Insulin Resistance Parameters Research Articles

Myonectin serum concentration changes after short-term physical activity among young, healthy people

Background: Myonectin is a myokine secreted by skeletal muscles in response to physical activity (PhA) in rodents. It was shown that myonectin may be positively associated with insulin resistance parameters. The aim of the study was to evaluate changes in the concentration of myonectin after short-term PhA. Methods: A total of 29 young, healthy volunteers, were included in the study. Each participant completed a life-style questionnaire, underwent a physical examination with anthropometric measurement followed by a treadmill test according to theBruce protocol. Blood samples were collected before and after PhA. An ELISA Assay was used to investigate the myonectin serum level. Results: The myonectin serum level did not change significantly after PhA (0.62[0.14-2.9] vs. 1.08[0.15-2.44] ng/ml; p=0.84). Before PhA the myonectin serum level differed significantly between men and women (respectively: 3.92[2.24-5.30] vs. 0.56[0.15-1.75] ng/ml; p=0.02). Before PhA it had a positive association with weight, BMI, serum creatinine and uremic acid (p < 0.05). The change in the level of myonectin serum after PhA had negative associations with weight, BMI, fasting insulin level and HOMA-IR (p < 0.05). Conclusions: Myonectin serum concentration does not change after short-term physical activity among young, healthy people. Changes in the myonectin serum level after short-term physical activity may be associated with fasting insulin resistance.

Early menarche is independently associated with subclinical hypothyroidism: a cross-sectional study

Background Subclinical hypothyroidism (SH) is more frequent in females than males, with a female to male ratio ranging from 1.5 to 5 in the general population. The aim of this study was to evaluate for the first time the association of reproductive factors, particularly age at menarche, with SH risk. Materials and methods In a cross-sectional study, reproductive factors such as age at menarche, at menopause and at first birth, lactation, parity, full-term pregnancies, reproductive years, use of oral contraceptives and hormonal replacement therapy, somatometric data and insulin resistance parameters were recorded in 72 consecutive female patients with SH and 72 healthy female controls matched on age (±5 years) and date of diagnosis (±1 month). Results SH cases exhibited significantly younger age at menarche than controls (12.6 ± 1.2 vs. 13.3 ± 0.8 years, respectively, p < 0.001). Cases presented later age at first pregnancy with a lower number of full-term pregnancies (p = 0.04). Early age at menarche was independently associated with SH risk, above and beyond thyroid autoimmunity, body mass index (BMI), hip circumference (HC), homeostatic model assessment of insulin resistance and alcohol consumption [odds ratio (OR): 0.22, 95% confidence interval (CI): 0.11-0.44; p < 0.001]. Conclusions It is possible that an interplay of early exposure to estrogens, as expressed by early menarche, and induction of thyroid autoimmunity may be associated with SH risk. More prospective studies shedding light on the role of estrogens in SH are required to confirm these findings.

Sex-specific associations between insulin resistance and bone parameters in overweight and obese older adults.

To determine sex-specific associations between insulin resistance and bone parameters measured by peripheral quantitative computed tomography in overweight and obese community-dwelling older adults. Cross-sectional study of 79 community-dwelling overweight and obese adults (mean±SD age 62.8±7.9years; body mass index 32.3±6.1kg/m2 ; 58% women). Peripheral quantitative computed tomography assessed distal radius and tibia trabecular volumetric bone mineral density (vBMD) and proximal radius and tibia cortical vBMD, periosteal circumference, endosteal circumference and stress-strain index. The Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) score was calculated from fasting glucose and insulin values. Lean mass was assessed using dual-energy X-ray absorptiometry. Total minutes of moderate and vigorous physical activity (MVPA) were calculated using the Active Australia Survey. Men and women in this cohort had no significant differences in fasting glucose and insulin concentrations, HOMA-IR valuesand diabetes prevalence (all P>0.05). In women, HOMA-IR was positively correlated with proximal radius periosteal and endosteal circumference (r=0.331; P=0.034 and r=0.325; P=0.038, respectively). These associations became nonsignificant in multivariable regression analyses; however, HOMA-IR was negatively associated with proximal radius cortical vBMD (B=-4.79; 95% CI -8.66, -0.92) after adjusting for age, lean mass and MVPA. All associations between HOMA-IR and bone parameters became nonsignificant in a sensitivity analysis excluding individuals with diabetes, or self-reported use of glucose-lowering medications. There were no associations between HOMA-IR and bone parameters in men. Homeostatic Model Assessment of Insulin Resistance was negatively associated with radial cortical vBMD in overweight and obese older women, but not in men. Further studies are needed to clarify sex-specific associations between insulin resistance and bone health in overweight and obese older adults.

SGLT-2 inhibitors in non-alcoholic fatty liver disease patients with type 2 diabetes mellitus: A systematic review.

BACKGROUNDNon-alcoholic fatty liver disease (NAFLD) is a common comorbidity with type 2 diabetes. The existing therapeutic options for NAFLD are not adequate. Hypocaloric diet and exercise is the cornerstone of therapy in NAFLD. Pioglitazone is the only drug recommended in diabetes patients with biopsy proven non-alcoholic steatohepatitis. The frequent coexistence of NAFLD and type 2 diabetes with their combined adverse health consequences and inadequate therapeutic options makes it necessary to search for newer alternatives.AIMTo assess the effect of sodium glucose cotransporter-2 (SGLT-2) inhibitors on liver enzymes in type 2 diabetes patients with NAFLD.METHODSWe searched PubMed/MEDLINE, Cochrane library, Google scholar, and Clinicaltrials.gov for the relevant articles to be included in this systematic review. Human studies done in type 2 diabetes patients with NAFLD treated with SGLT-2 inhibitors for at least 12 wk were included. Data from eight studies (four randomised controlled trials and four observational studies) were extracted and a narrative synthesis was done. A total of 214 patients were treated with SGLT-2 inhibitors in these studies (94 in randomised controlled trials and 120 in observational studies).RESULTSThe primary outcome measure was change in serum alanine aminotransferase level. Out of eight studies, seven studies showed a significant decrease in serum alanine aminotransferase level. Most of the studies revealed reduction in serum level of other liver enzymes like aspartate aminotransferase and gamma glutamyl transferase. Five studies that reported a change in hepatic fat exhibited a significant reduction in hepatic fat content in those treated with SGLT-2 inhibitors. Likewise, among the three studies that evaluated a change in indices of hepatic fibrosis, two studies revealed a significant improvement in liver fibrosis. Moreover, there was an improvement in obesity, insulin resistance, glycaemia, and lipid parameters in those subjects taking SGLT-2 inhibitors. The studies disclosed that about 17% (30/176) of the subjects taking SGLT-2 inhibitors developed adverse events and more than 40% (10/23) of them had genitourinary tract infections.CONCLUSIONBased on low to moderate quality of evidence, SGLT-2 inhibitors improve the serum level of liver enzymes, decrease liver fat, and fibrosis with additional beneficial effects on various metabolic parameters in type 2 diabetes patients with NAFLD.

HOMA-IR: An independent predictor of advanced liver fibrosis in nondiabetic non-alcoholic fatty liver disease.

Although non-alcoholic fatty liver disease (NAFLD) is common in the general population, identifying patients with advanced fibrosis remains a challenge. We investigated whether the homeostasis model assessment parameter of insulin resistance (HOMA-IR), an index of IR and one of the most important metabolic factors, is an independent predictive factor for advanced fibrosis in nondiabetic patients with NAFLD. This was a retrospective, cross-sectional multicenter study. We included 361 patients with biopsy-proven NAFLD who had not been diagnosed with type 2 diabetes mellitus: 175 (48%) were women and 48 (13%) had advanced fibrosis. We used simple random sampling; the sampling ratio of the estimation and validation groups was 7:3. A logistic model was constructed for both the estimation and validation groups. The explanatory variables were age ≥49years, sex (women), body mass index ≥26.7kg/m2 , the presence of hypertension, presence of dyslipidemia, fasting plasma glucose level≥98mg/dL, fasting immune reactive insulin level≥12.0μU/mL, and HOMA-IR≥2.90. The median HOMA-IR of the patients was 2.88 (interquartile range: 2.1-4.8). In the estimation group, univariate and multivariate analyses showed that age, dyslipidemia, and HOMA-IR were independent predictors of advanced fibrosis. In the validation group, only age and HOMA-IR were found to be independent predictors of advanced fibrosis. Homeostasis model assessment parameter of insulin resistance was an independent predictor of advanced liver fibrosis in nondiabetic patients with NAFLD. Given that most patients with NAFLD are nondiabetic, it is important to set goals with respect to improving IR to subsequently reduce liver fibrosis.

Serum chemerin levels in Polycystic Ovary Syndrome after metformin therapy

ObjectivesThe aim of this study was to study the effects of metformin therapy on serum chemerin levels in some phenotypes of polycystic ovarian syndrome cases, and to correlate chemerin levels with insulin resistance parameters and with hormonal profile. Material and methodsThis study was carried on 100 polycystic ovary cases and 70 control women. These cases were further subdivided into obese and normal weight cases. Fasting serum chemerin was measured by Enzyme-Linked Immunosorbent Assay method. Data were analyzed using SPSS for Windows 7. ResultsBefore metformin therapy, the serum chemerin were significantly increased in PCOS cases as compared with the control cases. Also, a significantly higher chemerin levels were found in obese polycystic ovarian syndrome cases as compared with normal weight cases with polycystic ovarian syndrome. The serum chemerin levels were significantly positively correlated with glucose levels, insulin levels, and HOMA-IR in polycystic ovarian syndrome cases. After three months of metformin therapy, the serum chemerin, insulin, and HOMA-IR concentrations were significantly decreased in polycystic ovarian syndrome cases as compared with the levels before therapy. ConclusionThe serum chemerin levels were significantly higher in cases of PCOS cases as compared with the controls. Metformin therapy resulted in a significant decrease in chemerin levels in polycystic ovarian syndrome cases.The analysis of Receiver Operation Characteristic curves of serum chemerin suggested that serum chemerin levels may be of value to evaluate the polycystic ovarian syndrome cases under various methods of treatments.

Adipocyte-secreted exosomal microRNA-34a inhibits M2 macrophage polarization to promote obesity-induced adipose inflammation.

Persistent, unresolved inflammation in adipose tissue is a major contributor to obesity-associated metabolic complications. However, the molecular links between lipid-overloaded adipocytes and inflammatory immune cells in obese adipose tissues remain elusive. Here we identified adipocyte-secreted microRNA-34a (miR-34a) as a key mediator through its paracrine actions on adipose-resident macrophages. The expression of miR-34a in adipose tissues was progressively increased with the development of dietary obesity. Adipose-selective or adipocyte-specific miR-34a-KO mice were resistant to obesity-induced glucose intolerance, insulin resistance, and systemic inflammation, and this was accompanied by a significant shift in polarization of adipose-resident macrophages from proinflammatory M1 to antiinflammatory M2 phenotype. Mechanistically, mature adipocyte-secreted exosomes transported miR-34a into macrophages, thereby suppressing M2 polarization by repressing the expression of Krüppel-like factor 4 (Klf4). The suppressive effects of miR-34a on M2 polarization and its stimulation of inflammatory responses were reversed by ectopic expression of Klf4 in both bone marrow-derived macrophages and adipose depots of obese mice. Furthermore, increased miR-34a expression in visceral fat of overweight/obese subjects correlated negatively with reduced Klf4 expression, but positively with the parameters of insulin resistance and metabolic inflammation. In summary, miR-34a was a key component of adipocyte-secreted exosomal vesicles that transmitted the signal of nutrient overload to the adipose-resident macrophages for exacerbation of obesity-induced systemic inflammation and metabolic dysregulation.

The influence of orlistat, metformin and diet on serum levels of insulin-like growth factor-1 in obeses women with and without insulin resistance.

A range of studies showed confusing data about the relationship between obesity, weight reduction and circulating total insulin-like growth factor -1 (IGF-1). The aim of the study was to compare the influence of orlistat (IO), metformin (IM), or calorie-restricted diet (LC) on IGF-1, with special respect to insulin-resistance status. One hundred and fourteen obese women aged from 18 to 40 years were divided into insulin sensitive (IS) and insulin resistant (IR) groups and received a low calorie diet (LC), or an isocaloric diet and 500 mg metformin twice daily (IM), or isocaloric diet with 120 mg orlistat three times daily (IO). Before and after the intervention anthropometric parameters, serum lipid profile, serum concentrations of alanine aminotransferase, aspartate aminotransferase, insulin, glucose, IGF-1, HOMA-IR (homeostatic model assessment), and visceral adiposity index (VAI), and their changes were registered. Although the reductions in weight and body fat were comparable in IS and IR groups, only women with IR showed a significant increase in IGF-1 concentration as a result of all interventions. We found significant positive correlations of ΔIGF-1 with initial and Δ values of: HOMA-IR, triglyceride/high-density cholesterol ratio, VAI. IR premenopausal women show significant increase in IGF-1 serum concentrations regardless the method of intervention. The increase in IGF-1 was parallel to the improvement of insulin resistance parameters.

Effect of High-dose Vitamin D Supplementation on Beta Cell Function in Obese Asian-Indian Children and Adolescents: A Randomized, Double Blind, Active Controlled Study.

Objective:Vitamin D deficiency has been found to be associated with insulin resistance. In an attempt to explore this association, we planned a study to investigate the effects of high-dose vitamin D supplementation on beta cell function in obese children and adolescents.Methods:A randomized, double blind, active-controlled study was carried out to investigate the effects of high dose (120,000 IU once a month) vitamin D supplementation in comparison to recommended daily allowance (12,000 IU/month) for 12 months. Beta cell function was assessed by disposition index. Inflammatory cytokines and cardiovascular risk factors were also assessed before and after supplementation.Results:A total of 189 obese children and adolescents were recruited. The mean serum 25OHD level of the study population was 8.36 ± 5.45 ng/ml. At baseline, 94.7% subjects were vitamin D deficient (<20 ng/mL). After 12 months of supplementation, serum 25OHD level in intervention group was 26.89 ± 12.23 ng/mL, while in control group, it was 13.14 ± 4.67 ng/mL (P < 0.001). No significant difference in disposition index as well as other parameters of insulin resistance, sensitivity, inflammatory cytokines, and pulse wave velocity was seen after supplementation.Conclusion:Vitamin D supplementation in doses of 120,000 IU per month for 12 months in obese Asian-Indian children and adolescents did not affect beta cell function as well as cardiovascular risk factors.

Statistical correlation of severity of coronary artery disease with insulin resistance and other clinical parameters

Objective: The objective of the study is to find the correlation of severity of coronary artery disease (Gensini score) with insulin resistance (IR) and other clinical parameters. Methods: Clinical data set (Gensini score, glycated hemoglobin, fasting insulin (FI), IR, total cholesterol, triglycerides, high-density lipoprotein, low-density lipoprotein, age, body mass index, waist circumference, high-sensitivity c-reactive protein and fasting plasma glucose) of 100 patients was collected. The individuals included in the data set were classified into four groups based on IR and phenotypic obesity. R programing language was used to find correlation between the clinical parameters and the Gensini score. Further, the data were normalized and data plot on cftools of Matlab was used to find equations to relate the parameters. The variation of Gensini score among the four groups was also analyzed. Results: The variation of Gensini score among the four groups suggests that IR can drastically increase the severity of CAD and has a more pronounced effect on the Gensini score as compared to phenotypic obesity. It was also observed that age, triglyceride levels, glycated hemoglobin, and FI had the highest positive correlation with the Gensini score, while parameters such as body mass index and high-sensitivity C-reactive protein had a higher negative correlation. Equations correlating various clinical parameters to the Gensini score were generated. Conclusion: The equations may be used to develop a software model which can predict the Gensini Score of a patient with an acceptable margin of error. As the parameters included in the study can be obtained during a regular check-up of a person, his/her risk of CAD can be predicted during the regular check-up.

The effect of 2000 ıu/day vitamin D supplementation on insulin resistance and cardiovascular risk parameters in vitamin D deficient obese adolescents.

Bilici ME, Savaş Erdeve Ş, Çetinkaya S, Aycan Z. The effect of 2000 ıu/day vitamin D supplementation on insulin resistance and cardiovascular risk parameters in vitamin D deficient obese adolescents. Turk J Pediatr 2019; 61: 723-732. The aim of this study was to determine the vitamin D deficiency prevalence in obese adolescents and to investigate the effect of vitamin D supplementation on insulin resistance and cardiovascular risk parameters in obese adolescents with vitamin D deficiency. Ninety-six obese adolescents aged 10-18 years were divided in 2 groups according to their vitamin D levels: Deficient group ( < 12ng/ ml) and sufficient group (≥12ng/ml). All patients in the vitamin D deficiency group were recommended 2000IU/day vitamin D supplementation. Fifty four (56.3%) patients had vitamin D deficiency. The only difference between the two groups was PTH level which was higher in the vitamin D deficiency group. Vitamin D reached sufficient levels in 22 (95.6%) out of the 23 patients with the 3 month supplementation of 2000 IU/day vitamin D. There was a significant decrease in weight Standard Deviation Score (SDS), Body Mass Index (BMI) SDS, hip circumference, total cholesterol, LDL, HbA1c, AST, PTH and interleukin-6 while no significant change was seen in measurements of glucose, insulin, HOMA-IR, C-peptide and the rate of metabolic syndrome. There were decreases in levels of total cholesterol and LDL with vitamin D treatment, while there was no significant change in insulin resistance. Vitamin D reduced interleukin-6 levels by its antiinflammatory effect.

Relationship between osteocalcin levels and gestational diabetes mellitus

Osteocalcin is an osteoblast-derived protein mainly acting on bone formation. There is growing evidence that osteocalcin has an important role in glucose metabolism. It was not fully elucidated in gestational diabetes mellitus. The aim of our study was to investigate osteocalcin levels in gestational diabetes mellitus and its subgroups. We performed a case�control cross sectional study and evaluated all the demographic and anthropometric parameters of 80 pregnant women whose age and body mass indices similar, half of them having normal glucose tolerance (NGT) and the other half having gestational diabetes mellitus (GDM). We compared osteocalcin, calcium metabolism parameters, glucose, lipid levels, insulin resistance parameters, and investigated correlations of all parameters in NGT and GDM. We also analyzed GDM subgroups, which were classified according to age, parity, body mass index (BMI), and vitamin D levels. Osteocalcin levels were increased in patients with GDM and in older, multiparous, with low vitamin D or high body mass index GDM subgroups but these increases were not statistically significant (P>0.05). There was a positive correlation between osteocalcin and C peptide in GDM group and also in GDM subgroups with age≥30, multiparous, vitamin D≥20 ng/ml or BMI≥30 kg/m2 (r=0.424, P=0.006; r=0.460, P=0.011; r=0.408, P=0.017; r=0.520, P=0.013; r=0.603, P=0.002 respectively). We also found a negative correlation between Osteocalcin and HDL-cholesterol in GDM and in multiparous, vitamin D≥20 ng/ml or BMI

Consumption of decaffeinated coffee protects against the development of early non-alcoholic steatohepatitis: Role of intestinal barrier function

BackgroundNon-alcoholic fatty liver disease (NAFLD) is one of the most common liver diseases worldwide lacking universally accepted therapies. Studies suggest that coffee consumption is associated with a reduced risk of NAFLD; however, molecular mechanisms and ingredients involved remain to be fully understood. Here, we determined the effects of regular intake of decaffeinated coffee on the development of NAFLD in mice, and molecular mechanisms involved. MethodsFemale C57BL/6J mice (n = 6–7/ group) were pair-fed either a liquid control diet (C) or fat-, fructose- and cholesterol-rich diet (FFC) +/- decaffeinated coffee (DeCaf, 6 g/kg BW) for 4 days or 6 weeks. Indices of liver damage, hepatic inflammation and parameters of insulin resistance and intestinal permeability as well as nitric oxide system were determined. ResultsEarly signs of insulin resistance and non-alcoholic steatohepatitis (NASH) found after 6 weeks of FFC feeding were significantly lower in FFC+DeCaf-fed mice when compared to FFC-fed animals. Moreover, elevation of portal endotoxin levels and loss of tight junction proteins in proximal small intestine found in FFC-fed mice were significantly attenuated in FFC+DeCaf-fed animals. These beneficial effects of DeCaf were associated with a protection against the significant induction of inducible NO-synthase protein levels and 3-nitrotyrosine protein adducts found in proximal small intestine of FFC-fed mice. Similar protective effects of DeCaf were also found in mice fed the FFC diet short-term. ConclusionOur results suggest that protective effects of DeCaf on the development of NAFLD are at least in part related to maintaining intestinal barrier function.

Correlation Between White Blood Cell Count and Insulin Resistance in Type 2 Diabetes.

The role of chronic inflammation in insulin resistance states and the pathogenesis of metabolic syndrome, cardiovascular disease and diabetes have been reported earlier. White Blood Cell (WBC) count is an easy marker for estimation of systemic inflammation. This study is to clarify whether WBC count is associated with insulin resistance in type 2 diabetic patients. This cross sectional study was conducted in 283 patients with type 2 diabetes and in 283 healthy non diabetic subjects as control group. Data including: age, gender, blood pressure, height and weight, history of smoking were collected for each patient. Fasting blood sugar, HbA1C, insulin, lipid profiles, creatinine, Urine albumin to creatinine ratio, high sensitive C- reactive protein (HCRP) and WBC was measured for all patients. WBC count was measured in control group. Two groups were compared in WBC count. Insulin resistance was calculated with HOMA-IR formula. Association of WBC count with insulin resistance and metabolic parameters was assessed in diabetic patients. WBC count was significantly associated with body mass index, hypertension, and triglyceride level. There was not significant association between WBC count and glycemic index and insulin resistance. An elevated WBC count (even in the normal range) is closely related to various components of metabolic syndrome but not related to insulin resistance in type 2 diabetes.

High prevalence of dyslipidemia and high atherogenic index of plasma in children and adolescents

Dyslipidemias in childhood increase the risk of cardiovascular events in adult life. To evaluate the prevalence of dyslipidemia and risk of atherogenicity based in the atherogenic index of plasma (AIP) in a sample of school children and adolescents. Cross-sectional study of 208 children aged 10.4 ± 1.0 years (107 women). Demographic data were obtained, and a clinical evaluation was conducted, including pubertal development according to Tanner and anthropometric parameters. A fasting blood sample was obtained to measure total cholesterol (CT), HDL cholesterol (cHDL) and triglycerides (TG), glucose and insulin. LDL cholesterol (cLDL), Non-HDL cholesterol and the indices CT/cHDL, cLDL/cHDL and AIP (log[TG/cHDL]) were calculated. Risk categories according to AIP for the pediatric population were also determined (low: AIP < 0.11, intermediate: AIP 0.11-0.21, high: AIP > 0.21). Thirty eight percent of participants had dyslipidemia, without differences by gender and pubertal development. The frequency of dyslipidemia was significantly higher in children with obesity (54%, p < 0.01) and a waist circumference over percentile 90 (61%; p < 0.01). The later conditions had also higher CT/cHDL, cLDL/cHDL and AIP. According to AIP, 54% of children had a high atherogenicity risk along with alterations in anthropometric parameters and insulin resistance. All anthropometric and insulin resistance parameters were significantly correlated with the AIP. There is a high prevalence of dyslipidemia in the studied population, which is associated with an increased cardiometabolic risk. The indices of atherogenicity and particularly AIP are correlated with nutritional status, abdominal obesity and parameters of insulin resistance.

Vitamin D deficiency, insulin resistance and thyroid dysfunction in obese patients: is inflammation the common link?

The aim of this article is to study the possible relation of serum vitamin D concentrations to body mass index (BMI), visceral fat thickness (VFT), insulin resistance (IR), inflammation (serum monocyte chemoattractant protein-1 – MCP-1) and thyroid parameters in obese patients. A total of 158 non-diabetic, obese patients aged 19–68 without a history of thyroid pathology were recruited. Biochemical markers, insulin, 25-OH vitamin D, thyroid parameters (TSH, FT3, FT4, TPO antibodies, TG antibodies) and VFT were measured. Serum MCP-1 evaluated the inflammation. A HOMA-IR cut-off value of 2.5 defined IR. Most patients had severe (70.3%) or moderate (25.3%) vitamin D deficiency. Vitamin D level was negatively associated with BMI (p = .043) and during the cold season with VFT (p = .009). Vitamin D deficiency correlated with Hashimoto’s thyroiditis prevalence during the warm season (p = .047) and was a risk factor for its occurrence (p = .021). At 15 ng/mL cut-off value, vitamin D was negatively correlated with MCP-1 (p = .0006). Also, MCP-1 was positive correlated with HOMA- IR (p = .042), TPO-Ab levels (p = .011) and with Hashimoto’s thyroiditis (p = .027). MCP-1 was a risk factor for vitamin D deficiency (p < .0001). Our study supports a bidirectional interaction between vitamin D and systemic inflammation in obese patients. Moreover, systemic inflammation is related to the severity and frequency of Hashimoto’s thyroiditis. Vitamin D deficiency is the single independent factor associated with Hashimoto’s thyroiditis in obese patients.

Chemerin as a biomarker at the intersection of inflammation, chemotaxis, coagulation, fibrinolysis and metabolism in resectable non-small cell lung cancer

ObjectivesChemerin is an emerging adipocytokine at the intersection of inflammation, chemotaxis, thrombosis, fibrinolysis and metabolism. Our aims were 1) to explore circulating chemerin in resectable non-small cell lung cancer (NSCLC) taking into account its several interfaces; 2) to study its diagnostic potential; and 3) to assess its associations with clinicopathological features of NSCLC. Materials and MethodsIn a large case-control study, serum chemerin, insulin resistance and lipid parameters, classic adipocytokines, inflammatory, coagulation, fibrinolysis and tumor biomarkers were determined in 110 consecutive patients with resectable NSCLC and 110 healthy controls matched on age (± 5 years), gender and date of blood draw (± 1 month). ResultsNSCLC cases exhibited significantly elevated circulating chemerin compared to controls (p < 0.001). In NSCLC cases, chemerin was positively associated with Homeostasis model assessment score of insulin resistance (HOMA-IR), fibrinogen, plasminogen activity, tumor and inflammatory biomarkers, adiponectin, number of infiltrated lymph nodes and NSCLC stage. In control participants, circulating chemerin was positively correlated with somatometric, metabolic, lipid, hemostatic and inflammatory biomarkers, and leptin. Serum chemerin was independently associated with NSCLC, above and beyond NSCLC risk factors (OR: 2.20, 95% CI: 1.09–4.40, p = 0.03). In cases, hemostatic parameters (platelet count and plasminogen activity), HOMA-IR, CYFRA 21-1, creatinine and plant food consumption emerged as independent predictors of circulating chemerin (p < 0.05). Serum chemerin greater than 220 μg/L (cut-off point) yielded a sensitivity and a specificity of 63% and 91.8% respectively with a modest discriminative ability (AUC = 0.72, 95% C.I. 0.64-0.79) for the diagnosis of NSCLC. ConclusionChemerin may represent a potentially useful biomarker in NSCLC integrating tumor-promoting networks, inflammatory and hemostatic mechanisms, and cancer-related metabolic pathways. More preclinical, prospective and longitudinal studies highlighting the pathogenetic role of chemerin in NSCLC are needed to corroborate and extend these data.

The FTO rs9939609 “A” allele is associated with impaired fasting glucose and insulin resistance in Emirati population

BackgroundFat mass and obesity-associated protein gene variants have shown diverse influence on body weight and metabolism across different populations. Overweight, obesity and metabolic syndrome are multifactorial major health problems in the UAE and worldwide. Insulin resistance represents the link between overweight and development of metabolic syndrome and type 2 diabetes mellitus. We investigated two (FTO) variants in Emirati population, in relation to insulin resistance and different parameters of metabolic syndrome. MethodsWe recruited 259 Emiratis through the UAE National Diabetes and Lifestyle Project. Ethical approval was obtained. Besides basic data collection, venous blood samples were collected. Fasting blood glucose, Lipid profile, and insulin levels were measured. Genotyping for (FTO) rs9939609 (A>T) and rs9930506 (G>A) were performed using real time-PCR. Insulin resistance were identified using HOMA2-IR calculation; with a cut-off point of 1.4 for female and 1.18 for male subjects. ResultsThe study included 259 Emiratis (age range 30–53 years, mean 41.76 years, 54.4% females), 24.5% are diabetic and 30.8% are hypertensive, with body mass index of 28.4 ± 5.9 and 28.7 ± 5.7 kg/m2 in female and male subjects, respectively. Homozygous A of rs9939609 showed significantly higher fasting glucose compared to other genotypes (p = 0.04) with a trend of higher insulin level and HOMA-2IR. The A/A diabetic patients (n = 13) showed significantly higher insulin levels compared to other genotypes. G allele of rs9930506 showed a trend of higher fasting glucose and HOMA-2IR, but lower insulin level and HbA1c. No association of genotypes was detected with other components of metabolic syndrome. ConclusionThere is an association of FTO rs9939609 A/A genotype and impaired fasting glucose and insulin resistance. Homozygous A genotype diabetic patients may be more vulnerable to blood glucose fluctuation. Focused genotyping can help the health care providers to identify high risk groups of both normal population and diabetic patients to intervene accordingly.

Increased serum concentration of ceramides in obese children with nonalcoholic fatty liver disease

BackgroundHepatic lipid accumulation is closely related to the development of insulin resistance, which is regarded as one of the most significant risk factors of nonalcoholic fatty liver disease (NAFLD). Although the exact molecular pathway leading to impaired insulin signaling has not been definitively established, ceramides are suspected mediators of lipid induced hepatic insulin resistance. Therefore, the aim of the study was to evaluate the serum ceramides concentration in obese children with NAFLD.MethodsThe prospective study included 80 obese children (aged 7–17 years, median 12 years) admitted to our Department to diagnose initially suspected liver disease. Patients with viral hepatitis (HCV, HBV, CMV), autoimmune (AIH), toxic and metabolic (Wilson’s disease, alfa-1–antitrypsin deficiency) liver diseases and celiac disease were excluded. NAFLD was diagnosed based on pediatric diagnostic criteria in obese children with liver steatosis in ultrasound (US) as well as elevated alanine transaminase (ALT) serum activity after exclusion of other major liver diseases listed before. Ultrasonography was used as a screening method and for qualitative assessment of the steatosis degree (graded according to Saverymuttu scale). Advanced steatosis was defined as a score > 1. The total intrahepatic lipid content (TILC) was assessed by magnetic resonance proton spectroscopy (1HMRS) which is the most accurate technique for assessment of ectopic fat accumulation. Fasting serum concentration of ceramides was measured in 62 children.ResultsNAFLD was diagnosed in 31 children. Significant, positive correlation was found between total serum concentration of ceramides and insulin (r = 0.3, p = 0.02) and HOMA-IR (r = 0.28, p = 0.03). Total ceramide concentration as well as specific fatty acid-ceramides (FA-ceramides) concentrations, namely: myristic, palmitic, palmitoleic, stearic, oleic, behenic and lignoceric were significantly higher (p = 0.004, p = 0.003, p = 0.007, p < 0.001, p = 0.035, p = 0.008, p = 0.003, p = 0.006, respectively) in children with NAFLD compared to controls (n = 14). Moreover, children with NAFLD had significantly higher activity of ALT (p < 0.001) and GGT (p < 0.001), HOMA-IR (p = 0.04), BMI (p = 0.046), waist circumference (p = 0.01) steatosis grade in ultrasound (p < 0.001) and TILC in 1HMRS (p < 0.001) compared to children without NAFLD. We did not find significant differences in total and FA-ceramide species concentrations between children with mild (grade 1) and advanced liver steatosis in ultrasonography (grade 2–3).ConclusionElevated ceramide concentrations in obese patients together with their significant correlation with insulin resistance parameters suggest their association with molecular pathways involved in insulin signaling impairment known to be strongly linked to pathogenesis of non-alcoholic fatty liver disease.

Rationale and Design of the STOP-OB Study for Evaluating the Effects of Tofogliflozin and Glimepiride on Fat Deposition in Type 2 Diabetes Patients Treated with Metformin/DPP-4 Inhibitor Dual Therapy.

BackgroundThe global pandemic of type 2 diabetes mellitus (T2DM) is an enormous clinical and socioeconomic burden. Biguanides and DPP-4 inhibitors (DPP-4i) are the most commonly used therapies in Japanese T2DM patients. When glycemic control is not adequate despite combination of these drugs, there is no consensus on the next step drug. Systematic reviews and meta-analyses of previous trials have indicated that glycemic control with triple combination therapies yields similar results. Thus, beneficial effects on cardiovascular risk factors may be important. The present study was designed to evaluate body fat percentage and several insulin resistance parameters after addition of tofogliflozin or glimepiride to the regimens of patients being treated with metformin and a DPP-4 inhibitor but failing to attain adequate blood glucose control.MethodsSodium glucose cotransporter-2 inhibitor, tofogliflozin versus glimepiride, comparative trial in patients with type 2 diabetes on body composition is an ongoing, multicenter, prospective, randomized, open-label, parallel-group trial. T2DM patients treated with metformin/DPP-4 inhibitor dual therapy have been recruited and randomly assigned to 20 mg/day tofogliflozin (n = 32) or 0.5 mg/day glimepiride (n = 32) groups, with either of these drugs being added to pre-existing regimens for 24 weeks.Planned OutcomesThe primary endpoint is the change in body fat percentage from baseline to 24 weeks. The secondary outcomes are changes in body composition other than fat percentage, body weight, parameters related to glycemic control and β-cell function, parameters related to lipids and arteriosclerosis, parameters related to liver function, parameters related to diabetic nephropathy, and uric acid levels. Safety parameters will also be analyzed. This is the first trial comparing the effects and safety of adding an SGLT2i and a sulfonylurea as the third-line oral agent to metformin/DPP-4i dual therapy. The results will provide valuable information for choosing third-line oral agents.Trial RegistrationUMIN000026161.FundingKowa Co. Ltd. and Kowa Pharmaceutical Co. Ltd., Tokyo, Japan.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0491-4) contains supplementary material, which is available to authorized users.