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Diabetes mellitus is a chronic metabolic disorder characterized by elevated blood glucose levels and has become the third leading threat to human health after cancer and cardiovascular disease. Recent studies have shown that autophagy is closely associated with diabetes. Under normal physiological conditions, autophagy promotes cellular homeostasis, reduces damage to healthy tissues and has bidirectional effects on regulating diabetes. However, under pathological conditions, unregulated autophagy activation leads to cell death and may contribute to the progression of diabetes. Therefore, restoring normal autophagy may be a key strategy to treat diabetes. High-mobility group box 1 protein (HMGB1) is a chromatin protein that is mainly present in the nucleus and can be actively secreted or passively released from necrotic, apoptotic, and inflammatory cells. HMGB1 can induce autophagy by activating various pathways. Studies have shown that HMGB1 plays an important role in insulin resistance and diabetes. In this review, we will introduce the biological and structural characteristics of HMGB1 and summarize the existing knowledge on the relationship between HMGB1, autophagy, diabetes, and diabetic complications. We will also summarize potential therapeutic strategies that may be useful for the prevention and treatment of diabetes and its complications. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) plays a crucial role in the development and progression of metabolism-related diseases such as diabetes, hypertension, tumors, and nonalcoholic fatty liver disease, and provides the basis for a common understanding of these chronic diseases. In this study, we provide a systematic review of the causes, mechanisms, and treatments of IR. The pathogenesis of IR depends on genetics, obesity, age, disease, and drug effects. Mechanistically, any factor leading to abnormalities in the insulin signaling pathway leads to the development of IR in the host, including insulin receptor abnormalities, disturbances in the internal environment (regarding inflammation, hypoxia, lipotoxicity, and immunity), metabolic function of the liver and organelles, and other abnormalities. The available therapeutic strategies for IR are mainly exercise and dietary habit improvement, and chemotherapy based on biguanides and glucagon-like peptide-1, and traditional Chinese medicine treatments (e.g., herbs and acupuncture) can also be helpful. Based on the current understanding of IR mechanisms, there are still some vacancies to follow up and consider, and there is also a need to define more precise biomarkers for different chronic diseases and lifestyle interventions, and to explore natural or synthetic drugs targeting IR treatment. This could enable the treatment of patients with multiple combined metabolic diseases, with the aim of treating the disease holistically to reduce healthcare expenditures and to improve the quality of life of patients to some extent. [ABSTRACT FROM AUTHOR]

Introduction: Skeletal muscle insulin resistance (IR) plays an important role in the pathogenesis of type 2 diabetes mellitus. Skeletal muscle is a heterogeneous tissue composed of different muscle fiber types that contribute distinctly to IR development. Glucose transport shows more protection in slow-twitch muscles than in fast-twitch muscles during IR development, while the mechanisms involved remain unclear. Therefore, we investigated the role of the mitochondrial unfolded protein response (UPRmt) in the distinct resistance of two types of muscle in IR. Methods: Male Wistar rats were divided into high-fat diet (HFD) feeding and control groups. We measured glucose transport, mitochondrial respiration, UPRmt and histone methylation modification of UPRmt-related proteins to examine the UPRmt in the slow fiber-enriched soleus (Sol) and fast fiberenriched tibialis anterior (TA) under HFD conditions. Results: Our results indicate that 18 weeks of HFD can cause systemic IR, while the disturbance of Glut4-dependent glucose transport only occurred in fasttwitch muscle. The expression levels of UPRmt markers, including ATF5, HSP60 and ClpP, and the UPRmt-related mitokine MOTS-c were significantly higher in slow-twitch muscle than in fast-twitch muscle under HFD conditions. Mitochondrial respiratory function is maintained only in slow-twitch muscle. Additionally, in the Sol, histone methylation at the ATF5 promoter region was significantly higher than that in the TA after HFD feeding. Conclusion: The expression of proteins involved in glucose transport in slowtwitch muscle remains almost unaltered after HFD intervention, whereas a significant decline of these proteins was observed in fast-twitch muscle. Specific activation of the UPRmt in slow-twitch muscle, accompanied by higher mitochondrial respiratory function and MOTS-c expression, may contribute to the higher resistance to HFD in slow-twitch muscle. Notably, the different histone modifications of UPRmt regulators may underlie the specific activation of the UPRmt in different muscle types. However, future work applying genetic or pharmacological approaches should further uncover the relationship between the UPRmt and insulin resistance. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine disorder in women of reproductive age. Its clinical characteristics are mainly oligo-ovulation or anovulation, hyperandrogenemia (HA) and insulin resistance (IR). PCOS is considered to be one of the main causes of infertility in women of childbearing age, and its pathogenesis is still unclear. Intestinal flora, known as the "second genome" of human beings, is closely related to metabolic diseases, immune diseases and infectious diseases. At the same time, mounting evidence suggests that intestinal flora can regulate insulin synthesis and secretion, affect androgen metabolism and follicular development, and is involved in the occurrence of chronic inflammation and obesity. The imbalance of intestinal flora is caused by the abnormal interaction between intestinal flora and host cells caused by the change of intestinal microbial diversity, which is related to the occurrence and development of PCOS. The adjustment of intestinal flora may be a potential direction for the treatment of PCOS. [ABSTRACT FROM AUTHOR]

Hyperglycemia, which can be caused by either an insulin deficit and/or insulin resistance, is the main symptom of Type 2 diabetes, a significant endocrine metabolic illness. Conventional medications, including insulin and oral antidiabetic medicines, can alleviate the signs of diabetes but cannot restore insulin release in a physiologically normal amount. The liver detects and reacts to shifts in the nutritional condition that occur under a wide variety of metabolic situations, making it an essential organ for maintaining energy homeostasis. It also performs a crucial function in glucolipid metabolism through the secretion of hepatokines. Emerging research shows that feeding induces hepatokines release, which regulates glucose and lipid metabolism. Notably, these feedinginduced hepatokines act on multiple organs to regulate glucolipotoxicity and thus influence the development of T2DM. In this review, we focus on describing how feeding-induced cross-talk between hepatokines, including Adropin, Manf, Leap2 and Pcsk9, and metabolic organs (e.g.brain, heart, pancreas, and adipose tissue) affects metabolic disorders, thus revealing a novel approach for both controlling and managing of Type 2 diabetes as a promising medication. [ABSTRACT FROM AUTHOR]

Introduction: Aim of the present study was to evaluate the real-world impact of once-weekly (OW) subcutaneous semaglutide on different end-points indicative of metabolic control, cardiovascular risk factors, and beta-cell function in type 2 diabetes (T2D). Methods: This was a retrospective, observational study conducted in 5 diabetes clinics in Italy. Changes in HbA1c, fasting blood glucose (FBG), body weight, blood pressure, lipid profile, renal function, and beta-cell function (HOMA-B) during 12 months were evaluated. Results: Overall, 594 patients (97% GLP-1RA naïve) were identified (mean age 63.9 ± 9.5 years, 58.7% men, diabetes duration 11.4 ± 8.0 years). After 6 months of treatment with OW semaglutide, HbA1c levels were reduced by 0.90%, FBG by 26 mg/dl, and body weight by 3.43 kg. Systolic blood pressure, total and LDLcholesterol significantly improved. Benefits were sustained at 12 months. Renal safety was documented. HOMA-B increased from 40.2% to 57.8% after 6 months (p<0.0001). Discussion: The study highlighted benefits of semaglutide on metabolic control, multiple CV risk factors, and renal safety in the real-world. Semaglutide seems to be an advisable option for preservation of b-cell function and early evidence suggests it might have a role in modifying insulin resistance (HOMA-IR), the pathogenetic basis of prediabetes and T2D. [ABSTRACT FROM AUTHOR]

Pediatric obesity has become in the last forty years the most common metabolic disease in children and adolescents affecting about 25% of the pediatric population in the western world. As obesity worsens, a whole-body insulin resistance (IR) occurs. This phenomenon is more pronounced during adolescence, when youth experience a high degree of insulin resistance due the production of growth hormone. As IR progresses, the blunted control of insulin on adipose tissue lipolysis causes an increased flux of fatty acids with FFA deposition in ectopic tissues and organs such as the liver, leading to the development of NAFLD. In this brief review, we will discuss the clinical implications of IR and NAFLD in the context of pediatric obesity. We will review the pathogenesis and the link between these two entities, the major pathophysiologic underpinnings, including the role of genetics and metagenomics, how these two entities lead to the development of type 2 diabetes, and which are the therapeutic options for NAFLD in youth. [ABSTRACT FROM AUTHOR]

Background: Triglyceride glucose (TyG) index as a more convenient and reliable predictor of insulin resistance (IR) is thought to be associated with many diseases, but its relationship with cancer remains unclear. Methods: The meta-analysis was conducted to evaluate the effects of TyG index on cancer risk utilizing the available evidence. PubMed, EMBASE, Medline, Cochrane Library and Web of Science were searched from their inception up to July 2022. A random-effects model was used to calculate the effect estimates and 95% confidence intervals (CIs). Results: A total of 6 observational studies met our inclusion criteria, which including 992292 participants. The meta-analysis indicated that the higher TyG index increased cancer risk compared to the lower TyG index group (total effect size =1.14, 95% CI [1.08, 1.20], P<0.001). Conclusions: Our meta-analysis found that higher TyG index may increase the risk of cancer. More prospective cohort studies and basic research are warranted to verify the relationship. [ABSTRACT FROM AUTHOR]

Objective: To investigate how body fat influences glucose metabolism and hormone profiles in women with polycystic ovary syndrome (PCOS), compared to women without PCOS. Methods: We conducted a cross-sectional study of 166 women with PCOS and 139 age-matched control women at Peking University Third Hospital (Beijing, China) from March 2016 to December 2021. All participants underwent bioimpedance rate assessment of clinical, anthropometric, hormonal, and metabolic features. In particular, body composition parameters were assessed, based on the methods used in a previous study. Homeostasis model assessment-insulin resistance (HOMA-IR) and other indices calculated from fasting glucose and insulin were used to measure insulin resistance. The hormonal profiles [follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen (E2), prolactin (PRL), total testosterone (T), and androstenedione (A2)] were assessed by using biochemical methods. Two subgroup analyses were conducted according to waist-to-hip ratio (WHR; < 0.85, non-central obesity and ≥ 0.85, central obesity) and body fat percentage (BFP; < 35% for lean and ≥35% for obesity). The indices above were analyzed using a two-sided t-test or Wilcoxon rank sum test. Linear regression was used to investigate the effects of body composition on metabolism and sex hormones in the PCOS and control groups. Results: Compared to women without PCOS, women with PCOS and central obesity (P=0.021), PCOS and noncentral obesity (P<0.001), PCOS and high BFP (P<0.001), and PCOS and low BFP (P<0.001) had more severe glucose metabolism evaluated with HOMA-IR. Women with PCOS experienced greater insulin sensitivity impairment than did the normal population for every equal increase in BFP. LH, LH/FSH, total testosterone, and androstenedione were significantly higher in patients with PCOS than in healthy controls, regardless of WHR and BFP stratification. However, negative correlations existed between body fat indices (i.e., BFP and body mass index) and hormone indices (i.e., LH and androstenedione) in the PCOS group, but were absent in the control group. Conclusions: Obese and non-obese women with PCOS have more severe insulin resistance and sex-hormone disorders than women without PCOS. The effect of body fat on sex-hormone disorders is only exist in women with PCOS. These findings suggested that PCOS clinical guidelines should be more specific to body fat. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the relevance of metabolic syndrome (MetS) and metabolic scores to the occurrence, progression and prognosis of metastatic prostate cancer (mPCA), assessing the definition of the variables of metabolic syndrome, and the potential mechanisms of MetS and mPCA. Methods: Data were obtained from the database of prostate cancer follow-up at the Urology Centre of the First Affiliated Hospital of Xinjiang Medical University (N=1303). After screening by inclusion and exclusion criteria, clinical data of 190 patients diagnosed with mPCA by pathology and imaging from January 2010 to August 2021 were finally included, including 111 cases in the MetS group and 79 cases in the Non-MetS group. Results: The MetS group was higher than the Non-MetS group: T stage, Gleasson score, initial PSA, tumor load, PSA after 7 months of ADT (P<0.05), with a shorter time to progression to CRPC stage(P<0.05)[where the time to progression to CRPC was relatively shorter in the high metabolic score subgroup of the MetS group than in the low subgroup (P<0.05)].Median survival time was significantly shorter in the MetS group than in the NonMetS group (P<0.05),and there was a correlation with metabolic score, with the higher metabolic score subgroup having a lower survival time than the lower metabolic score subgroup (P<0.05). Conclusion: Those with mPCA combined with MetS had lower PSA remission rates, more aggressive tumors, shorter time to progression to CRPC and shorter median survival times than those with mPCA without MetS. Tumour progression and metabolic score showed a positive correlation, predicting that MetS may promote the progression of mPCA, suggesting that MetS may be a risk factor affecting the prognosis of mPCA. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a metabolic disorder resulting from impaired insulin secretion and resistance. Dipeptidyl peptidase (DPP)-IV is an enzyme known to trigger the catalysis of insulinotropic hormones, further abating the endogenous insulin levels and elevating the glucose levels in blood plasma. In the field of drug development, DPP-IV inhibitors have opened up numerous opportunities for leveraging this target to generate compounds as hypoglycemic agents by regulating incretin activity and subsequently decreasing blood glucose levels. However, the practice of synthetic drugs is an apparent choice but poses a great pharmacovigilance issue due to their incessant undesirable effects. The ideologywas set to inventively look upon different ethnomedicinal plants for their anti-diabetic properties to address these issues. To date, myriads of phytochemicals are characterized, eliciting an anti-diabetic response by targeting various enzymes and augmenting glucose homeostasis. Antioxidants have played a crucial role in alleviating the symptoms of diabetes by scavenging free radicals or treating the underlying causes of metabolic disorders and reducing free radical formation. PlantbasedDPP-IV inhibitors, including alkaloids, phenolic acid, flavonoids, quercetin, and coumarin, also possess antioxidant capabilities, providing anti-diabetic and antioxidative protection. This review article provides a new gateway for exploring the ability of plant-based DPP-IV inhibitors to withstand oxidative stress under pathological conditions related to diabetes and for reforming the strategic role of ethnomedicinal plants as potent DPP-IV inhibitors through the development of polyherbal formulations and nanophytomedicines to regulate incretin activity. [ABSTRACT FROM AUTHOR]

Objective: We aimed to investigate the short and long-term metabolic consequences of IGF1R systemic gene deficiency in mice. Methods: UBC-CreERT2, Igf1rfl/fl mutant mice were used to suppress IGF1R signaling in adult tissues by inducing postnatal generalized Igf1r deletion with tamoxifen. Animals were analyzed at two different ages: i) 13-weeks old young mice, and ii) 12-months old middle-aged mice. In addition, the effects of 10 weeks-long high-fat diet (HFD) were investigated in middle-aged mice. Results: Young IGF1R-deficient mice were insulin-resistant, with high IGF1, growth hormone (GH) and IGFBP3, as well as low IGFBP2 circulating levels. Males also presented increased triglycerides in liver. In contrast, middle-aged mice did not clearly show all of these alterations, suggesting possible compensatory effects. Middle-aged IGF1R-deficient male mice were able to counteract the negative effects induced by aging and HFD in adiposity, inflammation and glucose metabolism. A metabolic sexual dimorphism dependent on IGF1R was observed, especially in middle-aged mice. Conclusions: These results demonstrate that IGF1R is involved in metabolic homeostasis, with effects modulated by diet-induced obesity and aging in a sex dependent manner. Thus, IGF1R deficiency in mice is proposed as a useful tool to understand metabolic alterations observed in patients with IGF1R gene deletions. [ABSTRACT FROM AUTHOR]

Obesity is resulted from energy surplus and is characterized by abnormal adipose tissue accumulation and/or distribution. Adipokines secreted by different regional adipose tissue can induce changes in key proteins of the insulin signaling pathway in hepatocytes and result in impaired hepatic glucose metabolism. This study aimed to investigate whether exenatide affects key proteins of IRS2/PI3K/Akt2 signaling pathway in hepatocytes altered by the different regional fat depots. Six non-obese patients without endocrine diseases were selected as the research subjects. Their subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT)were co-cultured with HepG2 cells in the transwell chamber. In the presence or absence of exenatide, adipokines content in the supernatant of each experimental group was detected by ELISA. In addition, HepG2 cells in each co-culture group with and without insulin were collected, and the expression of key proteins IRS2, p-IRS2(S731), PI3K-p85, Akt2, and p-Akt2(S473) was detected by western blotting (WB). The results showed that the adipokines IL-8, MCP-1, VEGF, and sTNFR2 in the supernatant of HepG2 cells induced by different regional adipose tissue were significantly higher than those in the HepG2 group, and VAT released more adipokines than SAT. Furthermore, these adipokines were significantly inhibited by exenatide. Importantly, the different regional fat depot affects the IRS2/PI3K/Akt2 insulin signaling pathway of hepatocytes. Exenatide can up-regulate the expression of hepatocyte proteins IRS2, PI3K-p85, p-Akt2(S731) inhibited by adipose tissue, and down-regulate the expression of hepatocyte proteins p-IRS2(S731) promoted by adipose tissue. The effect of VAT on the expression of these key proteins in hepatocytes is more significant than that of SAT. But there was no statistical difference in the expression of Akt2 protein among each experimental group, suggesting that exenatide has no influence on the expression of Akt2 protein in hepatocytes. In conclusion, exenatide may improve hepatic insulin resistance (IR) by inhibiting adipokines and regulating the expression of key proteins in the IRS2/PI3K/Akt2 pathway. [ABSTRACT FROM AUTHOR]

Background and aims: The epidemiological characteristics of MAFLD and its relationship with atrial fibrillation (AF) are limited in China. Therefore, we explored the epidemiological characteristics of MAFLD from adults along with the association of MAFLD and 12-ECG diagnosed AF in a nationwide population from health check-up centers. Methods: This observational study used cross-sectional and longitudinal studies with 2,083,984 subjects from 2009 to 2017. Age-, sex-, and regionalstandardized prevalence of MAFLD was estimated. Latent class analysis (LCA) was used to identify subclusters of MAFLD. Multivariable logistic regression and mixed-effects Cox regression models were used to analyze the relationship between MAFLD and AF. Results: The prevalence of MAFLD increased from 22.75% to 35.58% during the study period, with higher rates in males and populations with high BMI or resided in northern regions. The MAFLD population was clustered into three classes with different metabolic features by LCA. Notably, a high proportion of MAFLD patients in all clusters had overweight and prediabetes or diabetes. The MAFLD was significantly associated with a higher risk of AF in the crosssectional study and in the longitudinal study. In addition, the coexistence of prediabetes or diabetes had the largest impact on subsequent AF. Conclusion: Our findings suggested a high prevalence of MAFLD and a high prevalence of other metabolic diseases in the MAFLD population, particularly overweight and glucose dysregulation. Moreover, MAFLD was associated with a significantly higher risk for existing and subsequent subclinical AF in the Chinese population. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) and obesity are two of the most challenging public health problems of our time. Therefore, understanding the molecular mechanisms that contribute to these complex metabolic disorders is essential. An underlying pathophysiological condition of T2D and obesity is insulin resistance (IR), a reduced biological response to insulin in peripheral tissues such as the liver, adipose tissue, and skeletal muscle. Many factors contribute to IR, including lifestyle variables such as a high-fat diet and physical inactivity, genetics, and impaired mitochondrial function. It is well established that impaired mitochondria structure and function occur in insulin-resistant skeletal muscle volunteers with T2D or obesity. Therefore, it could be hypothesized that the mitochondrial abnormalities are due to epigenetic regulation of mitochondrial and nuclear-encoded genes that code for mitochondrial structure and function. In this review, we describe the normal function and structure of mitochondria and highlight some of the key studies that demonstrate mitochondrial abnormalities in skeletal muscle of volunteers with T2D and obesity. Additionally, we describe epigenetic modifications in the context of IR and mitochondrial abnormalities, emphasizing mitochondria DNA (mtDNA) methylation, an emerging area of research. [ABSTRACT FROM AUTHOR]

Background: Exenatide is a GLP-1R agonist that often exhibits considerable interindividual variability in therapeutic efficacy. However, there is no evidence about the impact of genetic variants in the PPARD on the therapeutic efficacy of exenatide. This research was aimed to explore the influence of PPARD gene polymorphism on the therapeutic effect of exenatide, and to identify the potential mechanism futher. Methods: A total of 300 patients with T2DM and 200 control subjects were enrolled to identify PPARD rs2016520 and rs3777744 genotypes. A prospective clinical study was used to collect clinical indicators and peripheral blood of T2DM patients treated with exenatide monotherapy for 6 months. The SNaPshot method was used to identify PPARD rs2016520 and rs3777744 genotypes, and then we performed correlation analysis between PPARD gene variants and the efficacy of exenatide, and conducted multiple linear regression analysis of factors affecting the therapeutic effect of exenatide. HepG2 cells were incubated with exenatide in the absence or presence of a PPARd agonist or the siPPARd plasmid, after which the levels of GLP-1R and the ratio of glucose uptake were determined. Results: After 6 months exenatide monotherapy, we observed that homeostasis model assessment for insulin resistance (HOMA-IR) levels of the subjects with at least one C allele of the PPARD rs2016520 were significantly lower than those with the TT genotype, which suggested that the PPARD rs2016520 TT genotype conferred the poor exenatide response through a reduction of insulin resistance, as measured by HOMA-IR. The carriers of G alleles at rs3777744 exhibited higher levels of in waist to hip ratio (WHR), fasting plasma glucose (FPG), hemoglobin A1c (HbA1c) and HOMA-IR compared to individuals with the AA genotype following 6 months of exenatide treatment, potentially accounting for the lower failure rate of exenatide therapy among the AA homozygotes. In an insulin resistant HepG2 cell model, the PPARd agonists enhanced exenatide efficacy on insulin resistance, with the expression of GLP-1R being up-regulated markedly. Conclusion: These data suggest that the PPARD rs2016520 and rs3777744 polymorphisms are associated with exenatide monotherapy efficacy, due to the pivotal role of PPARd in regulating insulin resistance through affecting the expression of GLP-1R. This study was registered in the Chinese Clinical Trial Register (No. ChiCTR-CCC13003536). [ABSTRACT FROM AUTHOR]

Introduction: Research on the associations of physical activity and cardiorespiratory fitness with β-cell dysfunction and insulin resistance among adults in Sub-Saharan Africa (SSA) is limited. We assessed the association of physical activity and cardiorespiratory fitness with β-cell function, insulin resistance and diabetes among people living with HIV (PLWH) ART-naïve and HIV-uninfected Tanzanian adults. Method: In a cross-sectional study, we collected data on socio-demography, anthropometry, fat mass and fat free mass and C-reactive protein. Data on glucose and insulin collected during an oral glucose tolerance test were used to assess β-cell dysfunction (defined as insulinogenic index <0.71 (mU/L)/(mmol/L), HOMA-b index <38.3 (mU/L)/(mmol/L), and overall insulin release index <33.3 (mU/L)/(mmol/L)), oral disposition index <0.16 (mU/L)/(mg/dL) (mU/L)-1, insulin resistance (HOMA-IR index >1.9 (mU/L)/(mmol/L) and Matsuda index <7.2 (mU/L)/(mmol/L), prediabetes and diabetes which were the dependent variables. Physical activity energy expenditure (PAEE), sleeping heart rate (SHR), and maximum uptake of oxygen during exercise (VO2 max) were the independent variables and were assessed using a combined heart rate and accelerometer monitor. Logistic regressions were used to assess the associations. Results: Of 391 participants, 272 were PLWH and 119 HIV-uninfected. The mean age was 39 (± 10.5) years and 60% (n=235) were females. Compared to lower tertile, middle tertile of PAEE was associated with lower odds of abnormal insulinogenic index (OR=0.48, 95%CI: 0.27, 0.82). A 5 kj/kg/day increment of PAEE was associated with lower odds of abnormal HOMA-IR (OR=0.91, 95%CI: 0.84, 0.98), and reduced risk of pre-diabetes (RRR=0.98, 95%CI: 0.96, 0.99) and diabetes (RRR=0.92, 95%CI: 0.88, 0.96). An increment of 5 beats per min of SHR was associated with higher risk of diabetes (RRR=1.06, 95%CI: 1.01, 1.11). An increase of 5 mLO2/kg/min of VO2 max was associated with lower risk of pre-diabetes (RRR=0.91, 95%CI: 0.86, 0.97), but not diabetes. HIV status did not modify any of these associations (interaction, p>0.05). Conclusion: Among Tanzanian adults PLWH and HIV-uninfected individuals, low physical activity was associated with β-cell dysfunction, insulin resistance and diabetes. Research is needed to assess if physical activity interventions can improve β-cell function and insulin sensitivity to reduce risk of diabetes and delay progression of diabetes in SSA. [ABSTRACT FROM AUTHOR]

Background: Visceral obesity index (VAI) is an empirical mathematical model used to evaluate the distribution and function of fat. Some studies have shown that VAI may be associated with the development of insulin resistance. In view of the differences in insulin resistance among different ethnic groups, this study attempts to analyze the special relationship between VAI and insulin resistance in American adults. Methods: We conducted a cross-sectional study through NHANES database. A total of 27309 patients over the age of 18 from the United States took part in the survey. It was divided into two groups: the IR-positive group and the IR-negative group. The association of VAI with IR was evaluated by logistic regression analyses mainly, including univariate analysis, multivariate regression analysis, curve fitting analysis and subgroup analysis. Results: The results showed that in the full-adjusted model, there is a strong positive association between VAI level and insulin resistance (OR: 1.28 (1.2~1.37), P<0.001) and there is a threshold effect. Conclusions: This study suggests that higher VAI levels are associated with insulin resistance. VAI index may be used as a predictor of insulin resistance. [ABSTRACT FROM AUTHOR]

Objective: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduce glycaemia and weight and improve insulin resistance (IR) via different mechanisms. We aim to evaluate and compare the ability of GLP-1 RAs and SGLT-2 inhibitors to ameliorate the IR of nonalcoholic fatty liver disease (NAFLD) patients. Data Synthesis: Three electronic databases (Medline, Embase, PubMed) were searched from inception until March 2021. We selected randomized controlled trials comparing GLP-1 RAs and SGLT-2 inhibitors with control in adult NAFLD patients with or without T2DM. Network meta-analyses were performed using fixed and random effect models, and the mean difference (MD) with corresponding 95% confidence intervals (CI) were determined. The within-study risk of bias was assessed with the Cochrane collaborative risk assessment tool RoB. Results: 25 studies with 1595 patients were included in this network meta-analysis. Among them, there were 448 patients, in 6 studies, who were not comorbid with T2DM. Following a mean treatment duration of 28.86 weeks, compared with the control group, GLP-1 RAs decreased the HOMA-IR (MD [95%CI]; -1.573[-2.523 to -0.495]), visceral fat (-0.637[-0.992 to -0.284]), weight (-2.394[-4.625 to -0.164]), fasting blood sugar (-0.662[-1.377 to -0.021]) and triglyceride (- 0.610[-1.056 to -0.188]). On the basis of existing studies, SGLT-2 inhibitors showed no statistically significant improvement in the above indicators. Compared with SGLT-2 inhibitors, GLP-1 RAs decreased visceral fat (-0.560[-0.961 to -0.131]) and triglyceride (-0.607[-1.095 to -0.117]) significantly. Conclusions: GLP-1 RAs effectively improve IR in NAFLD, whereas SGLT-2 inhibitors show no apparent effect. [ABSTRACT FROM AUTHOR]

Objective: Obesity is characterized by a low-grade inflammatory state in adipose tissue. Tumor Necrosis Factor Weak Inducer of Apoptosis (TWEAK) and Cluster of Differentiation 163 (CD163) are cytokines potentially involved in the pathogenesis of obesity. Little is known about them in children. The aim of this study was to observe serum levels of TWEAK and CD163 in prepubertal children with obesity compared to lean, and to evaluate its changes after a 2-year intervention program in children with obesity. Methods: Case-control study with a prospective follow-up of cases for 2 years in a referral pediatric endocrine outpatient centre. Seventy-three prepubertal children with obesity, and forty-seven age- and gender-matched lean controls were studied. Sixty-two cases finished the program. Anthropometric parameters, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), lipid profile, and concentrations of TWEAK and CD163 were determined. Children with obesity were re-evaluated after a 2-year intervention program consisting of diet and exercise.Weight loss was considered if z-score Body Mass Index (BMI) decreased at least 0.5 Standard Deviations (SD). Results:We observed higher CD163 levels in children with obesity compared to controls. No significant differences were observed in TWEAK and CD163/TWEAK ratio at baseline. After the 2-year intervention program, TWEAK levels were higher and CD163/TWEAK ratio was lower in children with weight loss than those without weight loss. CD163 decreased in both groups. Conclusion: TWEAK and CD163 seem to have a role in the pathogenesis of obesity in prepubertal children. [ABSTRACT FROM AUTHOR]

The aim of this study is to explore the association between obstructive sleep apnea hypopnea syndrome (OSAHS) complicated with coronary heart disease (CHD) and inflammatory factors, glycolipid metabolism, obesity, and insulin resistance. A total of 400 patients diagnosed with OSAHS who underwent polysomnography (PSG) monitoring in the Sleep Diagnosis and Treatment Center of Beijing Luhe Hospital from March 2015 to September 2018 were selected and divided into the OSAHS group (n = 200) and the OSAHS + CHD group (n = 200) according to disease condition. The questionnaire survey was conducted, the somatology indexes were measured, and the PSG, insulin, glycolipid metabolism parameters, and serum inflammatory factors were detected. Body weight, body mass index, waist circumference, and Epworth sleepiness scale (ESS) score were all significantly increased in the OSAHS + CHD group compared with those in the OSAHS group (p < 0.05). The microarousal index (MAI), apnea hypopnea index (AHI), cumulative percentage of time spent at oxygen saturation below 90% (CT90%), oxygen desaturation index (ODI), lowest oxygen saturation (LSaO2), total apnea time (TAT), and mean oxygen saturation (MSaO2) had statistically significant differences between the OSAHS + CHD group and the OSAHS group (p < 0.05). According to the Spearman correlation analysis of AHI, LSaO2, MSaO2, CT90%, ODI, and MAI with HOMA-IR in both groups, MAI, AHI, CT90%, and ODI were positively correlated with HOMA-IR (r > 0), while LSaO2 and MSaO2 were negatively correlated with HOMA-IR (r < 0). Compared with the OSAHS group, the OSAHS + CHD group had an obviously increased level of triglyceride (TG) (p < 0.05), and obviously increased levels of serum inflammatory factors C-reactive protein (CRP), tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), and interferon-g (IFN-g) (p < 0.05). The occurrence of OSAHS complicated with CHD is related to inflammatory factors, glycolipid metabolism, obesity rate, and HOMA-IR. [ABSTRACT FROM AUTHOR]

Background: Glycine is a dietary non-essential amino acid that is low in obesity and increases following bariatric surgery. However, the exact mechanism responsible remains unclear and it is unknown whether hypoglycinemia is a cause or consequence of insulin resistance. Objective: Using multiple isotopically labeled tracers, we aimed to determine the underlying kinetic changes responsible for hypoglycinemia in obesity by: 1) Comparing glycine kinetics between participants with morbid obesity (BMI ≥ 32.5 kg/m2) to those with healthy weight (BMI < 25 kg/m2), and 2) Comparing glycine kinetic changes in participants with morbid obesity after bariatric surgery. Methods: [1,2-13C2] glycine, [2,3,3-2H3] serine, and [2H5] phenylalanine were infused to compare the glycine kinetic parameters between 21 participants with morbid obesity and 21 controls with healthy weight. Participants with morbid obesity then underwent bariatric surgery and 17 were re-studied 6 months later. Data were analyzed by non-parametric methods and presented as median (interquartile range). Results: Compared to controls, participants with morbid obesity had significantly lower plasma glycine concentrations at 163 (153-171) vs. 201 (172-227) µmol/L and significantly reduced de novo glycine synthesis rate at 86.2 (64.5-111) vs.124 (103-159) µmol·kg LBM-1·h1, p < 0.001. Following surgery, body weight and insulin resistance decreased and this was accompanied by significant increases in plasma glycine concentration to 210 (191-243) µmol/L as well as the de novo glycine synthesis rate to 127 (98.3-133) µmol·kg LBM-1·h-1, p < 0.001 vs. baseline. Conclusion: Hypoglycinemia in participants with morbid obesity was associated with impaired de novo glycine synthesis. The increase in plasma glycine concentration and de novo glycine synthesis plus the marked improvement in insulin resistance after bariatric surgery suggest that hypoglycinemia may be secondary to impaired glycine synthesis because of obesity-induced insulin resistance. Clinical Trial Registration: [ https://tinyurl.com/6wfj7yss ], identifier [NCT04660513]. [ABSTRACT FROM AUTHOR]

Adipose tissue, one type of loose connective tissue in the human body, maintains the primary task of energy storage. Adipose tissue is not only an energy reservoir but also plays a vital role as the largest endocrine organ of the whole body via releasing a variety of adipokines, which participate in many pathophysiological processes, such as energy metabolism regulation, glucose and lipid metabolism, and inflammation. Polycystic ovary syndrome (PCOS) is a disorder that mainly involves the female reproductive system, affecting women of childbearing age particularly. Insulin resistance (IR) and hyperandrogenemia (HA) have been implicated as a critical link involving the etiology and outcome of PCOS. A great deal of studies has bridged the gap between adipokines (such as Adiponectin, Chemerin, Metrnl, Apelin, Resistin, Visfatin, Leptin, Vaspin, Lipocalin 2, and Omentin) and reproductive fitness. In this review, we will focus on the adipokines' functions on PCOS and come up with some points of view on the basis of current research. [ABSTRACT FROM AUTHOR]

Background: While osteoporosis is characterized by skeletal fragility due to increased bone turnover and low bone mineral density (BMD), subjects with abdominal obesity and type-2 diabetes have increased risk of bone fractures despite low bone turnover and increased BMD. Diets with increased protein content are reported to increase bone turnover in healthy adults and may be a point of interest in preserving bone strength in subjects with abdominal obesity and/or type-2 diabetes. Methods: We examined the effect of 12-weeks dietary intervention on bone turnover in 64 adults with abdominal obesity using data from the MERITS trial. The trial was a randomized, controlled, double blinded study in which participants were allocated to receive either 60 g/d of whey protein hydrolysate or maltodextrin in combination with either high (30 g/d) or low dietary fiber intake (10 g/d). Primarily, we assessed changes in plasma markers of bone turnover Procollagen type 1 N-terminal propeptide (p1NP), C-terminal telopeptide type-1 collagen (CTX), and parathyroid hormone (PTH) within the four intervention groups. In addition, we measured u-calcium and u-carbamide excretion, 25(OH)D, and BMD by whole body DXA scans. Finally, we compared changes in insulin resistance (Homeostasis-model assessment of insulin resistance, HOMA-IR) with changes in bone turnover markers. The trial was registered at www.clinicaltrials.gov as NCT02931630. Results: Sixty-four subjects were included in the study. We did not find any effect of twelve weeks of high protein or high fiber intake on plasma levels of P1NP or CTX. There was a nonsignificant positive association between protein intake and PTH levels (p=0.06). U-calcium and u-carbamide increased in both protein groups. There was a positive association between change in HOMA-IR and PTH (p=0.042), while changes in P1NP and CTX did not associate to changes in HOMA-IR. Conclusion: Twelve weeks of increased whey protein intake in subjects with abdominal obesity did not affect markers of bone turnover significantly, although tended to increase PTH levels. Dietary fiber intake did not affect bone turnover. We report a positive association between change in HOMA-IR and PTH supporting a hypothesis of insulin resistance as a potential key factor in the expanding field of bone fragility in T2D subjects. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is an important variable in the diagnosis of metabolic syndrome (MetS). Currently, IR is not part of the existing pediatric definition of MetS, instead elevated fasting blood glucose (FBG) is measured as an indicator of hyperglycemia. Arguably, many obese children with severe IR are still able to regulate their FBG well. Hence, this study aimed to assess the utility of triglyceride-to-high-density lipoprotein cholesterol (TG : HDL-C) ratio as an IR marker in the modeling of pediatric MetS among children with obesity using structural equation modeling (SEM). A total of 524 blood samples from children with obesity (age 10–16 years old) were analyzed for FBG, lipids, insulin, leptin, and adiponectin. Both exploratory (EFA) and confirmatory factor analysis (CFA) were used to examine TG : HDL-C ratio as an IR marker in pediatric MetS. EFA shows that TG: HDL-C ratio (standardized factor loading = 0.904) groups together with homeostasis model assessment-estimated insulin resistance (HOMA-IR) (standardized factor loading = 0.664), indicating a strong correlation to the IR factor. Replacing FBG with TG: HDL-C ratio improved the modeling of MetS structure in children with obesity. Our MetS model of TG: HDL-C ratio as IR component shows comparable model fitness indices (goodness of fit, Akaike's information criterion, and Bayesian information criterion) with leptin:adiponectin ratio (platinum standard for adiposity:IR marker) model. The least model fit was seen when using FBG as an IR surrogate. TG : HDL-C ratio performed better as IR surrogate in MetS structures (standardized factor loading = 0.39) compared to FBG (standardized factor loading = 0.27). TG: HDL-C ratio may be considered as an IR component in pediatric MetS. [ABSTRACT FROM AUTHOR]

Background: Leptin may have important implications in polycystic ovary syndrome (PCOS)-related metabolic disorders. However, the changes in serum leptin levels in patients with PCOS and its predictive value for PCOS remain obscure. We intend to analyze the association between leptin and PCOS in this study. Materials and Methods: The study comprised 89 patients with PCOS and 139 individuals without PCOS. Each group was stratified as either normal- or hyper-fasting serum insulin (FSI), and lean or overweight/obese; and the patients were further categorized as normal- or hyper-androgenic. The validity of leptin toward the diagnosis of PCOS, or leptin combined with total testosterone, dehydroepiandrosterone sulfate (DHEAS), and free testosterone was estimated by receiver operating characteristic (ROC) curves, and correlations between paired variables was estimated by Spearman's rank correlation coefficient. Associations between the clinical and metabolic variables and PCOS were analyzed via logistic regression. Results: The serum leptin levels of patients with PCOS were significantly higher than that of the control, and especially the PCOS in hyper-FSI, hyperandrogenimic and overweight/obese subgroups. The area under the ROC curve (AUC) of leptin was 74%, with cutoff value, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) 11.58 ng/mL, 77.5%, 62.6%, 57.0%, and 81.3%, respectively. Combined leptin and anti-Müllerian hormone (AMH) had the highest AUC (92.3%), excellent sensitivity (93.3%), moderate specificity (78.3%), PPV (73.5%) and NPV (94.8%). Serum leptin levels of the patients were correlated with the FSI, fasting plasma glucose (FPG), homeostasis model assessment of insulin resistance (HOMA-IR), body mass index (BMI), and total testosterone levels. Elevated serum leptin was associated with a high risk of PCOS [ P = 0.015; OR (95% CI) 1.128 (1.024–1.244)]. Conclusion: Substantially elevated serum leptin is significantly associated with PCOS. These findings warrant further investigations into the function of leptin in the pathogenesis of PCOS. [ABSTRACT FROM AUTHOR]

Purpose: The correlation of abnormal glucose metabolism and thyroid carcinoma, especially the aggressiveness of thyroid cancer, still remains controversial. We conducted this study to investigate the relationship between abnormal glucose metabolism parameters and differentiated thyroid carcinoma (DTC) in the Chinese population. Materials and Methods: The study was designed as a hospital-based case–control study and was approved by the Ethics Committee of our hospital and registered in the Clinical Trial Protocol Registration and Results System (Registration code: NCT 03006289). From January 1, 2018 to June 30, 2021, a total of 377 DTC patients were enrolled in the study. Demographic and general characteristics, details of thyroid surgery and histopathological results, hematological test indicators were collected. Glucose metabolism parameters were calculated. Variables were analyzed by t-test, ANOVA, chi-squared analysis and Fisher's exact test. Pearson bi-variate correlation and Spearman's correlation analysis were used for bi-variate analysis. Results: More than 40% of patients with DTC were multifocality, more than half were extra-glandular invasion, and nearly 85% complied by lymph node metastasis. The prevalence of diabetes mellitus (DM) was about 10.08% in DTC patients. It was found that the proportion of postprandial 2 h blood glucose ≥11.1mmol/L and HbA1c ≥6.5% was significantly higher than the known proportion of DM (17.8%, 16.7% vs. 10.08%). Additionally, 87.3% of the DTC patients in this study had varying degrees of insulin resistance. Further analysis found that higher T staging was associated with higher levels of area under curve of C-peptide (P = 0.029), insulin sensitivity index (P = 0.012) and C-peptide sensitivity index (P = 0.016). A delayed peak of insulin secretion was found to be positive related with capsule invasion (r = 0.206, P = 0.004). In patients without a DM history, homeostasis model assessment of insulin resistance (P = 0.017), insulin sensitivity index (P = 0.019) and C-peptide sensitivity index (P = 0.020) were statistic associated with T staging. Also, the glucose metabolism parameter at 3-hour after a meal was related to a larger number of metastatic lymph nodes. Conclusion: Abnormal glucose metabolism, namely, DM, hyperinsulinemia and insulin resistance, were significantly associated with the carcinogensis and aggressiveness of DTC. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) plays a critical role in cardiovascular diseases and metabolic diseases. In this study, we identified the downregulation of DMRT2 in adipose tissues from insulin-resistant subjects through bioinformatics analysis and in an insulin-resistant mouse model through experimental analysis. DMRT2 overexpression significantly attenuated HDF-induced insulin resistance and inflammation in mice. Moreover, in control and insulin-resistant differentiated mouse 3T3-L1 adipocytes, DMRT2 overexpression attenuated but DMRT2 knockdown enhanced the insulin resistance of 3T3-L1 adipocytes. DMRT2 interacted with FXR and positively regulated FXR level and transcription activity. In both control and insulin-resistant differentiated mouse 3T3-L1 adipocytes, FXR knockdown enhanced the insulin resistance and attenuated the effects of DMRT2 overexpression upon 3T3-L1 adipocyte insulin resistance. In conclusion, we identify the downregulation of DMRT2 in the insulin-resistant mouse model and cell model. DMRT2 interacts with FXR and improves insulin resistance in adipocytes. [ABSTRACT FROM AUTHOR]

Background: Previous studies have shown that vitamin D3 (VD3) may be a protective factor for diabetes mellitus (DM), while triglycerides/high-density lipoprotein (TG/HDL) may be a risk factor for diabetes. However, no existing study has elucidated the interaction between TG/HDL and VD3. Therefore, this work aimed to investigate the relationships of TG/HDL with insulin resistance (IR), impaired glucose tolerance (IGT), and DM at different VD3 levels. Methods: With the use of the data from five National Health and Nutrition Examination Survey (NHANES) cycles, a total of 2,929 males and 3,031 females were divided into 4 groups according to their VD3 levels. Logistic regression was performed to observe the associations of TG/HDL ratio with IR, IGT, and DM in different groups. Results: The relationships of TG/HDL with IR, IGT, and DM showed a threshold effect, with the cutoff values of 1.094, 1.51, and 1.11, respectively. On both sides of the cutoff values, the correlation was first weakened and then enhanced with the increase in VD3 levels. Conclusion: TG/HDL is a risk factor for IR, IGT, and DM. Both too low and too high levels of VD3 can strengthen this association, whereas keeping VD3 at a reasonable level helps to reduce the associations of TG/HDL with IR, IGT, and DM. [ABSTRACT FROM AUTHOR]

Background: Attenuated insulin-sensitivity (IS) is a central feature of pediatric non-alcoholic fatty liver disease (NAFLD). We recently developed a new index, single point insulin sensitivity estimator (SPISE), based on triglycerides, high-density-lipoprotein and body-mass-index (BMI), and validated by euglycemic-hyperinsulinemic clamp-test (EHCT) in adolescents. This study aims to assess the performance of SPISE as an estimation of hepatic insulin (in-)sensitivity. Our results introduce SPISE as a novel and inexpensive index of hepatic insulin resistance, superior to established indices in children and adolescents with obesity. Materials and Methods: Ninety-nine pubertal subjects with obesity (13.5 ± 2.0 years, 59.6% males, overall mean BMI-SDS + 2.8 ± 0.6) were stratified by MRI (magnetic resonance imaging) into a NAFLD (>5% liver-fat-content; male n=41, female n=16) and non-NAFLD (≤5%; male n=18, female n=24) group. Obesity was defined according to WHO criteria (> 2 BMI-SDS). EHCT were used to determine IS in a subgroup (n=17). Receiver-operating-characteristic (ROC)-curve was performed for diagnostic ability of SPISE, HOMA-IR (homeostatic model assessment for insulin resistance), and HIRI (hepatic insulin resistance index), assuming null hypothesis of no difference in area-under-the-curve (AUC) at 0.5. Results: SPISE was lower in NAFLD (male: 4.8 ± 1.2, female: 4.5 ± 1.1) than in non-NAFLD group (male 6.0 ± 1.6, female 5.6 ± 1.5; P< 0.05 {95% confidence interval [CI]: male NAFLD 4.5, 5.2; male non-NAFLD 5.2, 6.8; female NAFLD 4.0, 5.1, female non-NAFLD 5.0, 6.2}). In males, ROC-AUC was 0.71 for SPISE (P=0.006, 95% CI: 0.54, 0.87), 0.68 for HOMA-IR (P=0.038, 95% CI: 0.48, 0.88), and 0.50 for HIRI (P=0.543, 95% CI: 0.27, 0.74). In females, ROC-AUC was 0.74 for SPISE (P=0.006), 0.59 for HOMA-IR (P=0.214), and 0.68 for HIRI (P=0.072). The optimal cutoff-level for SPISE between NAFLD and non-NAFLD patients was 5.18 overall (Youden-index: 0.35; sensitivity 0.68%, specificity 0.67%). Conclusion: SPISE is significantly lower in juvenile patients with obesity-associated NAFLD. Our results suggest that SPISE indicates hepatic IR in pediatric NAFLD patients with sensitivity and specificity superior to established indices of hepatic IR. [ABSTRACT FROM AUTHOR]

Background/Objectives: Renaming non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) suggests a shift of emphasis to the accompanying metabolic disturbance. Controlled attenuation parameter (CAP) measured by FibroScan has been shown to be correlated with hepatic steatosis. We aim to validate its usefulness as a novel surrogate marker for evaluating metabolic derangement. Subjects/Methods: Volunteers were recruited from medical staff at our hospital to undergo CAP measurements. Anthropometrics, CAP, and laboratory assessments for metabolic profiles and insulin resistance were collected. CAP < 238 dB/m denoted no hepatic steatosis, 238 ≤ CAP ≤ 259 dB/m denoted mild, 260 ≤ CAP ≤ 291 dB/m denoted moderate, and CAP > 291 dB/m denoted severe hepatic steatosis according to previous reports. Results: Data of 824 participants were included for analysis. The age was 53.2 ± 15.4 years, body mass index (BMI) was 23.6 ± 3.1 kg/m2, 24.4% were male subjects, and 22.0% met the criteria for metabolic syndrome (MetS). Taking the group with CAP < 238 dB/m as control, subjects with mild, moderate, and severe hepatic steatosis had increased odds of MetS by 3.51-, 3.32-, and 5.12-fold, respectively, after adjusting for multiple confounders (p = 0.020). Metabolic profiles, insulin resistance, and presence of MetS were similar between normal-weight subjects with CAP ≥ 238 dB/m and overweight subjects with CAP < 238 dB/m. Even in subjects with no MetS components, those with CAP ≥ 238 dB/m had higher BMI, waist circumferences, uric acid, triglyceride, white blood cell count, and insulin resistance, whereas lower adiponectin and estimated glomerular filtration rate. Waist circumference [OR 1.11 (1.04, 1.18), p = 0.001] and homeostatic model assessment of insulin resistance (HOMA-IR) [OR 2.39 (1.18, 4.83), p = 0.016] were predictive of hepatic steatosis according to CAP ≥ 238 dB/m. Conclusions: CAP is a convenient, sensitive, and non-invasive indicator for metabolic derangement. Prospective studies are needed to further validate its usefulness as a surrogate marker for the transition of metabolic status over time. [ABSTRACT FROM AUTHOR]

Aims: To determine the clinical predictors of live birth in women with polycystic ovary syndrome (PCOS) undergoing frozen-thawed embryo transfer (F-ET), and to determine whether these parameters can be used to develop a clinical nomogram model capable of predicting live birth outcomes for these women. Methods: In total, 1158 PCOS patients that were clinically pregnant following F-ET treatment were retrospectively enrolled in this study and randomly divided into the training cohort (n = 928) and the validation cohort (n = 230) at an 8:2 ratio. Relevant risk factors were selected via a logistic regression analysis approach based on the data from patients in the training cohort, and odds ratios (ORs) were calculated. A nomogram was constructed based on relevant risk factors, and its performance was assessed based on its calibration and discriminative ability. Results: In total, 20 variables were analyzed in the present study, of which five were found to be independently associated with the odds of live birth in univariate and multivariate logistic regression analyses, including advanced age, obesity, total cholesterol (TC), triglycerides (TG), and insulin resistance (IR). Having advanced age (OR:0.499, 95% confidence interval [CI]: 0.257 – 967), being obese (OR:0.506, 95% CI: 0.306 - 0.837), having higher TC levels (OR: 0.528, 95% CI: 0.423 - 0.660), having higher TG levels (OR: 0.585, 95% CI: 0.465 - 737), and exhibiting IR (OR:0.611, 95% CI: 0.416 - 0.896) were all independently associated with a reduced chance of achieving a live birth. A predictive nomogram incorporating these five variables was found to be well-calibrated and to exhibit good discriminatory capabilities, with an area under the curve (AUC) for the training group of 0.750 (95% CI, 0.709 - 0.788). In the independent validation cohort, this model also exhibited satisfactory goodness-of-fit and discriminative capabilities, with an AUC of 0.708 (95% CI, 0.615 - 0.781). Conclusions: The nomogram developed in this study may be of value as a tool for predicting the odds of live birth for PCOS patients undergoing F-ET, and has the potential to improve the efficiency of pre-transfer management. [ABSTRACT FROM AUTHOR]

Mesenchymal stromal cells (MSCs) are applied in regenerative medicine of several tissues and organs nowadays by virtue of their self-renewal capabilities, multiple differentiation capacity, potent immunomodulatory properties, and their ability to be favourably cultured and manipulated. With the continuous development of "cell-free therapy" research, MSC-derived small extracellular vesicles (MSC-sEVs) have increasingly become a research hotspot in the treatment of various diseases. Small extracellular vesicles (SEVs) are membrane vesicles with diameters of 30 to 150 nm that mediate signal transduction between adjacent or distal cells or organs by delivering non-coding RNA, protein, and DNA. The contents and effects of sEVs vary depending on the properties of the originating cell. In recent years, MSC-sEVs have been found to play an important role in the occurrence and development of diabetes mellitus as a new way of communication between cells. Diabetes mellitus is a common metabolic disease in clinic. Its complications of the heart, brain, kidney, eyes, and peripheral nerves are a serious threat to human health and has been a hot issue for clinicians. MSC-sEVs could be applied to repair or prevent damage from the complications of diabetes mellitus through anti-inflammatory effects, reduction of endoplasmic reticulum-related protein stress, polarization of M2 macrophages, and increasing autophagy. Therefore, we highly recommend that MSC-sEVs-based therapies to treat diabetes mellitus and its chronic complication be further explored. The analysis of the role and molecular mechanisms of MSC-sEVs in diabetes and its related complications will provide new idea and insights for the prevention and treatment of diabetes. [ABSTRACT FROM AUTHOR]

Aim: We aimed to detect the individual and combined effect of glucose metabolic components on cognitive function in particular domains among older adults. Methods: Data of 2,925 adults aged over 60 years from the 2011 to 2014 National Health and Nutrition Examination Survey were analyzed. Individuals' cognitive function was evaluated using the Digit Symbol Substitution Test (DSST), the Animal Fluency Test (AF), the Consortium to Establish a Registry for Alzheimer's Disease Immediate Recall (CERAD-IR), and CERAD Delayed Recall (CERAD-DR). Participants' glucose metabolic health status was determined based on fasting plasma glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), glycated hemoglobin (HbA1c), and 2-h postload glucose. Linear regression models were used to delineate the associations of cognitive function with individual glucose metabolic component and with metformin use. Logistic regression models were performed to evaluate the associations of cognition with the number of glucose metabolic risk components. Results: CERAD-IR was significantly associated with HOMA-IR and insulin. HbA1c was related to all the cognitive tests except AF. Among participants without obesity, HOMA-IR and insulin were both negatively associated with CERAD-IR and CERAD-DR. Odds of scoring low in DSST increased with the number of glucose metabolic risk components (odds ratio 1.94, 95% confidence interval [CI] 1.26 to 2.98). Metformin use was associated with better performance in DSST among diabetes patients (β = 4.184, 95% CI 1.655 to 6.713). Conclusions: Our findings support the associations of insulin resistance and glycemic level with cognitive function in key domains, especially among adults without obesity. There is a positive association between metformin use and cognition. [ABSTRACT FROM AUTHOR]

Because of the limitation of body mass index (BMI) in distinguishing adipose mass from muscle, the tri-ponderal mass index (TMI) has been proposed as a new indicator for better assessing adiposity in children and adolescents. However, it remains unclear whether TMI performs better than BMI or other adiposity indices in predicting obesity status in childhood and obesity-related cardiovascular risk factors (CVRFs) in childhood or adulthood. We searched PubMed, Cochrane Library, and Web of Science for eligible publications until June 15, 2021. A total of 32 eligible studies were included in this systematic review. We found that TMI had a similar or better ability to predict body fat among children and adolescents than BMI. However, most of the included studies suggested that TMI was similar to BMI in identifying metabolic syndrome although TMI was suggested to be a useful tool when used in combination with other indicators (e.g., BMI and waist circumference). In addition, limited evidence showed that TMI did not perform better than BMI for identifying specific CVRFs, including insulin resistance, high blood pressure, dyslipidemia, and inflammation in children and adolescents, as well as CVRFs in adults. Systematic Review Registration: https://www.crd.york.ac.uk/prospero, CRD42021260356. [ABSTRACT FROM AUTHOR]

Metformin is a drug used for the treatment of type 2 diabetes and disorders associated with insulin resistance. Metformin is also used in the treatment of pregnancy disorders such as gestational diabetes. However, the consequences of foetal exposure to metformin on the fertility of exposed offspring remain poorly documented. In this study, we investigated the effect of in utero metformin exposure on the fertility of female and male offspring. We observed that metformin is detectable in the blood of the mother and in amniotic fluid and blood of the umbilical cord. Metformin was not measurable in any tissues of the embryo, including the gonads. The effect of metformin exposure on offspring was sex specific. The adult females that had been exposed to metformin in utero presented no clear reduction in fertility. However, the adult males that had been exposed to metformin during foetal life exhibited a 30% reduction in litter size compared with controls. The lower fertility was not due to a change in sperm production or the motility of sperm. Rather, the phenotype was due to lower sperm head quality – significantly increased spermatozoa head abnormality with greater DNA damage – and hypermethylation of the genomic DNA in the spermatozoa associated with lower expression of the ten-eleven translocation methylcytosine dioxygenase 1 (TET1) protein. In conclusion, while foetal metformin exposure did not dramatically alter gonad development, these results suggest that metabolic modification by metformin during the foetal period could change the expression of epigenetic regulators such as Tet1 and perturb the genomic DNA in germ cells, changes that might contribute to a reduced fertility. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS. [ABSTRACT FROM AUTHOR]

Individuals with hepatic steatosis often display several metabolic abnormalities including insulin resistance and muscle atrophy. Previously, we found that hepatic steatosis results in an altered hepatokine secretion profile, thereby inducing skeletal muscle insulin resistance via inter-organ crosstalk. In this study, we aimed to investigate whether the altered secretion profile in the state of hepatic steatosis also induces skeletal muscle atrophy via effects on muscle protein turnover. To investigate this, eight-week-old male C57BL/6J mice were fed a chow (4.5% fat) or a high-fat diet (HFD; 45% fat) for 12 weeks to induce hepatic steatosis, after which the livers were excised and cut into ~200-µm slices. Slices were cultured to collect secretion products (conditioned medium; CM). Differentiated L6-GLUT4myc myotubes were incubated with chow or HFD CM to measure glucose uptake. Differentiated C2C12 myotubes were incubated with chow or HFD CM to measure protein synthesis and breakdown, and gene expression via RNA sequencing. Furthermore, proteomics analysis was performed in chow and HFD CM. It was found that HFD CM caused insulin resistance in L6-GLUT4myc myotubes compared with chow CM, as indicated by a blunted insulin-stimulated increase in glucose uptake. Furthermore, protein breakdown was increased in C2C12 cells incubated with HFD CM, while there was no effect on protein synthesis. RNA profiling of C2C12 cells indicated that 197 genes were differentially expressed after incubation with HFD CM, compared with chow CM, and pathway analysis showed that pathways related to anatomical structure and function were enriched. Proteomics analysis of the CM showed that 32 proteins were differentially expressed in HFD CM compared with chow CM. Pathway enrichment analysis indicated that these proteins had important functions with respect to insulin-like growth factor transport and uptake, and affect post-translational processes, including protein folding, protein secretion and protein phosphorylation. In conclusion, the results of this study support the hypothesis that secretion products from the liver contribute to the development of muscle atrophy in individuals with hepatic steatosis. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of adult GH deficiency (GHD) relies on a reduced GH response to provocative tests. Their diagnostic accuracy, however, is not perfect, and a reliable estimation of pre-test GHD probability could be helpful for a better interpretation of their results. Methods: Eighty patients showing concordant GH response to two provocative tests, i.e. the insulin tolerance test and the GHRH + arginine test, were enrolled. Data on IGF-I values and on the presence/absence of other pituitary deficits were collected and integrated for the estimation of GHD probability prior to stimulation tests. Results: An independent statistically significant association with the diagnosis of GHD was found both for IGF-I SDS (OR 0.34, 95%-CI 0.18-0.65, p=0.001) and for the presence of other pituitary deficits (OR 6.55, 95%-CI 2.06-20.83, p=0.001). A low (<25%) pre-test GHD probability could be predicted when IGF-I SDS > +0.91 in the presence of other pituitary deficits or IGF-I SDS > -0.52 in the absence of other pituitary deficits. A high (>75%) pre-test GHD probability could be predicted when IGF-I SDS < -0.82 in the presence of other pituitary deficits or IGF-I SDS < -2.26 in the absence of other pituitary deficits. Conclusion: This is the first study that proposes a quantitative estimation of GHD probability prior to stimulation tests. Our risk class stratification represents a simple tool that could be adopted for a Bayesian interpretation of stimulation test results, selecting patients who may benefit from a second stimulation test and possibly reducing the risk of wrong GHD diagnosis. [ABSTRACT FROM AUTHOR]

GLP-1 is derived from intestinal L cells, which takes effect through binding to GLP-1R and is inactivated by the enzyme dipeptidyl peptidase-4 (DPP-4). Since its discovery, GLP-1 has emerged as an incretin hormone for its facilitation in insulin release and reduction of insulin resistance (IR). However, GLP-1 possesses broader pharmacological effects including anti-inflammation, neuro-protection, regulating blood pressure (BP), and reducing lipotoxicity. These effects are interconnected to the physiological and pathological processes of Alzheimer's disease (AD), hypertension, and non-alcoholic steatohepatitis (NASH). Currently, the underlying mechanism of these effects is still not fully illustrated and a better understanding of them may help identify promising therapeutic targets of AD, hypertension, and NASH. Therefore, we focus on the biological characteristics of GLP-1, render an overview of the mechanism of GLP-1 effects in diseases, and investigate the potential of GLP-1 analogues for the treatment of related diseases in this review. [ABSTRACT FROM AUTHOR]

Background: Obesity is a multifactorial disease, which is strongly associated to other metabolic disorders. Bariatric surgery is the most effective treatment of morbid obesity. The role of beta cell function in weight loss after bariatric surgery is uncertain. Aim: To evaluate the association between beta cell function and percentage of total body weight loss (TBWL%) 1, 2, 3, and 4 years after bariatric surgery in patients with morbid obesity. Methods: Retrospective longitudinal study in patients with morbid obesity followed in our center between January 2010 and July 2018. Patients were excluded if they had diabetes at baseline or missing data on the needed parameters. We evaluated baseline Homeostatic Model Assessment of IR, Homeostatic Model Assessment of β-cell function (HOMA-beta), Quantitative Insulin Sensitivity Check Index, and Matsuda and DeFronzo index, and TBWL% at years 1 to 4. Linear regression models were used to evaluate the association of indexes of insulin resistance with TBWL% (unadjusted and adjusted for age, sex, BMI, and type of surgery). Results: There were 1,561 patients included in this analysis. HOMA-beta was negatively associated with TBWL% at second, third, and fourth years post-surgery (β = −1.04 [−1.82 to −0.26], p<0.01; β = −1.16 [−2.13 to −0.19], p=0.02; β = −1.29 [−2.64 to 0.06], p=0.061, respectively). This was not observed in the first year post-surgery nor for the other indexes. Glycemia at baseline was positively associated to EWL% at second and third years post-surgery. Conclusion: β-cell function at baseline seems to be associated to long-term weight loss, explicitly after the first year post bariatric surgery. This might be a helpful predictor of weight loss in clinical practice. [ABSTRACT FROM AUTHOR]

The increment in energy-dense food and low physical activity has contributed to the current obesity pandemic, which is more prevalent in women than in men. Insulin is an anabolic hormone that regulates the metabolism of lipids, carbohydrates, and proteins in adipose tissue, liver, and skeletal muscle. During obesity, nutrient storage capacity is dysregulated due to a reduced insulin action on its target organs, producing insulin resistance, an early marker of metabolic dysfunction. Insulin resistance in adipose tissue is central in metabolic diseases due to the critical role that this tissue plays in energy homeostasis. We focused on sexual dimorphism on the molecular mechanisms of insulin actions and their relationship with the physiology and pathophysiology of adipose tissue. Until recently, most of the physiological and pharmacological studies were done in males without considering sexual dimorphism, which is relevant. There is ample clinical and epidemiological evidence of its contribution to the establishment and progression of metabolic diseases. Sexual dimorphism is a critical and often overlooked factor that should be considered in design of sex-targeted therapeutic strategies and public health policies to address obesity and diabetes. [ABSTRACT FROM AUTHOR]

This study aims to investigate the effect of angiopoietin like 8 (ANGPTL8) on gestational diabetes mellitus (GDM) and insulin resistance (IR). The GDM model was induced by high fat diet in mice, and IR was observed. The expression and secretion of ANGPTL8 were promoted in placenta of GDM mice. IR was induced in trophoblast cell HTR-8/SVneo by treatment of high concentration of insulin, and the expression levels of ANGPTL8 were increased. Silencing of ANGPTL8 alleviated IR and decreased glucose uptake in HTR-8/SVneo cells. However, the inflammation and oxidative stress in IR cells were not restrained by ANGPTL8 knockdown. In addition, c-Jun N-terminal kinase (JNK) signaling was activated by IR, which was inhibited by silencing of ANGPTL8. The effect of ANGPTL8 knockdown on IR was attenuated by JNK antagonist, and aggravated by JNK agonist, suggesting that ANGPTL8 affected IR by regulating JNK signaling. In conclusion, we demonstrated that the silencing of ANGPTL8 ameliorated IR by inhibiting JNK signaling in trophoblast cells. These findings may provide novel insights for diagnosis and treatment of GDM in clinic. [ABSTRACT FROM AUTHOR]

Insulin resistance (IR) is largely recognized as a unifying feature that underlies metabolic dysfunction. Both lifestyle and genetic factors contribute to IR. Work from recent years has demonstrated that the epigenome may constitute an interface where different signals may converge to promote IR gene expression programs. Here, we review the current knowledge of the role of epigenetics in hepatic IR, focusing on the roles of DNA methylation and histone post-translational modifications. We discuss the broad epigenetic changes observed in the insulin resistant liver and its associated pathophysiological states and leverage on the wealth of 'omics' studies performed to discuss efforts in pinpointing specific loci that are disrupted by these changes. We envision that future studies, with increased genomic resolution and larger cohorts, will further the identification of biomarkers of early onset hepatic IR and assist the development of targeted interventions. Furthermore, there is growing evidence to suggest that persistent epigenetic marks may be acquired over prolonged exposure to disease or deleterious exposures, highlighting the need for preventative medicine and long-term lifestyle adjustments to avoid irreversible or long-term alterations in gene expression. [ABSTRACT FROM AUTHOR]

The underlying correlative mechanisms between Insulin resistance (IR) and recurrent pregnancy loss (RPL) in patients without polycystic ovarian syndrome (PCOS) remain inconclusive. To investigate the association between triglyceride (TG) levels, lymphocyte subsets, and IR in RPL patients without PCOS and obesity. Eighty-nine subjects with an unexplained RPL, independent of PCOS/obesity were enrolled in this study. A 75-g oral glucose tolerance test was performed on each subject with plasma tested for glucose and insulin. The fasting venous blood of all subjects was collected for routine clinical chemistry analysis. Lymphocyte subsets were analyzed by four-color flow cytometry. As a result, TG levels were significantly elevated in RPL patients with IR compared to those without IR. Pearson linear correlation model and receiver operating characteristic (ROC) curve analyses revealed a significant positive association between TG and HOMA-IR index value. In multiple logistic regression analysis, TG was significantly associated with the risk of hyperinsulinemia and increased CD3+CD4+/CD3+CD8+ ratio which was significantly negatively correlated with disposition index (DI30) and DI120, indicators for insulin sensitivity. In addition, DI30 and DI120 were significantly decreased in the higher CD3+CD4+/CD3+CD8+ group. Our findings showed that the elevated TG and altered immune responses in RPL patients with IR are independent of PCOS and obesity, and could be used as an indicator of IR in RPL patients. These results contribute to the understanding of the pathophysiology of IR in RPL for potential prevention and therapeutic targets. [ABSTRACT FROM AUTHOR]

Currently, Non-Alcoholic Fatty Liver Disease (NAFLD) is the most prevalent form of chronic liver disease in children and adolescents worldwide. Simultaneously to the epidemic spreading of childhood obesity, the rate of affected young has dramatically increased in the last decades with an estimated prevalence of NAFLD of 3%–10% in pediatric subjects in the world. The continuous improvement in NAFLD knowledge has significantly defined several risk factors associated to the natural history of this complex liver alteration. Among them, Insulin Resistance (IR) is certainly one of the main features. As well, not surprisingly, abnormal glucose tolerance (prediabetes and diabetes) is highly prevalent among children/adolescents with biopsy-proven NAFLD. In addition, other factors such as genetic, ethnicity, gender, age, puberty and lifestyle might affect the development and progression of hepatic alterations. However, available data are still lacking to confirm whether IR is a risk factor or a consequence of hepatic steatosis. There is also evidence that NAFLD is the hepatic manifestation of Metabolic Syndrome (MetS). In fact, NAFLD often coexist with central obesity, impaired glucose tolerance, dyslipidemia, and hypertension, which represent the main features of MetS. In this Review, main aspects of the natural history and risk factors of the disease are summarized in children and adolescents. In addition, the most relevant scientific evidence about the association between NAFLD and metabolic dysregulation, focusing on clinical, pathogenetic, and histological implication will be provided with some focuses on the main treatment options. [ABSTRACT FROM AUTHOR]

Background/Objectives: Renaming non-alcoholic fatty liver disease (NAFLD) to metabolic dysfunction-associated fatty liver disease (MAFLD) suggests a shift of emphasis to the accompanying metabolic disturbance. Controlled attenuation parameter (CAP) measured by FibroScan has been shown to be correlated with hepatic steatosis. We aim to validate its usefulness as a novel surrogate marker for evaluating metabolic derangement. Subjects/Methods: Volunteers were recruited from medical staff at our hospital to undergo CAP measurements. Anthropometrics, CAP, and laboratory assessments for metabolic profiles and insulin resistance were collected. CAP < 238 dB/m denoted no hepatic steatosis, 238 = CAP = 259 dB/m denoted mild, 260 = CAP = 291 dB/m denoted moderate, and CAP > 291 dB/m denoted severe hepatic steatosis according to previous reports. Results: Data of 824 participants were included for analysis. The age was 53.2 ± 15.4 years, body mass index (BMI) was 23.6 ± 3.1 kg/m², 24.4% were male subjects, and 22.0% met the criteria for metabolic syndrome (MetS). Taking the group with CAP < 238 dB/m as control, subjects with mild, moderate, and severe hepatic steatosis had increased odds of MetS by 3.51-, 3.32-, and 5.12-fold, respectively, after adjusting for multiple confounders (p = 0.020). Metabolic profiles, insulin resistance, and presence of MetS were similar between normal-weight subjects with CAP = 238 dB/m and overweight subjects with CAP < 238 dB/m. Even in subjects with no MetS components, those with CAP = 238 dB/m had higher BMI, waist circumferences, uric acid, triglyceride, white blood cell count, and insulin resistance, whereas lower adiponectin and estimated glomerular filtration rate. Waist circumference [OR 1.11 (1.04, 1.18), p = 0.001] and homeostatic model assessment of insulin resistance (HOMA-IR) [OR 2.39 (1.18, 4.83), p = 0.016] were predictive of hepatic steatosis according to CAP = 238 dB/m. Conclusions: CAP is a convenient, sensitive, and non-invasive indicator for metabolic derangement. Prospective studies are needed to further validate its usefulness as a surrogate marker for the transition of metabolic status over time. [ABSTRACT FROM AUTHOR]

Insulin plays a major neuroprotective and trophic function for cerebral cell population, thus countering apoptosis, beta-amyloid toxicity, and oxidative stress; favoring neuronal survival; and enhancing memory and learning processes. Insulin resistance and impaired cerebral glucose metabolism are invariantly reported in Alzheimer's disease (AD) and other neurodegenerative processes. AD is a fatal neurodegenerative disorder in which progressive glucose hypometabolism parallels to cognitive impairment. Although AD may appear and progress in virtue of multifactorial nosogenic ingredients, multiple interperpetuative and interconnected vicious circles appear to drive disease pathophysiology. The disease is primarily a metabolic/energetic disorder in which amyloid accumulation may appear as a by-product of more proximal events, especially in the late-onset form. As a bridge between AD and type 2 diabetes, activation of c-Jun N-terminal kinase (JNK) pathway with the ensued serine phosphorylation of the insulin response substrate (IRS)-1/2 may be at the crossroads of insulin resistance and its subsequent dysmetabolic consequences. Central insulin axis bankruptcy translates in neuronal vulnerability and demise. As a link in the chain of pathogenic vicious circles, mitochondrial dysfunction, oxidative stress, and peripheral/central immune-inflammation are increasingly advocated as major pathology drivers. Pharmacological interventions addressed to preserve insulin axis physiology, mitochondrial biogenesis-integral functionality, and mitophagy of diseased organelles may attenuate the adjacent spillover of free radicals that further perpetuate mitochondrial damages and catalyze inflammation. Central and/or peripheral inflammation may account for a local flood of proinflammatory cytokines that along with astrogliosis amplify insulin resistance, mitochondrial dysfunction, and oxidative stress. All these elements are endogenous stressor, pro-senescent factors that contribute to JNK activation. Taken together, these evidences incite to identify novel multi-mechanistic approaches to succeed in ameliorating this pandemic affliction. [ABSTRACT FROM AUTHOR]

Background: Small noncoding microRNA (miRNA) have regulatory functions in polycystic ovary syndrome (PCOS) that differ to those in women without PCOS. However, little is known about miRNA expression in women with PCOS who are not insulin resistant (IR). Methods: Circulating miRNAs were measured using quantitative polymerase chain reaction (qPCR) in 24 non-obese BMI and age matched women with PCOS and 24 control women. A miRNA data set was used to determine miRNA levels. Results: Women with PCOS showed a higher free androgen index (FAI) and anti-mullerian hormone (AMH) but IR did not differ. Four miRNAs (miR-1260a, miR-18b-5p, miR-424-5p, and miR let-7b-3p) differed between control and PCOS women that passed the false discovery rate (FDR) out of a total of 177 circulating miRNAs that were detected. MiRNA let-7b-3p correlated with AMH in PCOS (p < 0.05). When the groups were combined, miR-1260a correlated with FAI and let-7b-3p correlated with body mass index (BMI) (p < 0.05). There was no correlation to androgen levels. Ingenuity pathway analysis showed that nine of the top 10 miRNAs reported were associated with inflammatory pathways. Conclusion: When IR did not differ between PCOS and control women, only four miRNA differed significantly suggesting that IR may be a driver for many of the miRNA changes reported. Let-7b-3p was related to AMH in PCOS, and to BMI as a group, whilst miR-1260a correlated with FAI. Androgen levels, however, had no effect upon circulating miRNA profiles. The expressed miRNAs were associated with the inflammatory pathway involving TNF and IL6. [ABSTRACT FROM AUTHOR]

Sarcopenic obesity and diabetes are two increasing health problems worldwide, which both share many common risk factors, such as aging, and general obesity. The pathogenesis of sarcopenic obesity includes aging, physical inactivity, malnutrition, low-grade inflammation, insulin resistance, and hormonal changes. Nevertheless, there are two major reasons to cause diabetes: impaired insulin secretion and impaired insulin action. Furthermore, the individual diagnosis of obesity and sarcopenia should be combined to adequately define sarcopenic obesity. Also, the diagnosis of diabetes includes fasting plasma glucose test (FPG), 2-h oral glucose tolerance test (OGTT), glycated hemoglobin (A1C), and random plasma glucose coupled with symptoms. Healthy diet and physical activity are beneficial to both sarcopenic obesity and diabetes, but there are only recommended drugs for diabetes. This review consolidates and discusses the latest research in pathogenesis, diagnosis, and treatments of diabetes and sarcopenic obesity. [ABSTRACT FROM AUTHOR]