SMIM1 absence is associated with reduced energy expenditure and excess weight.

BACKGROUND: Obesity rates have nearly tripled in the past 50 years, and by 2030 more than 1 billion individuals worldwide are projected to be obese. This creates a significant economic strain due to the associated non-communicable diseases. The root cause is an energy expenditure imbalance, owing to an interplay of lifestyle, environmental, and genetic factors. Obesity has a polygenic genetic architecture; however, single genetic variants with large effect size are etiological in a minority of cases. These variants allowed the discovery of novel genes and biology relevant to weight regulation and ultimately led to the development of novel specific treatments. METHODS: We used a case-control approach to determine metabolic differences between individuals homozygous for a loss-of-function genetic variant in the small integral membrane protein 1 (SMIM1) and the general population, leveraging data from five cohorts. Metabolic characterization of SMIM1-/- individuals was performed using plasma biochemistry, calorimetric chamber, and DXA scan. FINDINGS: We found that individuals homozygous for a loss-of-function genetic variant in SMIM1 gene, underlying the blood group Vel, display excess body weight, dyslipidemia, altered leptin to adiponectin ratio, increased liver enzymes, and lower thyroid hormone levels. This was accompanied by a reduction in resting energy expenditure. CONCLUSION: This research identified a novel genetic predisposition to being overweight or obese. It highlights the need to investigate the genetic causes of obesity to select the most appropriate treatment given the large cost disparity between them. FUNDING: This work was funded by the National Institute of Health Research, British Heart Foundation, and NHS Blood and Transplant.

Chronic administration of hydrolysed pine nut oil to mice improves insulin sensitivity and glucose tolerance and increases energy expenditure via a free fatty acid receptor 4-dependent mechanism.

A healthy diet is at the forefront of measures to prevent type 2 diabetes. Certain vegetable and fish oils, such as pine nut oil (PNO), have been demonstrated to ameliorate the adverse metabolic effects of a high-fat diet. The present study investigates the involvement of the free fatty acid receptors 1 (FFAR1) and 4 (FFAR4) in the chronic activity of hydrolysed PNO (hPNO) on high-fat diet-induced obesity and insulin resistance. Male C57BL/6J wild-type, FFAR1 knockout (-/-) and FFAR4-/- mice were placed on 60 % high-fat diet for 3 months. Mice were then dosed hPNO for 24 d, during which time body composition, energy intake and expenditure, glucose tolerance and fasting plasma insulin, leptin and adiponectin were measured. hPNO improved glucose tolerance and decreased plasma insulin in the wild-type and FFAR1-/- mice, but not the FFAR4-/- mice. hPNO also decreased high-fat diet-induced body weight gain and fat mass, whilst increasing energy expenditure and plasma adiponectin. None of these effects on energy balance were statistically significant in FFAR4-/- mice, but it was not shown that they were significantly less than in wild-type mice. In conclusion, chronic hPNO supplementation reduces the metabolically detrimental effects of high-fat diet on obesity and insulin resistance in a manner that is dependent on the presence of FFAR4.

Assessment of biomarkers and clinical parameters as predictors of survival in patients with chagasic heart failure.

BACKGROUND: Chagas disease, endemic in Latin America and spreading globally due to emigration, has a significant health burden, particularly in relation to chagasic heart failure (HF). Chagasic cardiomyopathy (CCM) is characterized by chronic inflammatory myocardial disease. This study aimed to identify inflammatory parameters and biomarkers that could aid in the management of patients with chagasic HF. METHODS AND FINDINGS: A cohort study was conducted at a tertiary cardiology single-center over a mean follow-up period of 2.4 years. The study included patients with HF secondary to CCM enrolled between October 2013 and July 2017. Various clinical parameters, echocardiography findings, parasitemia status, brain natriuretic peptide (BNP) and troponin T (TnT) levels, and inflammatory biomarkers (IL-6, IL-10, IL-12p70, IL-17A, adiponectin, and IFN-γ) were assessed. The study encompassed a cohort of 103 patients, with a median age of 53 years and 70% being male. The left ventricular ejection fraction (LVEF) was 28%, with 40% of patients classified as NYHA II functional class. The median BNP level was 291 pg/ml. The observed mortality rate during the study period was 38.8%. Predictors of lower survival were identified as elevated levels of BNP, TnT, reduced LVEF, and increased adiponectin (thresholds: BNP > 309 pg/ml, TnT > 27.5 ng/ml, LVEF < 25.5%, adiponectin > 38 µg/mL). Notably, there was no evidence indicating a relationship between parasitemia and the inflammatory parameters with lower survival in these patients, including INF-γ, IL-6, IL-10, IL12-(p70), and IL17a. CONCLUSION: Despite the presence of a chronic inflammatory process, the evaluated inflammatory biomarkers in this cohort were not predictive of survival in patients with chagasic HF with reduced ejection fraction (HFrEF). However, reduced LVEF, elevated BNP, adiponectin levels, and troponin T were identified as predictors of lower survival in these patients.

Inflammatory and Metabolic Biomarker Assessment in a Randomized Presurgical Trial of Curcumin and Anthocyanin Supplements in Patients with Colorectal Adenomas.

Colorectal cancer prevention is crucial for public health, given its high mortality rates, particularly in young adults. The early detection and treatment of precancerous lesions is key to preventing carcinogenesis progression. Natural compounds like curcumin and anthocyanins show promise in impeding adenomatous polyp progression in preclinical models. We conducted a randomized, double-blind, placebo-controlled, phase II presurgical trial in 35 patients with adenomatous polyps to explore the biological effects of curcumin and anthocyanins on circulating biomarkers of inflammation and metabolism. No significant difference in biomarker changes by treatment arm was observed. However, the network analysis before treatment revealed inverse correlations between adiponectin and BMI and glycemia, as well as direct links between inflammatory biomarkers and leptin and BMI. In addition, a considerable inverse relationship between adiponectin and grade of dysplasia was detected after treatment (corr = -0.45). Finally, a significant increase in IL-6 at the end of treatment in subjects with high-grade dysplasia was also observed (p = 0.02). The combined treatment of anthocyanins and curcumin did not result in the direct modulation of circulating biomarkers of inflammation and metabolism, but revealed a complex modulation of inflammatory and metabolic biomarkers of colon carcinogenesis.

The Triglycerides-Glucose Index Shows a Stronger Correlation with Serum Adiponectin Levels than Homeostasis Model Assessment of Insulin Resistance and Quantitative Insulin Sensitivity Check Index.

Purpose: To evaluate the association between diverse surrogate markers of insulin resistance and adiponectin concentrations. Methods: Four hundred healthy participants were included. Two different cohorts were formed according to the body mass index (BMI) values. Group 1 (n = 200) consisted of individuals with normal BMI values (18.50-24.99 kg/m2), whereas in Group 2 (n = 200) there were overweight or obese individuals (BMI ≥25.00 kg/m2). Homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and triglycerides-glucose index (TyG) were calculated. Serum adiponectin levels were measured by ELISA. A correlation analysis was performed to assess the association between serum adiponectin and HOMA-IR, QUICKI, and TyG. Results: Participants in Group 2 were older (age in years: Group 1, 33.3 ± 6.8 vs. Group 2, 36.4 ± 7.0, P < 0.001). There was no gender difference between groups. Overweight or obese participants had higher BMI, waist circumference, fat mass, fat ratio, fasting plasma glucose, fasting plasma insulin, triglycerides, total cholesterol, and low-density lipoprotein cholesterol values, whereas high-density lipoprotein cholesterol was higher in participants with normal BMI measures. Overweight or obese subjects were more insulin resistant (higher TyG index and HOMA-IR) and less insulin sensitive (lower QUICKI), P < 0.001 for all. Serum adiponectin levels were lower in Group 2 (serum adiponectin in ng/mL: Group 1, 11,880 ± 6838 vs. Group 2, 9115 ± 5766, P < 0.001). The correlation between TyG index and adiponectin was stronger than the correlation between QUICKI and adiponectin, and HOMA-IR and adiponectin (r for TyG and adiponectin -0.408, r for QUICKI and adiponectin 0.394, r for HOMA-IR and adiponectin -0.268, respectively, P < 0.001 for all correlations). Conclusions: TyG has a stronger association with adiponectin than HOMA-IR and QUICKI.

Association between serum leptin concentrations and homeostasis model assessment-insulin resistance of 2.5 and higher in normal weight Japanese women.

Normal weight insulin resistant phenotype was characterized in 251 Japanese female university students using homeostasis model assessment-insulin resistance. Birth weight, body composition at age 20, cardiometabolic traits and dietary intake were compared cross-sectionally between insulin sensitive (< 1.6, n = 194) and insulin resistant (2.5 and higher, n = 16) women. BMI averaged < 21 kg/m2 and waist < 72 cm and did not differ between two groups. The percentage of macrosomia and serum absolute and fat-mass corrected leptin concentrations were higher in insulin resistant women although there was no difference in birth weight, fat mass index, trunk/leg fat ratio and serum adiponectin. In addition, resting pulse rate, serum concentrations of free fatty acids, triglycerides and remnant-like particle cholesterol were higher in insulin resistant women although HDL cholesterol and blood pressure did not differ. In multivariate logistic regression analyses, serum leptin (odds ratio:1.68, 95% confidential interval:1.08-2.63, p = 0.02) was associated with normal weight insulin resistance independently of macrosomia, free fatty acids, triglycerides, remnant-like particle cholesterol and resting pulse rate. In conclusion, normal weight IR phenotype may be associated with increased plasma leptin concentrations and leptin to fat mass ratio in young Japanese women, suggesting higher leptin production by body fat unit.

Assessment of clinical, biochemical, and radiological outcomes following intra-articular injection of Wharton jelly-derived mesenchymal stromal cells in patients with knee osteoarthritis: A prospective clinical study.

The aim of the present study was to perform clinical, biochemical, and radiological evaluation of the efficacy of mesenchymal stem cells derived from Wharton jelly (WJ) present within the human umbilical cord in the treatment of knee osteoarthritis. Between 2018 and 2019, 10 patients with knee osteoarthritis for whom the conservative treatment was not beneficial were included in the study. Patients were clinically, radiologically, and biochemically evaluated before treatment initiation. Thereafter, the patients were intra-articularly injected using a solution containing 1 × 108 WJ-derived MSCs. Evaluations were performed on day 21 (V1) and 42 (V2) and month 3 (V3), 6 (V4), and 12 (V5) after the procedure. At 1-year post-injection, visual analogue scale, Western Ontario and McMaster Universities Osteoarthritis Index, and Lequesne scores of patients were lower than those observed during the initial evaluation, whereas the mean 36-Item Short Form Health Survey score was higher. Cartilage thicknesses were found to be increased in all regions except in the medial femur, medial posterior femur, lateral posterior femur, and lateral posterior tibia regions in magnetic resonance imaging. A significant increase was observed in tumor necrosis factor-alpha, interleukin-1ß, adiponectin, resistin, and interleukin-6 levels compared with pre-injection values. The leptin levels at 6-month and 1-year controls were lower than the pre-injection levels, and the decrease observed at 6 months was significant. In patients with knee osteoarthritis, intra-articular WJ-derived MSC injection causes significant pain reduction, satisfactory functional improvement, and increased patient satisfaction following a 1-year follow-up. These clinical improvements were supported by magnetic resonance images, along with changes in adiponectin and leptin levels in synovial fluid. Level of evidence: IV.

Urbanization and Unfavorable Changes in Metabolic Profiles: A Prospective Cohort Study of Indonesian Young Adults.

The substantial increase in the prevalence of non-communicable diseases in Indonesia might be driven by rapid socio-economic development through urbanization. Here, we carried out a longitudinal 1-year follow-up study to evaluate the effect of urbanization, an important determinant of health, on metabolic profiles of young Indonesian adults. University freshmen/women in Jakarta, aged 16−25 years, who either had recently migrated from rural areas or originated from urban settings were studied. Anthropometry, dietary intake, and physical activity, as well as fasting blood glucose and insulin, leptin, and adiponectin were measured at baseline and repeated at one year follow-up. At baseline, 106 urban and 83 rural subjects were recruited, of which 81 urban and 66 rural were followed up. At baseline, rural subjects had better adiposity profiles, whole-body insulin resistance, and adipokine levels compared to their urban counterparts. After 1-year, rural subjects experienced an almost twice higher increase in BMI than urban subjects (estimate (95%CI): 1.23 (0.94; 1.52) and 0.69 (0.43; 0.95) for rural and urban subjects, respectively, Pint < 0.01). Fat intake served as the major dietary component, which partially mediates the differences in BMI between urban and rural group at baseline. It also contributed to the changes in BMI over time for both groups, although it does not explain the enhanced gain of BMI in rural subjects. A significantly higher increase of leptin/adiponectin ratio was also seen in rural subjects after 1-year of living in an urban area. In conclusion, urbanization was associated with less favorable changes in adiposity and adipokine profiles in a population of young Indonesian adults.

Adiponectin and leptin levels in idiopathic pulmonary fibrosis: A new method for BAL and serum assessment.

Adipokines (APN) are mainly secreted by adipocytes, macrophages and various other cells, along with their role in the regulation and mediation of inflammatory responses. APN is almost exclusively synthesized by adipocytes and regulated by peroxisome proliferator-activated receptor γ (PPARγ) that is involved in the epithelial-mesenchymal transition, linked lung fibrosis. Leptin is involved in acute lung injury with a role in lung fibrogenesis. Little is known about the relationship between APN/leptin and idiopathic pulmonary fibrosis (IPF) and the few studies available in the literature used ELISA to detect these lipid mediators. Our study is also the first to measure adipokines by the new multiplex assay and for the first time were performed in bronchoalveolar lavage (BAL) from IPF patients. This preliminary study suggests that APN levels in serum could be useful for predicting the prognosis of IPF, as they are inversely correlated with DLco percentages and BMI. Moreover, this first analysis of APN in BAL from IPF patients by a new method demonstrated an inverse correlation between these levels and BMI values and a direct correlation with eosinophil percentages, both of which are negative prognostic factors of IPF.

Assessment of leptin-to-adiponectin ratio in prediction of insulin resistance and nutrition status in a geriatric female population.

Both obesity and malnutrition leading to cachexia and sarcopenia are relevant risk factors in the development of many diseases. They also increase mortality, also prolong hospitalisations and convalescence, and undoubtedly increase the cost of treatment, mostly in the elderly populations. The aim of the study was to assess the relationship between the levels of leptin and adiponectin with regard to insulin resistance and malnutrition status by studying a senior female population and to evaluate predictors of insulin resistance and malnutrition. A total of 88 elderly females were enrolled prospectively with a median age of 75 years. Anthropometric and biochemical parameters (fasting glucose, insulin, folic acid, vitamin B12 concentrations, lipid profile, complete blood count) were recorded along with a full geriatric assessment, have been made in all participants. A comprehensive nutritional phenotype has been established. Leptin and adiponectin concentrations were measured by applying immunoassay techniques. Lipid profile and other parameters were performed by biochemical methods. We observed significant decreases of albumin, alanine aminotransferase, insulin, and triglycerides concentrations with age. The risk of insulin resistance based on HOMA-IR index was decreased with age. Significantly higher concentrations of leptin, leptin-to-adiponectin ratio (LAR), hsCRP, fasting glucose, insulin in the insulin resistant subgroup in respect of normal sensitivity insulin cases were noted. The concentrations of albumin, aspartate aminotransferase, alanine aminotransferase and total cholesterol were significantly lower in those patients at risk of malnutrition than in the well-nourished subjects. LAR reached the most accurate AUCROC = 0.705 for insulin resistance prediction, with a cut-off value at 3.85. The greatest diagnostic power was presented by the albumin concentration with AUCROC = 0.761 and then LAR 0.718 in discriminating between well-nourished patients and those at risk of malnutrition. We suggest that the leptin-to-adiponectin ratio is suitable as a marker of insulin resistance and nutritional status in the elderly.

Sex-Specific Regulation of Inflammation and Metabolic Syndrome in Obesity.

OBJECTIVE: Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m2 and half with a BMI>30 kg/m2, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. CONCLUSIONS: We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.

Role of adipokines in the assessment of severity and predicting the clinical course of acute pancreatitis.

Acute pancreatitis (AP) is one of the most common diseases requiring hospitalization with increasing incidence. This pathology has variable severity and is associated with significant morbidity and mortality. Early diagnosis, including prognosis of clinical course of the disease is key in the initial clinical management. However, currently available prognostic markers have variable efficacy and the limited utility. Adipokines that are released from the peripancreatic adipose tissue during AP may represent the easy to use and practical AP prognostic markers. This review discusses the current state of knowledge concerning the clinical value of the adipokines in AP, such as adiponectin, ghrelin, interleukin 6, interleukin 8, interleukin 18, leptin, neutrophil gelatinase associated lipocalin, obestatin, resistin, visfatin. Among described adipokines, interleukin 6, neutrophil gelatinase associated lipocalin and resistin seem to be the most valuable as the diagnostic and prognostic markers in AP.

Factors influencing bone loss in anorexia nervosa: assessment and therapeutic options.

Decreased mineral density is one of the major complications of anorexia nervosa. The phenomenon is even more pronounced when the disease occurs during adolescence and when the duration of amenorrhoea is long. The mechanisms underlying bone loss in anorexia are complex. Oestrogen deficiency has long been considered as the main factor, but cannot explain the phenomenon on its own. The essential role of nutrition-related factors-especially leptin and adiponectin-has been reported in recent studies. Therapeutic strategies to mitigate bone involvement in anorexia are still a matter for debate. Although resumption of menses and weight recovery appear to be essential, they are not always accompanied by a total reversal of bone loss. There are no studies in the literature demonstrating that oestrogen treatment is effective, and the best results seem to have been obtained with agents that induce bone formation-such as IGF-1-especially when associated with oestrogen. As such, bone management in anorexia remains difficult, hence, the importance of early detection and multidisciplinary follow-up.

Assessment of selected adipocytokines in obese women with postmenopausal osteoporosis.

INTRODUCTION: Osteoporosis and obesity are considered civilisation diseases. Menopause is a time of increased bone resorption and increased mass of adipose tissue. Adipocytokines secreted by the adipose tissue are believed to be a potential factor in the pathogenesis of osteoporosis. MATERIAL AND METHODS: The aim of this research was to assess leptin, adiponectin, and resistin secretion in obese postmenopausal women with osteoporosis and determine whether obesity might be a factor mitigating the risk of osteoporosis. The study involved 80 postmenopausal women with osteoporosis divided into groups: I with BMI of 30.0 34.9, obese; and II with BMI of 18-24.9, normoweight. Leptin, adiponectin and resistin concentrations were assessed, and bone mineral density (BMD) was measured in the L1-L4 section of the spine using the DXA densitometric method. RESULTS: The results of the comparison of the two groups indicate a statistically significant dependence in groups regarding leptin secretion; the group of obese women demonstrated significantly higher concentrations. No differences between the groups were demonstrated for adiponectin or resistin secretion. CONCLUSIONS: Higher leptin concentration and a positive correlation with BMI was confirmed in obese postmenopausal women with osteoporosis. It was also demonstrated that BMD increases with growing BMI. No effect of obesity on the secretion of adiponectin or resistin in women with postmenopausal osteoporosis was found. From among the investigated adipocytokines, only leptin can be considered a bone tissue protective factor in postmenopausal women.

Assessment of autonomic functions and its association with telomerase level, oxidative stress and inflammation in complete glycemic spectrum- an exploratory study.

AIMS: In the present study we intended to study autonomic functions and its association with telomerase level, oxidative stress and inflammation in complete glycemic spectrum. MATERIALS AND METHODS: Age, gender and BMI matched 28 subjects in the age group of 25-50 years were recruited across complete glycemic spectrum as follows: 1) Normoglycemics (controls) 2) Prediabetics and 3) Frank diabetics. We assessed heart rate variability, cardiac autonomic function, lipid profile, adiponectin, malondialdehyde and telomerase level. RESULTS: Time domain parameters and frequency domain parameters were significantly lower, and LFnu and LF/HF ratio were significantly higher in prediabetes and diabetes than control. Serum Adiponectin and HDL levels were significantly lower in diabetes than prediabetes and control, and prediabetes had significantly lower HDL than controls. Other lipid profile parameters (TC, TG, VLDL, LDL, non-HDL & derived lipid parameters were significantly higher in diabetes than prediabetes and control and prediabetes had significantly higher values than controls. MDA levels were significantly higher and TAS was significantly lower in diabetics than prediabetics and control group. Telomerase level was significantly higher in diabetes as compared to prediabetes and control. Telomerase had significantly negative correlation with SDNN, HF, TP, HDL and adiponectin, and significant positive correlation with MDA, fasting insulin, HOMA IR, TC, and AIP. CONCLUSION: Oxidative damage, inflammation and autonomic dysregulation may be involved in Telomere/Telomerase dysregulation in diabetes and telomerase levels can be used as a cardio-metabolic marker of diabetes.

Assessment of the Relationship Between Serum High Molecular Weight Adiponectin Hormone Levels and Insulin Resistance in Patients with Polycystic Ovary Syndrome.

The purpose of this study was to assess the rate of insulin resistance (IR) and the relationship between IR and high-molecular weight adiponectin (HMWA) in patients with polycystic ovary syndrome (PCOS). A cross sectional study involving 43 women with PCOS and 39 normal women was carried out over a period of nine months. Fasting glucose and insulin levels, lipid parameters and androgen levels were measured in all serum samples. HMWA was determined by enzyme-linked immunosorbent assay and IR was estimated using the homeostasis model assessment of insulin resistance (HOMA-IR) index. The IR was more prevalent in the PCOS group than in the controls (p=0.002). Dehydroepiandrosterone sulfate, sex hormone binding globulin, free androgen index, total testosterone, insulin, and HOMA-IR levels were significantly higher in the PCOS group as compared to the control group (all p<0.05). Moreover, HMWA was significantly lower and negatively correlated with the clinical and biochemical hyperandrogenism in the PCOS group. HMWA and HOMA-IR were also associated with triglyceride, body mass index, and fat mass in this group. ROC curve analyses demonstrated that the AUC, indicative of the HMWA value for discriminating PCOS with IR, was 0.725, with a confidence interval of 0.615-0.835 (p=0.001). The serum HMWA levels are lower in patients with PCOS, which suggest that HMWA might be involved in the pathogenesis of PCOS. We also conclude that HMWA might be a strong determinant of IR in PCOS patients.

Homeostatic model assessment of adiponectin (HOMA-Adiponectin) as a surrogate measure of insulin resistance in adolescents: Comparison with the hyperglycaemic clamp and homeostatic model assessment of insulin resistance.

BACKGROUND: Studies on adults have reported inverse association between the homeostatic model assessment (HOMA) of adiponectin (HOMA-Adiponectin) and the insulin resistance assessed by the glucose clamp technique. To our knowledge, in the pediatric population this association has not been previously investigated. OBJECTIVES: To evaluate the association between the HOMA-Adiponectin and the insulin resistance assessed by the glucose clamp technique in adolescents, and to compare the accuracy of HOMA-Adiponectin and HOMA-insulin resistance (HOMA-IR) for identifying insulin resistance. METHODS: This was a cross-sectional study of 56 adolescents (aged 10-18 years). Insulin resistance was assessed using the HOMA-IR, HOMA-Adiponectin and the hyperglycaemic clamp technique. The clamp-derived insulin sensitivity index, HOMA-Adiponectin, and HOMA-IR were log-transformed to get closer to a normal distribution before analysis. RESULTS: In the multivariable linear regression analysis controlling for sex and Tanner stage, HOMA-Adiponectin was inversely associated with the clamp-derived insulin sensitivity index (unstandardized coefficient [B] = -0.441; P < 0.001). After additional adjustment for waist circumference-to-height ratio, this association remained significant (B = -0.349; P = < 0.001). Similar results were observed when HOMA-IR replaced HOMA-Adiponectin in the model (B = -1.049 and B = -0.968 after additional adjustment for waist circumference-to-height ratio); all P < 0.001. The area under the receiver operating characteristic curve for predicting insulin resistance was 0.712 (P = 0.02) for HOMA-Adiponectin and 0.859 (P < 0.0001) HOMA-IR. CONCLUSIONS: The HOMA-Adiponectin was independently associated with insulin resistance and exhibited a good discriminatory power for predicting it. However, it did not show superiority over HOMA-IR in the diagnostic accuracy.

Assessment of apelin, apelin receptor, resistin, and adiponectin levels in the primary tumor and serum of patients with esophageal squamous cell carcinoma.

BACKGROUND: Disturbances in adipokine secretion are associated with the risk of cancer growth and progression. OBJECTIVES: The aim of the study was to evaluate the mRNA expression and protein levels of apelin, the apelin receptor, resistin, and adiponectin in the tumor tissues of surgically treated esophageal squamous cell carcinoma (ESCC) patients. Concentrations of serum adipokines were assessed in relation to ESCC progression. MATERIAL AND METHODS: The study group consisted of 53 patients with ESCC and 27 controls. In the ESCC group, 27 patients were surgically treated and 26 were treated with palliative procedures. RT-PCR and ELISA tests were used to measure the mRNA expression and protein level of adipokines in tissues and their concentration in serum. RESULTS: We found that mRNA expression and protein concentrations of apelin, the apelin receptor and resistin were significantly higher in tumor tissue than in control tissue. The protein concentration of apelin were significantly increased in the tumors of patients with lymph node metastasis (p < 0.005). Circulating levels of apelin, the apelin receptor and resistin were significantly higher in the cancer patients than in controls (p < 0.05 for all). The concentration of serum apelin receptor significantly decreased in patients with stage IV cancer, the presence of lymph node or distant metastasis (p < 0.05). CONCLUSIONS: Apelin may participate in lymphangiogenesis and the progression of ESCC. The apelin receptor is intensely produced in the early stage of cancer development and it may take part in the carcinogenic processes of ESCC.

A Novel Early Pregnancy Risk Prediction Model for Gestational Diabetes Mellitus.

INTRODUCTION: Accurate early risk prediction for gestational diabetes mellitus (GDM) would target intervention and prevention in women at the highest risk. We evaluated novel biomarker predictors to develop a first-trimester risk prediction model in a large multiethnic cohort. METHODS: Maternal clinical, aneuploidy and pre-eclampsia screening markers (PAPP-A, free hCGß, mean arterial pressure, uterine artery pulsatility index) were measured prospectively at 11-13+6 weeks' gestation in 980 women (248 with GDM; 732 controls). Nonfasting glucose, lipids, adiponectin, leptin, lipocalin-2, and plasminogen activator inhibitor-2 were measured on banked serum. The relationship between marker multiples-of-the-median and GDM was examined with multivariate regression. Model predictive performance for early (< 24 weeks' gestation) and overall GDM diagnosis was evaluated by receiver operating characteristic curves. RESULTS: Glucose, triglycerides, leptin, and lipocalin-2 were higher, while adiponectin was lower, in GDM (p < 0.05). Lipocalin-2 performed best in Caucasians, and triglycerides in South Asians with GDM. Family history of diabetes, previous GDM, South/East Asian ethnicity, parity, BMI, PAPP-A, triglycerides, and lipocalin-2 were significant independent GDM predictors (all p < 0.01), achieving an area under the curve of 0.91 (95% confidence interval [CI] 0.89-0.94) overall, and 0.93 (95% CI 0.89-0.96) for early GDM, in a combined multivariate prediction model. CONCLUSIONS: A first-trimester risk prediction model, which incorporates novel maternal lipid markers, accurately identifies women at high risk of GDM, including early GDM.

Serum cytokines, adipokines and ferritin for non-invasive assessment of liver fibrosis in chronic liver disease: a systematic review.

Chronic liver disease (CLD) is a major health problem worldwide. Non-alcoholic fatty liver disease (NAFLD), chronic hepatitis C (CHC), chronic hepatitis B (CHB), and alcoholic liver disease (ALD) are the most common etiologies of CLD. Liver biopsy is the gold standard for assessment of liver fibrosis, however, it is an invasive method. This review attempts to evaluate the usefulness of serum adiponectin, serum leptin, serum ferritin, serum transforming growth factor-ß1 (TGF-ß1), and serum platelet derived growth factor-BB (PDGF-BB) as non-invasive markers in the diagnosis of liver fibrosis/cirrhosis. A systematic search in MEDLINE, Web of Science, Scopus, and local databases was performed to identify articles published in English or Persian as of November 2017. Studies conducted among CLD patients, with biopsy proven fibrosis/cirrhosis, and providing sufficient details of patients' clinicopathological characteristics were included. In the 95 studies included, there were a total of 15,548 CLD patients. More than 83% of studies were carried out in Asia and Europe. The relationship between liver fibrosis/cirrhosis and serum levels of ferritin, adiponectin, leptin, TGF-ß1, and PDGF-BB was assessed in 42, 33, 27, nine, and three studies, respectively. Serum levels of the markers, particularly ferritin, could successfully predict liver fibrosis/cirrhosis, however, these data might not be clinically replicated and further studies are needed.