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.

Meteorin-like Protein and Zonulin in Polycystic Ovary Syndrome: Exploring Associations with Obesity, Metabolic Parameters, and Inflammation.

OBJECTIVE: Polycystic ovary syndrome (PCOS) is a prevalent hormonal and metabolic disorder, wherein the adipose tissue and gut microbiome have been demonstrated to contribute to its pathogenesis. This study aims to assess the concentrations of the adipokine, meteorin-like protein (Metrnl) and the protein, zonulin, related to intestine permeability, in individuals with PCOS with a particular emphasis on their relationship with obesity, clinical manifestations, hormonal profiles, and metabolic parameters. METHODS: A cohort comprising 58 women with PCOS, classified according to the Rotterdam criteria, was enrolled. The study also considered age, body mass index (BMI), and ethnicity-matched controls (n = 30). Comprehensive anthropometric and clinical evaluations, hormonal assays, and biochemical analyses were conducted during the follicular phase. Subsequent subgroup analyses were executed within the PCOS cohort based on waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum concentrations of Metrnl and zonulin were quantified via the enzyme-linked immunosorbent assay (ELISA) technique. RESULTS: The Metrnl and zonulin levels exhibited no significant disparity between PCOS patients and controls. Nevertheless, within the entire participant cohort and the PCOS group exclusively, overweight/obese participants demonstrated higher Metrnl concentrations relative to their normal-weight counterparts (p < 0.001, p = 0.001, respectively). Furthermore, higher Metrnl concentrations were identified in subgroups characterized by high WHtR and IR in comparison to those with low WHtR (p = 0.001) and without IR (p = 0.001), respectively. A correlation emerged between Metrnl levels and various anthropometric and metabolic parameters, as well as sex-hormone-binding globulin (SHBG) and interleukin-18 (IL-18) within the PCOS group. Multiple linear regression analysis identified HOMA-IR as the sole independent predictor of Metrnl levels. CONCLUSION: While Metrnl and zonulin levels do not serve as diagnostic indicators of PCOS, elevated Metrnl concentrations exhibited robust associations with proinflammatory and metabolic irregularities within the PCOS population.

Comparing the Efficacy of Myo-Inositol Plus α-Lactalbumin vs. Myo-Inositol Alone on Reproductive and Metabolic Disturbances of Polycystic Ovary Syndrome.

Despite the beneficial effect of myo-inositol on metabolic, hormonal, and reproductive parameters of polycystic ovary syndrome (PCOS) patients, 28% to 38% could be resistant to this treatment. The combination with the milk protein α-lactalbumin can be a useful therapeutic approach to overcome inositol resistance and achieve ovulation in these women. This open-label prospective study aimed to compare the effects of supplementing myo-inositol plus α-lactalbumin vs myo-inositol alone on reproductive and metabolic abnormalities in PCOS. A total of 50 anovulatory women with a PCOS diagnosis were randomly assigned to receive myo-inositol alone or a combination of myo-inositol and α-lactalbumin for three months. Anthropometric measures, hormonal levels, and menstrual cycle duration were collected at baseline and after treatment. The therapy with myo-inositol plus α-lactalbumin improved both ovulation rate and menstrual cycle duration more than myo-inositol alone. The body weight was significantly reduced in women receiving myo-inositol plus α-lactalbumin, while patients in the myo-inositol group experienced no change. In addition, the improvement of hyperandrogenism was more prominent in patients treated with myo-inositol plus α-lactalbumin. The benefits of associating myo-inositol and α-lactalbumin clearly make this combination a true edge in the management of PCOS.

Usefulness of different adiposity indexes for identification of metabolic disturbances in patients with obesity.

CONTEXT: Despite the role of BMI as a classical obesity index, other indexes reflecting mainly abdominal obesity, usually outperform BMI in terms of metabolic complications prediction. OBJECTIVE: The aim of the present study is to compare the usefulness of different adiposity indexes for the identification of metabolic disturbances in patients with obesity. METHODS: In the study, we included 461 patients - group 1 with obesity (n = 182), group 2 with prediabetes (n = 193), and group 3 with newly diagnosed type 2 diabetes (n = 86). Different anthropometric and adiposity indexes were calculated - WHR, WSR, VAI, ABSI, BRI, Hip index, WWI, LAP. RESULTS: VAI and LAP had the highest predictive value for the presence of carbohydrate disturbances. VAI also showed the strongest correlation with Framingham and SCORE compared to other adiposity indexes. CONCLUSIONS: VAI and LAP are most useful for the identification of metabolic disturbances and cardiovascular risk in patients with obesity.

Analysis of 2-Arachidonoylglycerol Levels in Polycystic Ovary Syndrome in the Context of Hormonal and Metabolic Alterations and Across the Classical Phenotypes.

Introduction: Ovarian folliculogenesis requires a fine balance between extra- and intra-ovarian factors. Endocannabinoids are found in the female reproductive system and are essential for a normal follicular growing process and ovulation. First, our study aimed to analyze levels of the endocannabinoid-2-arachidonoylglycerol (2-AG)-in patients with polycystic ovary syndrome (PCOS) and to compare with healthy controls. In addition, the study aimed to explore the association of 2-AG with hormonal and metabolic alterations, ovulatory dysfunction, and the presence of polycystic ovarian morphology (PCOM) across the classical PCOS phenotypes. Methods: Fifty-four women with PCOS were compared with 26 healthy controls. PCOS patients were diagnosed and phenotyped according to the Rotterdam criteria. Further analyses were performed with the classical PCOS phenotypes A and B comprising hyperandrogenism with oligo-anovulation with or without PCOM, respectively. Full medical history, clinical investigations, anthropometric measurements, laboratory tests, and ultrasound investigations were carried out in the follicular phase. Serum levels of 2-AG were measured by enzyme-linked immunosorbent assay. Results: PCOS patients (n=54) and healthy controls (n=26) showed similar metabolic parameters and anthropometric characteristics. PCOS patients were more hirsute than healthy women (p=0.001). Luteinizing hormone/follicle-stimulating hormone ratio and serum levels of androgens were significantly higher in the patient than in the control group (p=0.035, p<0.001, respectively). Free androgen index was also higher in the patient group (p=0.002). Serum levels of 2-AG did not significantly differ when comparing all PCOS patients versus healthy controls; however, further analysis of individual phenotype groups revealed that 2-AG levels in PCOS patients with phenotyope A (n=30) were significantly lower when compared with PCOS patients with phenotype B (n=20) and healthy controls (n=26). Conclusion: Serum levels of 2-AG were similar between PCOS patients and healthy controls. Nevertheless, phenotype A PCOS patients had significantly lower levels of the endocannabinoid compared with phenotype B patients and healthy controls. Collectively, these results suggest that overall serum levels of 2-AG are not a diagnostic marker for PCOS; however, their altered secretion or activity may influence normal follicular processes.

Anandamide is associated with waist-to-hip ratio but not with Body Mass Index in women with polycystic ovary syndrome.

BACKGROUND: The endocannabinoid system is involved in the regulation of energy balance and ovarian function and may be implicated in the pathogenesis of polycystic ovary syndrome (PCOS). The purpose of the present study is to determine anandamide (AEA) levels in PCOS patients and controls and to analyze its association with metabolic and hormonal disturbances in women with PCOS. METHODS: The study included 88 women - 58 patients with PCOS (25.9±5.2 years) and 30 healthy controls (27.6±5.2 years). Further, patients were divided into two subgroups according to their waist-to-hip ratio (WHR): android type PCOS (WHR≥0.85; N.=26) and gynoid type PCOS (WHR<0.85; N.=32). Detailed anthropometric measurements, hormonal and biochemical tests and pelvic ultrasound were obtained between the 3rd and 5th day of a menstrual cycle. AEA was examined by ELISA kits. RESULTS: Patients with PCOS and healthy controls did not differ in anthropometric, metabolic parameters, AEA, and sex hormone-binding globulin (SHBG) levels. The PCOS group had increased total testosterone, FAI, DHEAS, androstenedione, and 17-OH-progesterone levels (P<0.001) and elevated LH/FSH ratio (P=0.023). A negative correlation between AEA levels was found with glycaemia at 120 minutes (r=-0.304, P=0.020) and WHR (r=-0.266, P=0.044). In the subanalysis of patients, the gynoid type group had significantly higher levels of AEA than the android type PCOS (5.4 [2.3;8.8] vs. 2.5 [1.8;5.1]; P=0.020). CONCLUSIONS: AEA did not differ between healthy women and patients, but a significant difference in its levels was found in PCOS patients divided according to their body constitution type.

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.

Elevated levels of interleukin-18 are associated with several indices of general and visceral adiposity and insulin resistance in women with polycystic ovary syndrome.

Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics. Methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3rd and 5th day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method. Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18. Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.

Cardiac Autonomic Neuropathy in Patients with Newly Diagnosed Carbohydrate Disturbances.

Cardiac autonomic neuropathy (CAN) is a serious complication of diabetes mellitus that can predispose patients to higher risk for cardiovascular death. The aim of the present study was to evaluate the presence of cardiac autonomic neuropathy and sudomotor dysfunction in patients with newly diagnosed carbohydrate disturbances (prediabetes or diabetes) and to assess their relationship to metabolic disturbances and cardiovascular risk. In the present study, we included 160 patients -78 with obesity without carbohydrate disturbances, 52 with prediabetes, and 30 with newly diagnosed diabetes. CAN was diagnosed using cardiovascular reflex tests and sudomotor function was evaluated by SUDOSCAN. Cardiovascular risk was calculated using SCORE and FRMINGHAM risk scores. The prevalence of cardiac autonomic neuropathy was significantly higher in patients with newly diagnosed diabetes. Independently of their glycemic status, the patients who had blood glucose on the 60th-minute of OGTT>8.5 mmol/l had significantly higher prevalence of cardiac autonomic neuropathy (30.2% vs 15.6%, р=0.044). Patients with high cardiovascular risk according to FRAMINGHAM and SCORE had worse heart rate variability scores. Autonomic neuropathy risk assessed by SUDOSCAN was a good predictor for the presence of CAN. In conclusion, CAN has a higher prevalence on patients with newly diagnosed diabetes compared to prediabetic and normoglycemic subjects, while the patients with blood glucose>8.5 mmol/l on the 60th-minute of OGTT have higher prevalence of CAN independently of their glycemic status. SUDOSCAN testing can be used to assess the risk of CAN and to select patients that should undergo further testing.

Elevated levels of interleukin-18 are associated with several indices of general and visceral adiposity and insulin resistance in women with polycystic ovary syndrome

ABSTRACT Objective: Our aim was to analyze levels of proinflammatory biomarker interleukin-18 (IL-18) in healthy controls and patients with polycystic ovary syndrome (PCOS) focusing on its association with obesity, clinical, hormonal, and metabolic characteristics. Subjects and methods: Fifty-eight patients with PCOS were enrolled in the study fulfilling the Rotterdam criteria and were matched for age, body mass index (BMI), and ethnicity with 30 healthy controls. Detailed anthropometric measurements, clinical investigations, hormonal and biochemical tests were obtained between the 3rd and 5th day of a menstrual cycle. A subanalysis of the PCOS group was performed separating patients into several groups according to a waist-to-height ratio (WHtR), insulin resistance (IR), and free androgen index (FAI). Serum IL-18 levels were measured using the ELISA method. Results: Levels of IL-18 were similar between PCOS patients and controls. IL-18 was higher in overweight/obese women compared to normal-weight women when analyzing all participants together and separately PCOS or controls group (p < 0.001, p < 0.001, p = 0.01, respectively). Additionally, IL-18 levels were higher in high-WHtR and IR subgroups compared to low-WHtR (p < 0.001) and non-IR PCOS women (p < 0.001). PCOS women with high FAI had greater serum IL-18 levels than normal-FAI patients (p = 0.002). Levels of IL-18 correlated positively with most of the anthropometric and metabolic parameters. In multiple linear regression, age, waist circumference, and fasting insulin were independently related factors with IL-18. Conclusion: Elevated levels of IL-18 were related to several indices of general and visceral adiposity and insulin resistance in PCOS.

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.

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.

Polycystic ovary syndrome and (pre)osteoarthritis: assessing the link between hyperandrogenism in young women and cartilage oligomeric matrix protein as a marker of cartilage breakdown.

INTRODUCTION: OBJECTIVES: Our aim was to analyze the link between hyperandrogenism and early clinical manifestations of osteoarthritis (OA), knee cartilage thickness, and serum cartilage oligomeric matrix protein (sCOMP) levels in patients with polycystic ovary syndrome (PCOS) and to compare them with healthy volunteers. METHODS: Fifty-four PCOS patients who met the Rotterdam criteria with phenotypes A, B, and C were included. They were compared with 26 age- and body mass index (BMI)-matched controls. Detailed anthropometric measurements and clinical evaluation for hyperandrogenism were performed for all participants who also filled in the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire. Furthermore, laboratory tests including sCOMP and hormone quantification were performed in a fasting stage. Finally, an ultrasound assessment was carried out in randomly selected 56 study participants. RESULTS: PCOS women reported more prominent knee-related symptoms (p = 0.035) and more impaired activities of daily living (ADL) (p = 0.001) than controls. Cartilage thickness of the left and right medial condyle and left lateral condyle was significantly greater in PCOS group (n = 41) than in control group (n = 15) (p = 0.05, p = 0.006, and p = 0.036, respectively). COMP correlated significantly and negatively with testosterone levels (p = 0.029, r = - 0.297) in women with PCOS and the correlation remained significant after controlling for BMI. CONCLUSIONS: Women with PCOS may experience knee-related symptoms and impaired ADL. They had greater knee femoral cartilage thickness. Although sCOMP levels did not significantly differ between the groups, lower levels of sCOMP may be inherent to PCOS patients with higher testosterone levels. Key Points • Although PCOS patients may experience more prominent knee related symptoms, their femoral cartilage of the knee joint is found thicker than controls. • PCOS patients did not have significantly elevated levels of sCOMP. • Lower sCOMP levels were related to higher testosterone levels.

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.

Inositols in PCOS.

(1) Background: Myoinositol (MI) and D-chiro-inositol (DCI) are involved in a number of biochemical pathways within oocytes having a role in oocyte maturation, fertilization, implantation, and post-implantation development. Both inositols have a role in insulin signaling and hormonal synthesis in the ovaries. (2) Methods: Literature search (with key words: inositols, myo-inositol, d-chiro-inositol, PCOS) was done in PubMed until Sept. 2020 and 197 articles were identified, of which 47 were of clinical trials (35 randomized controlled trials). (3) Results: Many studies have demonstrated that in patients with polycystic ovarian syndrome (PCOS) MI treatment improved ovarian function and fertility, decreased the severity of hyperandrogenism including acne and hirsutism, positively affected metabolic aspects, and modulated various hormonal parameters deeply involved in the reproductive axis function and ovulation. Thus treating with MI has become a novel method to ameliorate PCOS symptoms, improve spontaneous ovulation, or induce ovulation. The current review is focused on the effects of MI and DCI alone or in combination with other agents on the pathological features of PCOS with focus on insulin resistance and adverse metabolic outcomes. (4) Conclusions: The available clinical data suggest that MI, DCI, and their combination in physiological ratio 40:1 with or without other compound could be beneficial for improving metabolic, hormonal, and reproductive aspects of PCOS.

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.

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.

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.