Circulating Asprosin Concentrations in Patients with Obesity and Carbohydrate Disturbances.

Asprosin is a fasting-induced glucogenic hormone, secreted by white adipose tissue in response to starvation. The aim of the current study was to determine the levels of asprosin in subjects from the entire spectrum of the carbohydrate metabolism. A total of 153 Causcasian subjects participated in this study: group 1, healthy volunteers; group 2, obese subjects without glycemic disturbances; group 3, subjects with prediabetes and group 4, patients with newly identified type 2 diabetes. Subject with body mass index≥30 kg/m2 and dysglycemia (prediabetes and diabetes) showed significantly high levels of asprosin (1.40 ng/ml [IQR=0.98-1.94]; 1.27 ng/ml [IQR=0.86-2.12]; 1.09 ng/ml [IQR=0.89-1.58]) compared to the control group (0.71 ng/ml [IQR=0.54-0.92]; p<0.001). Correlation analysis showed that serum asprosin also had significant positive associations with some anthropometric parameters, liver enzymes, fasting and post load glucose and insulin, LDL and triglycerides. Furthermore, we estimated a marked relationship between asprosin concentrations and intima media thickness of the common carotid artery as well as neuropathy disability and vibration sensitivity. The circulating asprosin levels for differentiating subjects with carbohydrate disturbances and those with obesity were determined by ROC analysis. The AUC for disturbances of the glucose metabolism was 0.672 (p<0.001; 95% CI=0.581-0.751) and for obesity AUC was 0.849 (p<0.001; 95% CI=0.785-0.919). Circulating asprosin could be used as a predictive factor for early carbohydrate disorders and might be a potential new therapeutic target for the treatment of dysglycemia and obesity. Further prospective studies are needed to confirm this observation.

Impact of testosterone treatment on circulating irisin in men with late-onset hypogonadism and metabolic syndrome.

OBJECTIVES: The beneficial effects of testosterone replacement therapy (TRT) in men with late-onset hypogonadism (LOH) on the body composition and metabolic outcomes are well-established. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". The aim of this study was to evaluate the effects of TRT on the levels of serum irisin in subjects with LOH. STUDY DESIGN: A total 40 men with metabolic syndrome (MS) and LOH (measured serum testosterone concentration < 12 nmol/l). TRT with Testosterone Undecanoate (Nebido™) was performed at baseline and at week 6. Irisin serum concentration was determined at baseline and at week 18 by means of ELISA. RESULTS: Circulating irisin was positively associated with serum testosterone (r = 0.283, p < 0.05). TRT has led to a statistically significant rise in circulating serum irisin levels (7.12 ± 0.76 mcg/ml versus 7.76 ± 0.75 mcg/ml; paired-samples t-test p < 0.001). ROC-analyses determined irisin to be predictive of treatment response (AUC = 0.741, p = 0.014). CONCLUSIONS: Irisin is positively associated with serum testosterone in a population of men with MS and LOH. TRT in these subjects has led to a significant improvement in associated clinical symptoms as well as to a significant rise in serum irisin levels.

Common carotid artery intima media thickness (CIMT) in patients with prediabetes and newly diagnosed type 2 diabetes mellitus.

AIM: To evaluate the relationship between common carotid artery intima media thickness (CIMT) in patients with prediabetes and new-onset diabetes mellitus without proven cardiovascular disease and some classic cardio-metabolic risk factors. PATIENTS AND METHODS: The study included 461 obese patients with an average age of 53.2 ± 10.7 years, divided into three groups - group 1 without carbohydrate disturbances (n = 182), group 2 with prediabetes (n = 193) and group 3 with newly diagnosed diabetes mellitus (n = 86). RESULTS: The patients with new-onset diabetes had significantly higher mean CIMT values compared to those with prediabetes or without carbohydrate disturbances and a higher frequency of abnormal IMT values. CIMT correlated significantly with age, systolic BP, diastolic BP and fasting blood glucose and showed a high predictive value for the presence of diabetic neuropathy and sudomotor dysfunction. Patients with abnormal CIMT values had a higher incidence of arterial hypertension, dyslipidemia, metabolic syndrome, peripheral neuropathy, and sudomotor dysfunction. Patients who developed type 2 diabetes during follow-up had a significantly higher initial mean CIMT, which showed the highest predictive value for the risk of new-onset diabetes, with CIMT≥0.7 mm having 53 % sensitivity and 83 % specificity for the risk of progression to diabetes mellitus. CONCLUSION: Patients with new-onset diabetes mellitus had significantly greater intima media thickness of the common carotid artery and a greater frequency of abnormal CIMT values compared to those with normoglycemia and prediabetes. CIMT has a high predictive value for the presence of diabetic neuropathy, sudomotor dysfunction and the risk of new onset diabetes.

IL-18 Serum Levels in Patients with Obesity, Prediabetes and Newly Diagnosed Type 2 Diabetes.

BACKGROUND: Obesity and diabetes are related to chronic low-grade inflammation. As a pro-inflammatory cytokine, IL-18 stimulates various cell types and has pleiotropic functions. OBJECTIVE: To assess the levels of IL-18 in subjects from the entire spectrum of glycemic disorders. METHODS: This study included 387 Caucasians divided into four groups: healthy controls, obese subjects without carbohydrate issues, prediabetic patients, and recently discovered type 2 diabetics. RESULTS: Subject with body mass index ≥30kg/m2 and glycemic disorders showed significantly high levels of IL-18 (249.77 ± 89.96 pg/ml; 259.01 ± 95.70 pg/ml; and 340.98 ± 127.65 pg/ml) compared with that of the control group (219.47 ± 110.53 pg/ml, p < 0.05). IL-18 also had significant positive associations with some anthropometric parameters, liver enzymes, fasting, post-load glucose, insulin, uric acid, and triglycerides while negative with HDL. The circulating IL-18 levels for differentiating subjects with carbohydrate disturbances and those with metabolic syndrome were determined by ROC analysis. The AUC for the disturbances of the carbohydrate metabolism was 0.597 (p = 0.001; 95% CI = 0.539 - 0.654) and for MS AUC was 0.581 (p = 0.021; 95 % CI = 0.516 - 0.647). CONCLUSION: Our data indicate that as the levels of IL-18 are increased the carbohydrate tolerance is deteriorated. However, the significance of IL-18 in the progression of diabetes mellitus and subsequent consequences requires further exploration.

Fibroblast Growth Factor 21 as a Marker of Prediabetes in Patients with Non-alcoholic Fatty Liver Disease.

BACKGROUND: Fibroblast growth factor 21 is a peptide primarily secreted by the liver in response to peroxisome proliferator-activated receptor-α activation which plays an important role in regulating carbohydrate and lipid metabolism. This study investigated the association between fibroblast growth factor 21 and prediabetes in obese patients with non-alcoholic fatty liver disease in adult population. METHODS: A total of 85 obese non-alcoholic fatty liver disease patients without (n = 49) and with prediabetes (n = 36) were included. Serum fibroblast growth factor 21 levels were determined by enzyme-linked immunosorbent assay. RESULTS: Higher fibroblast growth factor 21 serum levels were observed in patients with prediabetes, metabolic syndrome, dyslipidemia, and insulin resistance. There were significant correlations between fibroblast growth factor 21 and waist-to-stature ratio, visceral adiposity index, triglycerides, very low-density lipoproteins, alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), Quantitative Insulin Sensitivity Check Index, and Stumvoll index of insulin sensitivity. Fibroblast growth factor 21 level ≥320 pg/mL was associated with a 4.2-fold higher risk of prediabetes and ≥270 pg/mL for metabolic syndrome approximately 4 times. CONCLUSION: Fibroblast growth factor 21 is associated with increased risk for prediabetes, metabolic syndrome, and insulin resistance in obese patients with non-alcoholic fatty liver disease.

Relationship between circulating netrin-1 levels, obesity, prediabetes and newly diagnosed type 2 diabetes.

BACKGROUND: Netrin-1 is presumed to have regenerative, angiogenic and anti-inflammatory properties, thus it could play a substantial role in the development of insulin resistance and T2DM. OBJECTIVE: The aim of this study was to evaluate the relationship between serum netrin-1 levels and carbohydrate disturbances in patients with obesity. METHODS: Sample size consisted of 163 patients, divided into four groups: obesity without carbohydrate disturbances prediabetes and diabetes and healthy controls Netrin-1 level was determined using ELISA method. RESULTS: Circulating serum Netrin-1 was significantly lower in patients only with obesity, as well as with those with prediabetes and diabetes in comparison to the control group. Correlation analysis revealed that netrin-1 correlates negatively with BMI, waist, WSR, LDL and positive with sudomotor function. Netrin-1 ≤ 0.17 ng/ml has about 3 fold higher risk for carbohydrate disturbances (OR 3.06, 95% CI 1.48-6.34, p = .003). CONCLUSION: Netrin-1 is associated with an increased risk for glycaemic disorders in patients with obesity.

Increased Serum Pentraxin 3 Is Associated with Prediabetes and Type 2 Diabetes in Obese Patients with Nonalcoholic Fatty Liver Disease.

Background: Pentraxin 3 (PTX3) is an acute-phase protein, which resembles C-reactive protein in both structure and function, and belongs to the same family. PTX3 is associated with cardiovascular diseases, obesity, and metabolic syndrome (MetS). This study evaluated the relationship between serum PTX3 levels, prediabetes, newly diagnosed type 2 diabetes mellitus (T2DM), and other biochemical and clinical parameters in obese patients with nonalcoholic fatty liver disease (NAFLD). Methods: A total of 77 obese patients with NAFLD were included. Forty-seven of them were with normal glucose levels and 30 were with glycemic disorders, including prediabetes and newly diagnosed T2DM. Serum PTX3 was measured using ELISA method. Results: Higher PTX3 serum levels were found in patients with prediabetes and T2DM compared with those with normal blood glucose (2321.29 ± 926.63 vs. 1877.03 ± 895.45 pg/mL, P = 0.028). There were significant correlations between PTX3 and alanine aminotransferase (P = 0.018), gamma-glutamyl transferase (P = 0.005), and neuropathy disability score (P < 0.05). The presence of hypertension, dyslipidemia, insulin resistance, and MetS, as well as the number of components of the MetS did not affect PTX3 levels. Conclusions: PTX3 serum levels were higher in an obese subject with NAFLD with prediabetes and T2DM.

The association between retinol-binding protein 4 and prediabetes in obese patients with nonalcoholic fatty liver disease.

CONTEXT: Retinol-binding protein 4 (RBP4) is associated with visceral fat and insulin resistance (IR) in obesity, type 2 diabetes mellitus (T2DM) and nonalcoholic fatty liver disease (NAFLD), but some of these data remain controversial. OBJECTIVE: This study evaluated the relationship between serum RBP4 levels and prediabetes in obese patients with NAFLD. METHODS: A total of 79 obese NAFLD patients without (n = 41) and with prediabetes (n = 38) were included. Serum RBP4 was measured using ELISA method. RESULTS: Higher RBP4 serum levels were observed in patients with prediabetes, metabolic syndrome (MetS), or dyslipidaemia. There was correlation between RBP4 levels and visceral adiposity index (VAI), glucose, insulin, HOMA-IR, and Quicki index. RBP4 ≥ 61 mcg/ml have about 3.5-fold higher risk of prediabetes (OR 3.544, 95% CI 1.385-9.072, p=.008), and RBP4 ≥ 55 mcg/ml increased the risk for MetS approximately 3.1 times. CONCLUSIONS: RBP4 is associated with increased risk for prediabetes and MetS in obese patients with NAFLD.

Neopterin in the Evolution from Obesity to Prediabetes and Newly Diagnosed Type 2 Diabetes.

Background: Neopterin, marker of cellular immunity and oxidative stress, is mainly produced by activated macrophages. It could play a crucial role in the development of insulin resistance (IR) and type 2 diabetes (T2D). The aim of this study was to investigate the circulating levels of neopterin in different stages of glucose dysregulation from obesity through prediabetes to newly diagnosed diabetes. Methods: Neopterin levels were determined using a commercially available human enzyme-linked immunosorbent assay kit. The homeostasis model assessment of IR was used as an index to assess IR. Results: The sample consisted of 163 subjects with mean age 52.5 ± 11.3 years, divided in three age- and body mass index (BMI)-matched groups-obesity, prediabetes, and diabetes. The control group consisted of 42 healthy individuals. Neopterin levels were significantly higher in patients with obesity and/or prediabetes and newly diagnosed diabetes than those in the control group, respectively (4.14 ± 2.51; 4.04 ± 2.80 and 2.17 ± 1.93 vs. 0.87 ± 0.84; P < 0.05). Correlation analysis showed that the level of neopterin positively correlated with BMI, waist, waist-to-stature ratio, waist-to-hip ratio, fasting glucose, and triglycerides. Receiver operating characteristic analysis established neopterin suitable for distinguishing subjects with obesity [area under the curve (AUC) = 0.83; P < 0.001] and carbohydrate disturbances (AUC = 0.59; P < 0.05) from those without these conditions. Neopterin ≥0.47 ng/mL have an odds ratio (OR) of 2.71 for development of dysglycemia, whereas threshold value of neopterin ≥0.56 ng/mL shows an OR of 5.94 for development of obesity. Conclusion: The levels of neopterin were increased in patients with obesity and carbohydrate disturbances. Further studies will elucidate the role of the biomarker in development of T2D and its complications.

Higher levels of IL-18 in patients with prediabetes compared to obese normoglycaemic controls.

Background: Overweight and obesity are linked to low-grade chronic inflammation that can impair normal insulin function and induce insulin resistance. The aim of this study was to compare IL-18 levels between patients with prediabetes and obese normoglycaemic controls.Patients and methods: In this study, we included 131 patients with mean age 54.9 ± 9.1 years, divided into two groups - group 1 with obesity without glycaemic disturbances (n = 66) and group 2 with prediabetes (n = 65). IL-18 was measured using enzyme-linked immunosorbent assay (ELISA) method.Results: Patients with prediabetes had significantly higher levels of IL-18 compared to obese controls (304.0 ± 220.4 vs. 233.6 ± 103.6 pg/l, p=.029). When patients with prediabetes were divided into IFG only, IGT only and IFG + IGT the highest levels of IL-18 were found in IGT only patients.Conclusions: Patients with prediabetes have higher levels of IL18 compared to obese normoglycemic controls.

Lumican in Obese Patients with Nonalcoholic Fatty Liver Disease With or Without Prediabetes.

Background: Lumican is a small leucine-rich proteoglycan that regulates the assembly of collagen fibers in the extracellular matrix of different tissues. Excess collagen production in the liver is key in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) and might contribute to the risk of type 2 diabetes mellitus and cardiovascular diseases. The aim of this study was to evaluate the relationship between serum lumican and prediabetes, and other biochemical and clinical parameters in obese subjects with NAFLD. Methods: The study group included 79 subjects with obesity and NAFLD of which 41 had normal carbohydrate tolerance and 38 had prediabetes. Serum lumican was measured by means of enzyme-linked immunosorbent assay. Results: Higher lumican serum levels were found in patients with prediabetes compared with those with normal carbohydrate tolerance (0.117 ± 0.074 vs. 0.080 ± 0.048 ng/mL, P = 0.010) as well as in subjects with metabolic syndrome (MetS) versus those without MetS (0.113 ± 0.071 vs. 0.079 ± 0.048 ng/mL, P = 0.034). There was also a modest positive association between lumican levels and fasting glucose (r = 0.228, P < 0.05). Lumican levels ≥0.07 ng/mL determine a 3.9-fold higher risk of prediabetes (odds ratio: 3.945, 95% confidence interval: 1.518-10.254, P = 0.005). Conclusions: Lumican levels were higher in obese subjects with NAFLD with prediabetes and MetS. Lumican bears an increased risk for prediabetes in the study population.

PNPLA3 I148M Polymorphism in Patients with Nonalcoholic Fatty Liver Disease, Obesity and Prediabetes.

BACKGROUND AND AIMS: Nonalcoholic fatty liver disease (NAFLD) is closely associated with obesity and insulin resistance, and therefore predisposes to type 2 diabetes and cardiovascular diseases. Lipid deposition in the liver seems to be critical in the pathogenesis of NAFLD. A common genetic variant, the patatin-like phospholipase domain-containing protein 3 (PNPLA3) has been associated with NAFLD. The aim of the present study was to evaluate the association between PNPLA3, key gene of lipid metabolism and the metabolic traits in obesity NAFLD patients with and without prediabetes. METHODS: A total of 208 obese NAFLD patients without (n=125) and with prediabetes (n=83) were included. The genotyping of PNPLA3 I148M variant (rs738409) was performed by restriction analysis. RESULTS: Regarding rs738409 (I148M) polymorphism, CG genotype was positively correlated with prediabetes, insulin resistance, dyslipidemia and metabolic syndrome compared to the wild CC genotype. The carriers of the PNPLA3 I148M variant have 9.6-fold higher risk of glucose disturbances compared to wild genotype (OR 9.649, 95%CI 2.100-44.328, р=0.004). The carriers of the PNPLA3 I148M variant also have a 3 times higher risk for the presence of metabolic syndrome (OR 2.939, 95% CI: 1.590-5.434, p=0.001) and a 2.1-fold higher risk for the presence of insulin resistance (OR 2.127, 95% CI: 1.078-4.194, p=0.029). CONCLUSIONS: PNPLA3 I148M is associated with increased risk of prediabetes, metabolic syndrome and insulin resistance in obese patients with NAFLD.

Ultrasound-guided fine-needle aspiration biopsy in unselected consecutive patients with thyroid nodules.

The objective was to analyze the results of UG-FNAB, performed in unselected consecutive patients with thyroid nodules. Methods. The UG-FNAB records were analyzed in this retrospective study. Indication for biopsy was the presence of at least one nodule detected by ultrasound. Results. 330 patients at mean age ± SD 48.4 ± 11.2 years; women/men = 12.8/1 were analyzed. From the total 596 nodules found 546 (91.6%) were investigated with 1231 punctures (2.3 per nodule and 3.7 per patient). Benign solitary nodules had 42.7%, multinodular goiter (MNG) 44.8%, inconclusive 4.8%, and others 2.1% and malignant nodules 5.5% of the patients (6.6% of solitary and 5.1% of MNG patients). The risk for a separate nodule in MNG to be malignant was 2.7%. Conclusions. UG-FNAB is a safe and reliable diagnostic approach for thyroid nodules. It is the method of choice for hypo- and isoechoic not purely cystic solitary nodules, regardless of the nodule size. In MNG, its positive predictive value and diagnostic accuracy are lower. The final decision for regular US monitoring, UG-FNAB of the dominant nodule, multipuncture UG-FNAB or surgical exploration is one of complex appraisal. We consider UG-FNAB appropriate for most nodules in MNG, according to the above mentioned criteria.