САР. Дополнительно проводили ВДТ с лактозой и биохимический анализ крови с определением показателей биохимической гепатограммы, липидного и углеводного спектров. Результаты. Установлено, что 70 % детей 1 группы имели сопутствующую НАЖБП по сравнению с 32 % во 2 группе. В 1 группе скорость оседания эритроцитов была выше, чем во 2 и 3 группах (p, Актуальність. Неалкогольна жирова хвороба печінки (НАЖХП) посiдає провідні позиції серед хронічних захворювань печінки в дітей у промислово розвинених країнах. Відомо, що для пацієнтів iз НАЖХП характерна висока поширеність синдрому надмірного бактеріального росту (СНБР). Метою роботи є вивчення впливу СНБР на структурно-функціональні показники печінки в дітей iз надмірною вагою та ожирінням. Матеріали та методи. Обстежено 73 дитини віком від 6 до 17 років, середній вік пацієнтів становив (11,41 ± 2,68) року. Залежно від наявності надмірної ваги/ожиріння i результатів водневого дихального тесту (ВДТ) з глюкозою пацієнти були розподілені на 2 групи: 1 група — 30 дітей iз надмірною вагою/ожирінням та СНБР, 2 група — 28 дітей iз надмірною вагою/ожирінням без СНБР. Контрольну групу становили 15 практично здорових дітей iз нормальною вагою та без СНБР за результатами ВДТ з глюкозою. Наявність стеатозу печінки встановлювали за допомогою транзієнтної еластографії з функцією САР. Додатково проводили ВДТ з лактозою та біохімічний аналіз крові з визначенням показників біохімічної гепатограми, ліпідного й вуглеводного спектрів. Результати. Встановлено, що в 70 % дітей 1 групи була супутня НАЖХП порівняно з 32 % у 2 групі. У 1 групі швидкість осідання еритроцитів була вищою, ніж у 2 і 3 групах (p

Background and aims We investigated the associations of 20-year body mass index (BMI) and waist circumference (WC) histories with risk of being 1) metabolically unhealthy overweight/obese (MUOO) vs metabolically healthy overweight/obese (MHOO) and 2) metabolically unhealthy normal weight (MUNW) vs metabolically healthy normal weight (MHNW). Methods and results Participants comprised 3018 adults (2280 males; 738 females) with BMI and WC measured, every ~5 years, in 1991–1994, 1997–1999, 2002–2004, 2007–2009, and 2012–2013. Mean age in 2012–2013 was 69.3 years, with a range of 59.7–82.2 years. Duration was defined as the number of times a person was overweight/obese (or centrally obese) across the 5 visits, severity as each person's mean BMI (or WC), and variability as the within-person standard deviation of BMI (or WC). At the 2013–2013 visit, participants were categorised based on their weight (overweight/obese or normal weight; body mass index (BMI) ≥25 kg/m2) and health status (healthy or unhealthy; two or more of hypertension, low high-density lipoprotein cholesterol, high triglycerides, high glucose, and high homeostatic model assessment of insulin resistance). Logistic regression was used to estimate associations with the risk of being MUNW (reference MHNW) and MUOO (reference MHOO) at the last visit. BMI and WC severity were each related to increased risk of being unhealthy, with estimates being stronger among normal weight than overweight/obese adults. The estimates for variability exposures became null upon adjustment for severity. Individuals who were overweight/obese at all 5 time points had a 1.60 (0.96–2.67) times higher risk of being MUOO than MHOO compared to those who were only overweight/obese at one (i.e., the last) time point. The corresponding estimate for central obesity was 4.20 (2.88–6.12). Greater duration was also related to higher risk of MUNW than MHNW. Conclusion Being overweight/obese yet healthy seems to be partially attributable to lower exposure to adiposity across 20 years of adulthood. The results highlight the importance of maintaining optimum and stable BMI and WC, both in adults who become and do not become overweight/obese.

Background Circadian rhythm is altered in individuals with obesity and insulin resistance, showing a smaller amplitude, less stability, and increased intradaily variation. Objective We compared reproducibility of circadian-rhythm parameters over time and under free-living vs. controlled conditions in participants with obesity and pre-diabetes after 2- and 3-year weight-loss maintenance during the 3-year PREVIEW (PREVention of diabetes through lifestyle intervention and population studies In Europe and around the World) study. Associations of obesity and insulin resistance with circadian-rhythm parameters were assessed. Subjects and methods Circadian-rhythm parameters were determined using continuous wrist-temperature measurements in free-living environments at year 2 (n = 24; age 56.8 +/- 10.3 y; body mass index (BMI) = 30 +/- 3.9 kg/m(2); homeostatic model assessment of insulin resistance (HOMA-IR) 2.4 +/- 1.1), at year 3 (n = 97; age 61.7 +/- 7.8; BMI = 29.7 +/- 3.9; HOMA-IR 2.9 +/- 2.1), and at year 3 in a controlled condition (n = 38; age 63.4 +/- 6.7; BMI = 28.7 +/- 3.9; HOMA-IR 3.8 +/- 1.4). Reproducibility was assessed by analyzing repeatability coefficients (CR), differences, and associations, over time as well as between conditions. Associations of BMI and HOMA-IR with circadian-rhythm parameters were assessed at y-3 in both conditions using factor analysis, followed by Pearson's correlations. Results Reproducibility of circadian-rhythm parameters over time in the free-living environments was high (CR 0.002-5.26; no significant differences; associated amplitudes r = 0.57; p < 0.01). In contrast, reproducibility between different conditions was low (CR 0.02-11.36; significant differences between most parameters (p < 0.05); yet associated amplitudes r = 0.59; p < 0.01). In the controlled vs. free-living condition circadian-rhythm was more stable; BMI and HOMA-IR were associated with the physiological amplitude-related parameters (r = -0.45; p < 0.01; r = -0.33; p < 0.05). In the free-living environment, BMI and behavioral circadian-rhythm parameters indicating circadian alignment, contributed most to the explained variation (47.1%), and were inversely associated (r = -0.22; p < 0.05), while HOMA-IR was inversely associated with stability-related circadian-rhythm parameters (r = -0.21; p < 0.05). Conclusions Circadian rhythm was highly reproducible over time in the free-living environments, yet different under different conditions, being more stable in the controlled condition. BMI may play a significant role in circadian alignment and vice versa in the free-living environment.

Alcohol consumption causes metabolic disorders and is a known risk factor for cardiovascular disease. However, some studies suggested that low level alcohol consumption improves insulin resistance. We evaluated the effects of alcohol consumption on insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR).This study included 280,194 people without diabetes who underwent comprehensive health examinations more than twice between 2011 and 2018. The levels of alcohol intake were obtained through a self-questionnaire. All subjects were divided into two groups based on the Korean standard cut-off value of HOMA-IR, 2.2. Cox proportional hazard analysis was used to assess the risk of insulin resistance according to alcohol consumption. The mean age of the study subjects was 38.2 years and 55.7% were men. During the follow-up period (median 4.13 years), HOMA-IR progressed from2.2 to ≥2.2 in 64,443 subjects (23.0%) and improved from ≥2.2 to2.2 in 21,673 subjects (7.7%). In the parametric survival analysis, alcohol consumption was associated with improvement of HOMA-IR (HR [95% CI], 1.09[1.03-1.14], 1.11[1.06-1.17] and 1.20[1.13-1.26], respectively). In the analysis classified according to changes in alcohol consumption amounts, increased alcohol consumption tended to prevent the progression of HOMA-IR (0.97[0.96-0.99]; p = 0.004). However, the association between the changes in alcohol consumption amounts and improvement of HOMA-IR was not statistically significant.This retrospective observational study has shown that alcohol consumption can improve insulin resistance and increased alcohol consumption amounts may have preventive effects on the progression of HOMA-IR compared to the baseline level.

Background : It is well established that obesity is a major health risk in diabetes and associated diseases. Epigenetic changes, specially DNA methylation, play an important role in regulation of adipokines. The objective of the present study was to evaluate the DNA methylation status at the promoter region of the leptin gene in obese individuals and its association with metabolic risk factors. Methods : The study included obese (n=100) and non-obese (n=75) individuals aged 25-45 years, and measured their physical, biochemical parameters (glucose, insulin, and lipid profiles) and leptin, DNA methyltransferase 1 (DNMT1), and DNA methyltransferase 3 beta (DNMT3b) mRNA expressions with real-time reverse transcription-polymerase chain reaction (qRT-PCR). DNA methylation of the leptin gene at the promoter region was analyzed by methyl-specific qPCR . Results : The study found that the DNA methylation level at the promoter area of the leptin gene was negatively associated with weight in obese subjects. Furthermore, study findings showed that the DNA methylation level was negatively associated with fasting insulin, glucose, homeostatic model assessment for insulin resistance, and total cholesterol. There was also a higher expression of DNMT1 and DNMT-3b in obese subjects as compared with non-obese subjects. Conclusion : The leptin epigenetic profile may be associated with obesity and its associated metabolic risk factors.

Background: Both intra-abdominal fat (IAF) and high-density lipoprotein cholesterol (HDL-C) are known to be associated with cardiometabolic health. We evaluated whether the accumulation of computed tomography (CT)-measured IAF over 5 years was related to baseline HDL-C concentration in a prospective cohort study.Methods: All participants were Japanese-Americans between the ages of 34 and 74 years. Plasma HDL-C concentration and CT measurements of IAF, abdominal subcutaneous fat (SCF), and thigh SCF cross-sectional areas were assessed at baseline and at 5-year follow-up visits.Results: A total of 397 subjects without diabetes were included. The mean±standard deviation HDL-C concentration was 51.6±13.0 mg/dL in men and 66.0±17.0 mg/dL in women, and the IAF was 91.9±48.4 cm2 in men and 63.1±39.5 cm2 in women. The baseline plasma concentration of HDL-C was inversely associated with the change in IAF over 5 years using multivariable regression analysis with adjustment for age, sex, family history of diabetes, weight change over 5 years, and baseline measurements of body mass index, IAF, abdominal SCF, abdominal circumference, thigh SCF, and homeostatic model assessment for insulin resistance.Conclusion: These results demonstrate that HDL-C concentration significantly predicts future accumulation of IAF over 5 years independent of age, sex, insulin sensitivity, and body composition in Japanese-American men and women without diabetes.

Urotensin-II (UII), a pluripotent vasoactive cyclic peptide, exhibits the progression of cardiovascular diseases and the glucose metabolic disorder of insulin resistance. Type 2 Diabetes Mellitus (T2DM) is entirely associated with insulin resistance. This study aimed to demonstrate the association of UII with insulin resistance in diabetic and non-diabetic subjects. A total of 73 male and female subjects aged 40-60 years were recruited in this case-control study. They included 35 non- diabetic subjects with a body mass index of (BMI) ≤ 25 and 38 patients with Diabetes Mellitus and BMI ≥ 25. UII levels were assessed beside other vasoactive and clinical parameters. The results revealed that patients with T2DM had elevated UII and Endothelin-I (ET-I) levels, along with positive correlations with the insulin-resistance marker of Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), blood pressure (BP), fasting blood glucose (FBG), hemoglobin A1c (HbA1C), and asymmetric dimethylarginine (ADMA). Results from stepwise multiple regressions indicated that UII correlated positively with the increases in the levels of serum cholesterol, ET-I, urea, ADMA, and FBG. This study concludes that the increase in UII level has a positive relation with insulin-resistance and the increase in ET-I level. However, UII could inhibit glucose-induced insulin secretion and, hence, can be utilized as a marker for T2DM and its complications through inflammatory microangiopathy.

Objectives Insulin resistance (IR) is a hallmark of type 2 diabetes mellitus (DM). The homeostatic model assessment of insulin resistance (HOMA-IR) provides an estimate for IR from fasting glucose and insulin serum concentrations. The aim of this study was to obtain a reference interval for HOMA-IR for a specific insulin immunoassay. Methods The Gutenberg Health Study (GHS) is a population-based, prospective, single-center cohort study in Germany with 15,030 participants aged 35–74 years. Fasting glucose, insulin, and C-peptide were available in 10,340 participants. HOMA-IR was calculated in this group and three reference subgroups with increasingly more stringent inclusion criteria. Age- and sex-dependent distributions of HOMA-IR and reference intervals were obtained. In a substudy three insulin assays were compared and HOMA-IR estimated for each assay. Results Among the 10,340 participants analyzed there were 6,590 non-diabetic, 2,901 prediabetic, and 849 diabetic individuals. Median (interquartile range [IQR]) HOMA-IR was 1.54 (1.13/2.19), 2.00 (1.39/2.99), and 4.00 (2.52/6.51), respectively. The most stringently selected reference group consisted of 1,065 persons. Median (IQR) HOMA-IR was 1.09 (0.85/1.42) with no significant difference between men and women. The 97.5th percentile was 2.35. There was a non-significant trend towards higher values with older age. Comparison of three immunoassays for insulin showed an unsatisfactory correlation among the assays and systematic differences in calculated HOMA-IR. Conclusions We present HOMA-IR reference intervals for adults derived by more or less stringent selection criteria for the reference cohort. In addition we show that assay specific reference intervals for HOMA-IR are required.