Occurrence Of Insulin Resistance Research Articles

Intermittent Energy Restriction for Adolescents With Obesity

Adolescent obesity requires effective and accessible treatment. Intensive dietary interventions have the potential to be used as adjunctive therapy for behavioral weight management. To examine the effectiveness of 2 diet therapies, delivered as part of an intensive behavioral weight management intervention, in adolescents with metabolic complications associated with obesity. This multisite, 52-week randomized clinical trial was conducted from January 31, 2018, to March 31, 2023, at 2 tertiary pediatric centers in Australia. Adolescents (aged 13-17 years) with obesity and 1 or more associated complications were included. Intensive behavioral interventions, delivered by a multidisciplinary team, comparing intermittent energy restriction (IER) or continuous energy restriction (CER), with 3 phases: very low-energy diet (weeks 0-4), intensive intervention (weeks 5-16), and continued intervention and/or maintenance (weeks 17-52). The primary outcome was body mass index (BMI) z score at 52 weeks in the IER vs CER group. Anthropometry, body composition, and cardiometabolic health were assessed at baseline and 52 weeks. The BMI z score and percentiles were determined using Centers for Disease Control and Prevention growth charts. Insulin resistance, dyslipidemia, and elevated hepatic function were assessed. A total of 141 adolescents (median [IQR] age, 14.8 [12.9-17.9] years; 71 male [50.4%]) were enrolled, 71 in the IER group and 70 in the CER group, and 97 (68.8%) completed the intervention, 43 in the IER group and 54 in the CER group. At week 52, both groups had reduced BMI z scores (estimated marginal mean change, -0.28 [95% CI, -0.37 to -0.20] for IER and -0.28 [95% CI, -0.36 to -0.20] for CER) and reduced BMI expressed as a percentage of the 95th percentile (estimated marginal mean change, -9.56 [95% CI, -12.36 to -6.83] for IER and -9.23 [95% CI, -11.82 to -6.64] for CER). No differences were found in body composition or cardiometabolic outcomes between the groups. Both groups had a reduction in the occurrence of insulin resistance (from 52 of 68 [76.5%] to 32 of 56 [57.1%] in the IER group and from 59 of 68 [86.8%] to 31 of 60 [57.1%] in the CER group) at week 16; however, at week 52, this effect was observed in the CER group only (from 59 of 68 [86.7%] to 30 of 49 [61.2%]). The occurrence of dyslipidemia was unchanged between baseline and week 52 (60 of 137 [42.6%] and 37 of 87 [42.5%], respectively), with a small improvement in occurrence of impaired hepatic function tests (37 of 139 [27.0%] and 15 of 87 [17.2%], respectively). No differences were found in dyslipidemia or hepatic function between groups. These findings suggest that for adolescents with obesity-associated complications, IER can be incorporated into a behavioral weight management program, providing an option in addition to CER and offering participants more choice. http://anzctr.org.au Identifier: ACTRN12617001630303.

Gingipain from Porphyromonas gingivalis causes insulin resistance by degrading insulin receptors through direct proteolytic effects

Periodontitis is a critical risk factor for the occurrence and development of diabetes. Porphyromonas gingivalis may participate in insulin resistance (IR) caused by periodontal inflammation, but the functional role and specific mechanisms of P. gingivalis in IR remain unclear. In the present study, clinical samples were analysed to determine the statistical correlation between P. gingivalis and IR occurrence. Through culturing of hepatocytes, myocytes, and adipocytes, and feeding mice P. gingivalis orally, the functional correlation between P. gingivalis and IR occurrence was further studied both in vitro and in vivo. Clinical data suggested that the amount of P. gingivalis isolated was correlated with the Homeostatic Model Assessment for IR score. In vitro studies suggested that coculture with P. gingivalis decreased glucose uptake and insulin receptor (INSR) protein expression in hepatocytes, myocytes, and adipocytes. Mice fed P. gingivalis tended to undergo IR. P. gingivalis was detectable in the liver, skeletal muscle, and adipose tissue of experimental mice. The distribution sites of gingipain coincided with the downregulation of INSR. Gingipain proteolysed the functional insulin-binding region of INSR. Coculture with P. gingivalis significantly decreased the INSR–insulin binding ability. Knocking out gingipain from P. gingivalis alleviated the negative effects of P. gingivalis on IR in vivo. Taken together, these findings indicate that distantly migrated P. gingivalis may directly proteolytically degrade INSR through gingipain, thereby leading to IR. The results provide a new strategy for preventing diabetes by targeting periodontal pathogens and provide new ideas for exploring novel mechanisms by which periodontal inflammation affects the systemic metabolic state.

Triglyceride-Glucose Index as A Crucial Marker for Polycystic Ovary Syndrome Women with Insulin Resistance

BACKGROUND: Insulin resistance (IR) is considered as the main driver of polycystic ovary syndrome (PCOS) pathogenesis. In PCOS condition, IR is frequently related to glucose, anthropometric profile, lipid profile, and hormone profile parameters. However, not all PCOS phenotype show IR. Therefore, this study was conducted to determine the association the parameters mentioned above in PCOS subjects with and without IR.METHODS: Fifty PCOS women with IR and 26 PCOS women without IR were recruited. All subjects underwent physical examination for measurement of weight, waist circumference (WC), and body mass index (BMI). Ferriman Gallwey Score (FGS) was used to evaluate hirsutism. Blood sample was taken from each subject for measurement of fasting glucose, postprandial glucose, fasting insulin, low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol, triglyceride (TG), sex hormone binding globulin (SHBG), thyroid-stimulating hormone (TSH), luteinizing hormone (LH), follicle stimulating hormone (FSH), and prolactin. Homeostatic model assessment for IR (HOMA-IR), TG-glucose index (TyGI), and free testosterone index (FTI) were then calculated.RESULTS: From all the parameters examined, only fasting insulin (p<0.001), HOMA-IR (p<0.001), SHBG (p=0.012), TG (p<0.001), and TyGI (p=0.008) that show significant differences between PCOS subjects with and without IR. After multivariate analysis, TyGI was found to have strong association with IR occurrence in PCOS subjects (p=0.005) with an odd ratio of 5.26 (1.65–16.74).CONCLUSION: TyGI appears to have a significant association with the IR occurrence in PCOS subjects. Hence, it can be suggested that TyGI could be an important marker for PCOS women with IR.KEYWORDS: insulin resistance, lipid metabolism, polycystic ovary syndrome, triglyceride-glucose index

Insulin resistance in NSCLC: unraveling the link between development, diagnosis, and treatment.

Lung cancer is responsible for the highest number of cancer-related deaths, with non-small cell lung cancer (NSCLC) being the most prevalent subtype. A critical aspect of managing lung cancer is reducing morbidity and mortality rates among NSCLC patients. Identifying high-risk factors for lung cancer and facilitating early diagnosis are invaluable in achieving this objective. Recent research has highlighted the association between insulin resistance and the development of NSCLC, further emphasizing its significance in the context of lung cancer. It has been discovered that improving insulin resistance can potentially inhibit the progression of lung cancer. Consequently, this paper aims to delve into the occurrence of insulin resistance, the mechanisms underlying its involvement in lung cancer development, as well as its potential value in predicting, assessing, and treating lung cancer.

The effect of the intestinal microbiota on the development of diabetes mellitus

The aim of the study was to identify the pathogenetic role of intestinal microflora in the development of diabetes mellitus. The review presents data on the peculiarities of the development of the intestinal microflora (MC), factors that determine the occurrence of dysbiosis, as well as the effect of dysbiotic changes in MC on the pathogenesis of various types of diabetes mellitus. The role of MC in the occurrence of insulin resistance, as well as the metabolism of peptides that determine eating behavior, has been studied. The contribution of short-chain fatty acids produced by microorganisms to the regulation of metabolism in diabetes mellitus is considered, and the role of pathogenicity factors of MC representatives is studied. Conclusion. The gut microbiota makes a significant contribution to the regulation of metabolism through various mechanisms. The resulting dysbiotic changes can negatively affect metabolic processes and be a risk factor for the development of diabetes mellitus. The identification of new pathogenetic pathways can be useful in finding points of application of drug therapy, which will contribute to improving the results of DM treatment.

Adipocyte-derived exosomal miR-22-3p modulated by circadian rhythm disruption regulates insulin sensitivity in skeletal muscle cells

Circadian rhythm disruption leads to dysregulation of lipid metabolism, which further drive the occurrence of insulin resistance (IR). Exosomes are natural carrier systems that advantageous for cell communication. In the present study, we aimed to explore whether and how the exosomal microRNAs (miRNAs) in circulation participate in modulating skeletal muscle IR induced by circadian rhythm disruption. In the present study, 24-h constant light (12-h light/12-h light, LL) was used to establish the mouse model of circadian rhythm disruption. Bmal1 interference was used to establish the cell model of circadian rhythm disruption. And in clinical experiments, we chose a relatively large group of rhythm disturbance-shift nurses. We showed that LL-induced circadian rhythm disruption led to increased body weight and visceral fat volume, as well as occurrence of IR invivo. Furthermore, exosomal miR-22-3p derived from adipocytes in the context of circadian rhythm disruption induced by Bmal1 interference could be uptaken by skeletal muscle cells to promote IR occurrence invitro. Moreover, miR-22-3p in circulation was positively correlated with the clinical IR-associated factors. Collectively, these data showed that exosomal miR-22-3p in circulation may act as potential biomarker and therapeutic target for skeletal muscle IR, contributing to the prevention of diabetes in the context of rhythm disturbance.

Content of adipokines and myokines in the blood of children and adolescents with obesity with polymorphism of the gene of liver triacylglycerol lipase rs2070895

BACKGROUND: A special role in the development of obesity is given to the genetic polymorphism of lipid metabolism enzymes, which include triacylglycerol lipase. However, there is still no information about the relationship between the single nucleotide polymorphism (snp) of the triacylglycerol lipase (LIPC) gene and the state of the endocrine function of mesenchymal tissues in childhood and adolescence obesity.AIM: The aim of the work was to study the relationship between snp LIPC for rs2070895 and changes in the content of adipokines, myokines, and the values of blood lipid metabolism in obese children and adolescents with different sexes.MATERIALS AND METHODS: In 96 healthy children and adolescents of different sexes and 98 obese peers, a study was conducted to assess the snp of the LIPC by rs2070895. In the blood serum of the examined, the content of total cholesterol, HDL cholesterol, LDL cholesterol, VLDL cholesterol, triacylglycerols, glucose, activity of alanine aminotransferase and aspartate aminotransferase, as well as the level of leptin, adiponectin, resistin, apelin, irisin, adipsin, myostatin, FGF21, osteocrine, oncostatin M , insulin and asprosin.RESULTS AND DISCUSSION: It has been established that obesity in boys is accompanied by hyperleptinemia, the occurrence of insulin resistance and disorders of blood lipid metabolism. In carriers of the heterozygous allele -250G/A, dyslipidemia and atherogenesis decrease in obesity, but alteration of internal organs increases. In girls with different LIPC genotypes for rs2070895, with obesity, there is an increase in the level of leptin and apelin, as well as irisin and insulin in the blood. In girls with the homozygous allele -250G/G, in addition to that, the content of resistin, asprosin and prolactin decreases in the blood, which is not are typical for girls with the heterozygous allele -250G/A. In obese girls with the heterozygous allele, the levels of adipsin, FGF-21, oncostatin M, and osteocrine increase, which are not typical for obese girls with the homozygous allele. Against the background of changes in the content of adipokines and myokines in girls homozygous for LIPC, obesity occurs dyslipemia, which is not typical for girls with the heterozygous allele -250G/A.CONCLUSION: The snp of LIPC at rs2070895 has sex-dependent effects on the levels of adipokines, myokines, and parameters lipid metabolism in the blood.

The Risk of Genetic Variants and Socioeconomic Lifestyle for Insulin Resistance Traits: A Mini-review

Insulin resistance is a complex metabolic characteristic that increases the risk of developing cardiovascular disease which results from hypertension and dyslipidemia. The interaction of hereditary and environmental are factors driving the emergence of such disorders. Molecular techniques have now enabled the discovery of uncommon variations linked to the etiology of these disorders. Lipid metabolism is connected to various genetic variations associated with the etiology of metabolic syndrome. There are several genetic variants including epigenetic modifications alongside immunological status interference with pathogenic infectious that are directly related to insulin resistance and glucose metabolism. However, functional studies are required to determine the role of various genetic variations and other distinct factors in the development of insulin resistance. This review aims to give a broad overview of the interference of these genetic variants in the occurrence of insulin resistance. We also provide a summary of current developments in the environmental and immune factors associated with type 2 diabetes.

Single-Nucleotide Polymorphisms in Base-Excision Repair-Related Genes Involved in the Risk of an Occurrence of Non-Alcoholic Fatty Liver Disease.

Oxidative stress is one of the pillars crucial in the development of a non-alcoholic fatty liver disease (NAFLD) and may cause DNA damage. Since the main pathway responsible for the repair of oxidative DNA damage is the base-excision repair (BER) pathway, we examined the relationship between the presence of different genetic variants of BER-associated genes and the risk of NAFLD. The study evaluates seven single nucleotide polymorphisms (SNPs) within five genes, hOGG1, APEX1, NEIL1, LIG3, LIG1, in 150 NAFLD patients and 340 healthy controls. The genotyping was performed using TaqMan probes and the results were presented as odds ratio with its corresponding 95% confidence interval. The following SNPs were assessed in the study: hOGG1 (rs1052133), APEX1 (rs176094 and rs1130409), NEIL1 (rs4462560), LIG3 (rs1052536), LIG3 (rs4796030), and LIG1 (rs20579). Four of the investigated SNPs, i.e., rs176094, rs1130409, rs4462560 and rs4796030, were found to be associated with NAFLD risk. Furthermore, the occurrence of insulin resistance in patients with steatosis depended on various LIG3 genetic variants. The findings imply the impact of genes involved in BER on NAFLD and fatty liver-related insulin sensitivity.

Gaining metabolic insight in older men undergoing androgen deprivation therapy for prostate cancer (the ADT & Metabolism Study): Protocol of a longitudinal, observational, cohort study.

Androgen deprivation therapy (ADT), a cornerstone of treatment for patients with locally advanced and metastatic prostate cancer, is associated with many adverse effects, including osteoporosis, sexual dysfunction, fatigue, and vasomotor symptoms. It is also associated with loss of muscle mass and increased adiposity. This change in body composition is likely the inciting event in the development of insulin resistance, an independent risk factor for diabetes mellitus and cardiovascular disease. Although the occurrence of insulin resistance during ADT has been reported, it remains unclear whether this insulin resistance is primarily hepatic or muscular. Similarly, the mechanisms that lead to insulin resistance also remain unknown. The ADT & Metabolism Study was designed to address these knowledge gaps, as the elucidation of the predominant site of insulin resistance will allow prevention strategies and the use of targeted, tissue-specific insulin-sensitizing agents in patients undergoing ADT. This prospective, mechanistic, single-center, 24-week, observational cohort study will enroll treatment-naïve adult men with prostate cancer about to undergo surgical or medical ADT for at least 24 weeks (ADT group; n = 50) and a control group of men who had undergone radical prostatectomy and are in remission (non-ADT group, n = 25). The primary outcome is to determine the site of insulin resistance (skeletal muscle or liver) using frequent sampling oral glucose tolerance test at baseline and 12 and 24 weeks after commencement of ADT (ADT group) or after enrollment in the study (non-ADT group). Secondary outcomes will assess changes in hepatic and intramyocellular fat (using magnetic resonance spectroscopy), inflammatory markers, adipokines, free fatty acids, and changes in body composition (assessed using dual-energy x-ray absorptiometry) and their correlation with the development of insulin resistance. Exploratory outcomes will include changes in muscle performance, physical function, physical activity, vitality, and sexual drive.

Correlation between Fructose Consumption Habits and Insulin Resistance with TyG Index Biomarkers Manifesting Metabolic Syndrome at the Elderly Monjok Integrated Services Post (Posyandu)

Aims: This study aims to prove the relationship between the habit of consuming food and/or drinks containing fructose and the occurrence of insulin resistance which manifests as metabolic syndrome in subjects at the Elderly Monjok Integrated Service Post (Posyandu), Mataram City, Indonesia.
 Study Design: Observational study with a cross-sectional design.
 Place and Duration of Study: Sample: Elderly Monjok Integrated Service Post (Posyandu), Mataram City, Indonesia from May to July 2022.
 Methodology: The study subjects were 48 people (10 men, 38 women, age range 45-90 years old). Fructose intake was collected using the 24 hours food recall method and assessed using the nutrisurvey software. Insulin Resistance is determined by the TyG Index method. Metabolic Syndrome is determined based on the parameter of the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III).
 Results: The study results showed that 52.1% of the subjects at the Elderly Monjok Integrated Service Post (Posyandu) Mataram city had insulin resistance and 62.5% had metabolic syndrome. The Chi-Square test showed that there was a significant relationship between fructose consumption habits and the occurrence of insulin resistance (ˆP=0.000) and metabolic syndrome (P=0.001).
 Conclusion: This study proves that there is a significant relationship between fructose consumption habits and the occurrence of insulin resistance which manifests as metabolic syndrome, on the subjects at the Elderly Monjok Integrated Service Post (Posyandu), Mataram City, Indonesia.

The relationship between vitamin D deficiency and insulin resistance during pregnancy

Background. Vitamin D insufficiency is associated with metabolic complications during pregnancy, including insulin resistance. Physiological processes during pregnancy contribute to increased insulin resistance, which, in turn, is the main symptom of gestational diabetes. There is evidence that excessive weight gain during pregnancy negatively affects the concentration of 25-hydroxyvitamin D (25(OH)D). The aim of the study was to determine the effect of vitamin D insufficiency and deficiency during pregnancy on the occurrence of insulin resistance in the third trimester against the background of excessive weight gain. Materials and methods. The prospective study included 65 pregnant women with a gestation period of up to 20 weeks (on average 17 weeks). At the initial stage, a survey (body weight before pregnancy), and a clinical examination were conducted. Subsequent examinations were carried out in the second (20 weeks) and third (28 weeks) trimesters. Weight gain during pregnancy was calculated as the difference in body weight (between the third and second trimester) divided by the number of gestational weeks in that interval, following the Institute of Medicine guidelines. Gestational weight gain was classified as excessive, taking into account pre-pregnancy body mass index. Predicting the probability of insulin resistance (according to the HOMA-IR) was assessed by the dynamics of body weight gain. Results. Median 25(OH)D in the second and third trimesters of pregnancy was 23 and 24 ng/ml, respectively. Vitamin D insufficiency (25(OH)D < 30 ng/ml) was observed in at least one of the trimesters in 47 (72.3%) pregnant women, while the permanent nature of vitamin D insufficiency was noted in 36 (55.4%) cases. Vitamin D deficiency was established in 8 (12.3%) pregnant women in the second trimester. Excessive weight gain during pregnancy was observed in 34 (52.3%) women. Insulin resistance was determined in 31 (47.7%) pregnant women in the third trimester. The median of immunoreactive insulin concentration and HOMA-IR was higher among women with vitamin D deficiency. Conclusion. Vitamin D insufficiency is associated with insulin resistance in the third trimester of pregnancy, which depends on excessive gestational weight gain.

Dietary Iron Unlikely to Cause Insulin Resistance in Horses.

Racehorses are often supplemented extra iron with the expectation that the iron will improve overall performance and health. A survey of 120 U.S. Thoroughbred trainers, representing 1978 Thoroughbreds from various regions of the U.S., was conducted to determine the average amount of dietary iron fed to Thoroughbred racehorses per day. Survey results indicated racehorses were fed an average of 3900 mg of iron per day from hay and grain alone. This exceeds the 0.8 mg/kg BW or 400 mg for a 500 kg working horse that the NRC 2007 recommends per day. Supplements increased the daily average intake of iron by an additional 500 mg Fe. Some equine nutritionists propose that excess dietary iron may be a causative factor in insulin resistance (IR). However, the occurrence of IR in Thoroughbred racehorses is very rare. This study did not find one confirmed veterinary diagnosis of IR in any of the surveyed trainers' Thoroughbred horses, whether racing, on a layoff, or retired. Given the iron content in these diets easily exceeds the NRC minimum daily requirements, it seems unlikely that dietary iron is an independent causative factor in IR.

Occurrence of Insulin Resistance with Recurrent Pregnancy Loss of Unknown Etiology in North Indian Hospital-based Women Population: A Pilot Study

Occurrence of Insulin Resistance with Recurrent Pregnancy Loss of Unknown Etiology in North Indian Hospital-based Women Population: A Pilot Study

The effect of non-alcoholic fatty liver disease on the functional state of the kidneys in patients with chronic heart failure

Aim: to study the functional state of the kidneys in patients with chronic heart failure (CHF) and non-alcoholic fatty liver disease (NAFLD).Materials and methods. 144 patients with CHF aged 45-70 years were divided into two groups: group 1 — persons with CHF and NAFLD, group 2 — CHF without NAFLD. A clinical examination was performed, the indices of FLI steatosis and NFS liver fibrosis were calculated, the functional state of the kidneys and the adipokine status were evaluated.Results. The main group of patients with CHF and NAFLD is mainly represented by people with grade I obesity (73 (84%) vs 5 (9%), p<0.05). Among patients with CHF and NAFLD, a clinically significant decrease in GFR<60 ml/min/1.73 m2 was significantly more often detected compared to patients with CHF without NAFLD (37% vs 21% in groups 1 and 2, respectively). The level of albuminuria was significantly higher in the group of patients with CHF and NAFLD (200.7±22.3 [54.7;390] vs 92.6±23.4 [10.2;188.7] mg/g in groups 1 and 2, respectively). The percentage of individuals with an AU/CR. urine ratio >30 mg/g was statistically significantly higher in group 1 compared to group 2 (82.1 vs 51.1% in groups 1 and 2, respectively). The level of serum leptin was significantly higher and the concentration of serum adiponectin was significantly lower compared to group 2 in the main group of patients with CHF and NAFLD compared to the control group. There was a significantly higher occurrence of insulin resistance in patients with CHF and NAFLD. Correlation analysis revealed the presence of statistically significant associations between the parameters characterizing the functional state of the kidneys and the indices of FLI, NFD, adipokines, and the severity of insulin resistance.Conclusion. In patients with CHF and NAFLD, a significant deterioration in the functional state of the kidneys was found, in comparison with patients with “isolated” CHF with comparable FC.

Fructose-Induced Insulin Resistance: Prospective Biochemical Mechanisms

Increased intake of dietary fructose is markedly associated with multiple negative health outcomes and burdens. Insulin resistance (IR) and type 2 diabetes mellitus (T2DM) are the most common complications that present with conjugated cellular-biochemical abnormalities. This article explains the involvement of increased dietary fructose intake in the occurrence of IR and T2DM and addresses basic metabolic mechanisms. PubMed, Medline, Science Direct, ADI, and WHO databases were searched through June 2021. Current research predicts that over 350 million people may have diabetes by 2030. IR acts as an influencer promoter of T2DM development. IR can occur as a result of high fructose intake. Fructose metabolism results in de novo lipogenesis, while its decreasing effect of peroxisome proliferator-activated receptor (PPAR) activity elevates the levels of inflammatory cytokines, resulting in down-regulation of insulin receptor substrate-1 phosphorylation. Fructose stimulates oxidative stress by activating nicotinamide adenine dinucleotide phosphate oxidase and synthesis of advanced glycation end-products. Fructose also stimulates purine-induced uric acid synthesis and leptin resistance, which contributes to abnormal insulin action. It is crucial to understand the mechanisms of fructose-induced IR via induction of oxidative stress, inflammation, leptin resistance, and uric acid production. This helps prevent and control variable diseases, T2DM being the most.

Insulin resistance and associated factors in female adolescents from two capital cities in the north and south of Brazil

BackgroundIt has been described that physiological changes in glucose metabolism, represented by insulin resistance (IR), are predicted during pubertal evolution, and obesity may be associated with its persistence even at the end of puberty. The aim of this study was to investigate the prevalence of IR in female adolescents with possible associated factors and evaluate the relationship of time since menarche (< 2 vs. ≥ 2 years) in the occurrence of IR in two Brazilian capital cities: Porto Velho (RO) and Porto Alegre (RS).MethodsThis is a cross-sectional school-based study, using information from the Study of Cardiovascular Risks (ERICA) database for adolescents aged 12–17 years, enrolled in public and private schools, in municipalities with more than 100,000 inhabitants in Brazil, between 2013 and 2014. The present study included 889 adolescents, 382 in Porto Velho (PVh) and 507 in Porto Alegre (PoA). The homeostasis model assessment for insulin resistance (HOMA-IR) ≥ 3.16 and fasting insulin ≥ 15 mU/L was used to determine the outcome variable of IR. Estimates of crude and adjusted prevalence ratios with confidence intervals of 95% were calculated using Poisson regression with robust variance. Sociodemographic, behavioral, reproductive and nutritional characteristics were considered as potential confounding factors in multivariable models based on a conceptual framework of IR determination.ResultsIn the total sample, the prevalence of IR was 22.03% (95% CI 17.84–26.89). After adjusting the models, age 15–17 years and time since menarche ≥ 2 years were found to act as protective factors for IR; in contrast, the highest probability of IR was observed in black adolescents, with increased waist circumference (WC) and overweight/obesity (Ow/Ob). The protective effect of two or more years since menarche (post-menarche) was observed for both higher HOMA-IR and fasting insulin in PVh; in PoA, such protection was maintained only for fasting insulin ≥ 15 mU/L after adjustments in the multivariate models.ConclusionsIR is more prevalent during the peri-menarche period, especially in younger and black adolescents, compared to their white and post-menarche counterparts. The association between Ow/Ob and high WC with the occurrence of IR was independent of age and ethnicity variables.

Insulin resistance in metabolic syndrome depending on the occurrence of its components.

Metabolic syndrome (MetS) is described as a cluster of several commonly occurring disorders including abdominal obesity, hypertension (HT) (≥ 130/85 mm Hg), carbohydrate disorders: impaired fasting glucose or type 2 diabetes mellitus and lipids disorders such as hypertriglyceridaemia (TG), and low levels of high-density-lipoprotein cholesterol (HDL-C). Insulin resistance (IR) is defined as a glucose homoeostasis disorder involving a decreased sensitivity of muscles, adipose tissue, liver, and other body tissues to insulin, despite its normal or increased concentration in blood. The study group included 424 subjects with MetS (260 females, 164 males). All patients were recruited for 24 months from the Internal Ward of the District Hospital in Wąbrzeźno, Poland and the Department of Endocrinology and Diabetology Collegium Medicum in Bydgoszcz, Poland. The diagnosis of the MetS was made on the basis of International Diabetes Federation (IDF) criteria. MetS diagnosis was established when three or more criteria were met. To evaluate and measure IR, a hyperinsulinaemic-euglycaemic clamp was performed in each patient. IR was also determined through HOMA-IR. All patients of the study group were diagnosed with obesity, 73.5% with high fasting glucose levels, 66.9% with HT, 48.3% with lower level of HDL-C, and 38.2% with TG. It did not have an influence on the IR results. The study group was divided into 6 subgroups according to the constellation of 3 particular components of MetS (O + DM2T + ↑TG; O + HT + DM2T; O + DM2T + ↓HDL-C; O + HT + IFG; O + HT + ↑TG and O + HT + ↓HDL-C). IR of different degree was diagnosed in all patients of the study group. The results of our study showed that the highest IR was observed in patients with central obesity accompanied by DM2T and ↑TG. Also in subgroups with DM2T and HT or DM2T and ↓HDL-C, a high index of IR was noticed. The occurrence of IR in patients with MetS is obvious. However, despite the fact that they are high or very high cardiovascular risk patients, they are not a homogeneous group. Such patients differ from each other depending on the presence and constellation of particular disorders that make up the diagnosis of the MetS. Patients with MetS are a heterogeneous group differing in degree of IR and the risk of CVD.

Co-Treatment with Cefotaxime and High-Fructose Diet Inducing Nonalcoholic Fatty Liver Disease and Gut Microbial Dysbiosis in Mice

High fructose diet causes metabolic syndrome and induces host gut microbial dysbiosis and related obesity and nonalcoholic fatty liver disease (NAFLD). Several antibiotic treatments could prevent fatty liver. However, there are studies that have demonstrated that a high-fructose diet could influence the gut microbial dysbiosis and induce fatty liver. The purpose of this study was performed to partially modify the gut bacterial composition with a single cefotaxime treatment, which might affect the fructose-induced NAFLD severity. The C57BL/6JNarl male mice were divided into four groups including vehicle/chow diet (VE-CD), vehicle/high-fructose diet (VE-FD), antibiotic (cefotaxime (CF))/CD, and CF/FD. The results showed that body weight gain, moderate hepatic steatosis severity, epididymal white adipose tissue hypertrophy, and insulin resistance occurrence with NAFLD-related symptoms were observed only in the CF-FD group. The raised protein expression of hepatic lipogenesis was observed in the CF-FD group, but lipolysis protein expression was no difference. The diversity and composition of microbiota were significantly reduced in the CF-FD group. The Erysipelatoclostridium, Enterobacteriaceae, Lachnospiraceae, and Escherichia Shigella were in increased abundance in the feces of CF-FD group compared with VE-FD group. The novel model reveals that particular antibiotics such as cefotaxime co-treatment with high-fructose diet may affect the gut microbiota accelerating the NAFLD and obesity.

In utero exposure to phenanthrene induced islet cell dysfunction in adult mice: Sex differences in the effects and potential causes

Epidemiological studies show that the burden of polycyclic aromatic hydrocarbons in human body is associated with the occurrence of insulin resistance and diabetes. In the present study, pregnant mice were exposed to phenanthrene (Phe) at doses of 0, 60 and 600 μg/kg body weight of by gavage once every 3 days. The female F1 mice at 120 days of age showed no change in their fasting glucose levels (FGLs) but exhibited significantly decreased homeostasis model assessment (HOMA) β-cell (49% and 43%) and significantly downregulated pancreatic proinsulin gene (ins2) transcription. The downregulation of transcription factors, such as PDX1, PAX4 and FGF21, indicated impaired development and function of β-cells. The significantly reduced α-cell mass in 60 and 600 μg/kg groups, and the significantly downregulated expression of proglucagon gene gcg and ARX in the 600 μg/kg group suggested that the development and function of α-cells had been impacted. The males exhibited significantly increased FGLs (1.14- and 1.15-fold) in Phe exposed treatments and significantly elevated HOMA β-cell (3.15-fold) in the 600 μg/kg group. Upregulated ins2 transcription and FGF21 protein in male mice prenatally exposed to 600 μg/kg Phe suggested that these animals appeared compensatory enhancement in β-cell function. The reduced serum estradiol levels and downregulated pancreatic estrogen receptor α and β were responsible for the dysfunction of β-cells in the females. In the males, the significantly elevated androgen levels in the 600 μg/kg group might be related to the upregulated ins2 transcription, and the increased expression of pancreatic FGF21 further demonstrated the enhancement of β-cell potential. The results will be helpful for assessing the risk of developing diabetes in adulthood after prenatal exposure to phenanthrene.