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.

Prediabetes is Characterized by Higher FGF23 Levels and Higher Prevalence of Vitamin D Deficiency Compared to Normal Glucose Tolerance Subjects.

In the last years there is an increasing interest towards the bone as an endocrine organ and the role of bone and calcium-phosphate metabolism markers in a range of metabolic disturbances. The aim of the present study is to assess the changes of calcium phosphate metabolism markers in patients with prediabetes compared to normogycemic controls and their link to glucose disturbances and cardiovascular risk factors. In this study, 80 patients with mean age 50.4±10.6 years were included, divided into 2 age- and BMI-matched groups - group 1 with obesity without glycemic disturbances (n=41) and group 2 with obesity and prediabetes (n=39). Oral glucose tolerance test (OGTT) with measurement of immunoreactive insulin was performed in all participants and levels of PTH, 25(OH)D, FGF23, and Klotho were measured. We found significantly higher levels of FGF23 in patients with prediabetes compared to normal glucose tolerance subjects (10.4±10.7 vs. 5.8±7.3 pg/ml; p=0.03). FGF23 showed a weak positive correlation to fasting blood glucose (r=0.224; p=0.048) but not to blood glucose on the first and second hour of oral glucose tolerance test or insulin levels. There was extremely high prevalence of vitamin D deficiency in both groups. Lower levels of 25(OH)D were observed in prediabetes group, although without statistical significance (p=0.57). Patients with prediabetes have higher FGF23 levels and higher prevalence of vitamin D deficiency compared to normal glucose tolerance subjects. Elevated FGF23 levels seem to be correlated more to elevated fasting blood glucose levels than to insulin resistance state of the patients.

Irisin and Testosterone in Men with Metabolic Syndrome.

The beneficial effects of testosterone on the metabolism and body composition of men are well established but the exact mechanisms of these effects are not clearly understood. A potential explanation might lie in the hormones, secreted from skeletal muscles, named "myokines". One such myokine, irisin, has been shown to also have potential beneficial metabolic effects. The aim of this pilot study was to evaluate the association of serum testosterone with circulating serum irisin levels in men with metabolic syndrome. A total 128 men with metabolic syndrome (MS) based on the IDF criteria participated in the study. Irisin serum concentration was determined by means of ELISA. Mean age±SD of the study participants was 51.8±8.3 years. Seventy percent of the subjects had type 2 diabetes mellitus. Circulating irisin was inversely associated with serum testosterone (r=-0.279, p<0.01) and was significantly higher in subjects with hypogonadism - mean±SD 252.0±147.1 vs.172.9±92.2 ng/ml (p=0.002). ROC analysis of serum irisin value was determined for distinguishing subjects with hypogonadism (AUC=0.670). In a multiple linear regression model with BMI, FPG, age, and irisin, only BMI (ß=-0.228, p=0.004) and irisin (ß=-0.170, p=0.045) were variables independently associated with testosterone concentrations. Irisin is negatively associated with serum testosterone in our population sample of men with MS. This might suggest a possible involvement of myokines and testosterone with regards to the human metabolism. As no such data on this association has been reported in the literature thus far, further prospective studies are required to elucidate this correlation.

A comparison of the clinical usefulness of neck circumference and waist circumference in individuals with severe obesity.

Purpose/Aim: Neck circumference (NC) is an emerging anthropometric parameter that has been proposed to reflect metabolic health. The aim of the current study was to compare its clinical usefulness to waist circumference (WC) in the assessment of individuals with severe obesity. MATERIALS AND METHODS: A total of 255 subjects participated in the study. All anthropometric measurements were done by a single medical professional. Biochemical measurements included oral glucose-tolerance tests (OGTTs), fasting insulin, lipids, and hepatic enzymes. RESULTS: The mean age of the participants was 49 ± 12 years with the mean body mass index (BMI) of 36.9 ± 6.2 kg/m2. Correlation analyses revealed that while WC was better associated with adiposity parameters, it was of little use in comparison to NC with regard to metabolic outcomes. In men, NC was positively associated with fasting plasma glucose, fasting insulin, FINDRISC scores. ROC analyses showed NC was better in distinguishing type 2 diabetes (AUC = 0.758; p < 0.001), insulin resistance (AUC = 0.757; p = 0.001), metabolic syndrome (AUC = 0.724; p < 0.001), and hypertension (AUC = 0.763; p = 0.001). Similar correlations were observed in women. Using binary logistic regression, we determined that a NC of ≥35 cm in women and ≥38 cm in men are valuable cut-off values to use in the everyday practice. CONCLUSION: In individuals with severe obesity, NC performs better than WC in the assessment of metabolic health.

Myostatin and carbohydrate disturbances.

Purpose/aim of the study: Myostatin is a myokine that has been shown to inhibit muscle growth and to have potentially deleterious effects on metabolism. The aim of the current study was to compare its circulating serum levels in subjects from the whole spectrum of carbohydrate disturbances leading to diabetes. MATERIALS AND METHODS: A total of 159 age-, sex-, and BMI-matched subjects participated in the study - 50 had normal glucose tolerance (NGT), 60 had prediabetes (PreDM), and 49 had type 2 diabetes mellitus (T2D). Oral glucose tolerance testing was used to determine glucose tolerance. Serum myostatin was quantified by means of ELISA. RESULTS: Circulating serum myostatin levels were highest in patients with T2D, lower in subjects with prediabetes, and lowest in subjects with normoglycemia (all p < 0.05). Myostatin was shown to be positively associated with fasting plasma glucose, HOMA-IR, hepatic enzymes, uric acid, and FINDRISC questionnaire scores in both sexes. ROC analyses determined circulating myostatin levels to be of value for differentiating subjects with T2D (AUC = 0.72, p = 0.002 in men; AUC = 0.70, p = 0.004 in women) in the study population. After adjustment for potential confounders, in a multiple binary logistic regression model, serum myostatin added further information to traditional risk estimates in distinguishing subjects with T2D. CONCLUSIONS: Serum myostatin levels are higher with deterioration of carbohydrate tolerance. Furthermore, circulating myostatin is positively associated with traditional biochemical estimates of poor metabolic health. These data add to evidence of the involvement of this myokine in the pathogenesis of T2D.

Increased kallistatin levels in patients with obesity and prediabetes compared to normal glucose tolerance.

PURPOSE: Kallistatin is a member of serine protease inhibitors (SERPIN) family, which has various functions such as regulation of cardiovascular function and blood vessels development. Its levels are elevated in patients with type 1 and type 2 diabetes with chronic diabetic complications. The aim of the present study was to compare serum kallistatin levels between obese subjects with prediabetes and with normal glucose tolerance. METHODS: In this study we included 80 subjects at mean age of 50.4 ± 10.6 years, divided into two age and BMI-matched groups - group 1 with obesity without glycemic disturbances (n = 41) and group 2 with obesity and prediabetes (n = 39). Oral glucose tolerance test with measurement of immunoreactive insulin was performed in all participants and levels of kallistatin were measured using ELISA method. RESULTS: We found significantly higher levels of kallistatin in patients with prediabetes compared to controls (data are presented as median (min; max) because data were not normally distributed) (6.3 (4.4; 9.0) vs. 5.6 (3.1; 8.7) ng/ml; p = 0.022) and in patients with metabolic syndrome compared to those without (6.0 (4.9; 9.0) vs. 5.5 (3.1; 7.7); p = 0.006), but the levels were similar in patients with and without insulin resistance. CONCLUSIONS: The levels of kallistatin are higher in individuals with prediabetes, but are similar in subjects with and without insulin resistance, which indicates that the main factor for its increased levels may be hyperglycemia and not insulin sensitivity state.

Increased peroxiredoxin 4 levels in patients with prediabetes compared to normal glucose tolerance subjects.

BACKGROUND: Peroxiredoxin 4 is a part of endogen antioxidant system and its levels are elevated in oxidative stress conditions. Its levels are positively associated with cardiovascular risk. The aim of this study was to compare serum peroxiredoxin 4 levels between obese subjects with prediabetes and with normal glucose tolerance. METHODS: In this study, we included 80 patients with mean age 50·4 ± 10·6 years and divided them into two age and BMI-matched groups - group 1 with obesity without glycaemic disturbances (n = 41) and group 2 with obesity and prediabetes (n = 39). Oral glucose tolerance test with measurement of immunoreactive insulin was performed in all participants, and the levels of peroxiredoxin 4 were measured using ELISA method. RESULTS: We found significantly higher levels of peroxiredoxin 4 in patients with prediabetes compared to controls (2851·2 ± 4576·6 pg/ml vs 1088·0 ± 753·3 pg/ml; P = 0·022). There was a mild but statistically significant correlation between peroxiredoxin 4 and weight (r = 0·232; P = 0·038), waist circumference (r = 0·239; P = 0·044), creatinine (r = 0·264; P = 0·019), liver enzymes (ASAT - r = 0·289; P = 0·019 and ALAT - r = 0·305; P = 0·07) and white blood cells count (r = 0·317; P = 0·005). There was no difference in peroxiredoxin 4 levels in patients with and without insulin resistance, as well as with and without metabolic syndrome (MetS), although the levels of peroxiredoxin 4 increased with the number of components of MetS. CONCLUSIONS: The levels of peroxiredoxin 4 are higher in patients with prediabetes, but are similar in subjects with and without insulin resistance, which suggests that the main factor for its increased levels is hyperglycaemia and not insulin sensitivity state.

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.

Acne vulgaris is associated with intensive pubertal development and altitude of residence--a cross-sectional population-based study on 6,200 boys.

UNLABELLED: Acne vulgaris is a chronic inflammatory disease with a complex pathogenesis that affects predominantly adolescents. The aim of the study was to investigate the interrelations between the presence of acne and several variables associated with somatic growth, pubertal maturation, and environmental conditions (altitude and regions of residence). A population sample of 6,200 clinically healthy boys (0-19 years) was examined and the presence of acne was determined. Height, weight, testicular volumes, penile length and circumference, as well as pubic hair were also measured. The prevalence of moderate and severe acne in the whole group was 7.74 %, while in the age group 12-19 years, it was 19.31 %. Twelve-15-year-old boys with acne were taller and heavier than the ones without. They also had increased penile length and circumference as well as larger testicular volumes. Somatometric and pubertal characteristics of 17-19-year-old boys with and without acne were similar. The prevalence of the disease did not differ between the rural and urban inhabitants. However, the acne frequency decreased with the increasing of the altitude where the boys lived. CONCLUSIONS: Our results showed that the development of acne vulgaris in male adolescents was associated with an intensive growth and pubertal maturation, while obesity per se did not play an important role. Of particular interest was the association between the prevalence of acne and the altitude of residence.

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.

Islet transplantation-immunological challenges and current perspectives.

Pancreatic islet transplantation is a minimally invasive procedure aiming to reverse the effects of insulin deficiency in patients with type 1 diabetes (T1D) by transplanting pancreatic beta cells. Overall, pancreatic islet transplantation has improved to a great extent, and cellular replacement will likely become the mainstay treatment. We review pancreatic islet transplantation as a treatment for T1D and the immunological challenges faced. Published data demonstrated that the time for islet cell transfusion varied between 2 and 10 h. Approximately 54% of the patients gained insulin independence at the end of the first year, while only 20% remained insulin-free at the end of the second year. Eventually, most transplanted patients return to using some form of exogenous insulin within a few years after the transplantation, which imposed the need to improve immunological factors before transplantation. We also discuss the immunosuppressive regimens, apoptotic donor lymphocytes, anti-TIM-1 antibodies, mixed chimerism-based tolerance induction, induction of antigen-specific tolerance utilizing ethylene carbodiimide-fixed splenocytes, pretransplant infusions of donor apoptotic cells, B cell depletion, preconditioning of isolated islets, inducing local immunotolerance, cell encapsulation and immunoisolation, using of biomaterials, immunomodulatory cells, etc.

Long-term effectiveness, outcomes and complications of bariatric surgery.

Dietary imbalance and overeating can lead to an increasingly widespread disease - obesity. Aesthetic considerations aside, obesity is defined as an excess of adipose tissue that can lead to serious health problems and can predispose to a number of pathological changes and clinical diseases, including diabetes; hypertension; atherosclerosis; coronary artery disease and stroke; obstructive sleep apnea; depression; weight-related arthropathies and endometrial and breast cancer. A body weight 20% above ideal for age, gender and height is a severe health risk. Bariatric surgery is a set of surgical methods to treat morbid obesity when other treatments such as diet, increased physical activity, behavioral changes and drugs have failed. The two most common procedures currently used are sleeve gastrectomy and gastric bypass. This procedure has gained popularity recently and is generally considered safe and effective. Although current data show that perioperative mortality is low and better control of comorbidities and short-term complications is achieved, more randomized trials are needed to evaluate the long-term outcomes of bariatric procedures. This review aims to synthesize and summarize the growing evidence on the long-term effectiveness, outcomes and complications of bariatric surgery.

Stress Hyperglycemia, Diabetes Mellitus and COVID-19 Infection: Risk Factors, Clinical Outcomes and Post-Discharge Implications.

The novel severe acute respiratory distress syndrome-coronavirus 2 (SARS-CoV-2) has caused one of the most substantial pandemics that has affected humanity in the last century. At the time of the preparation of this review, it has caused the death of around 5 million people around the globe. There is ample evidence linking higher mortality risk rates from Coronavirus disease-19 (COVID-19) with male gender, advancing age and comorbidities, such as obesity, arterial hypertension, cardiovascular disease, chronic obstructive pulmonary disease, diabetes mellitus, and cancer. Hyperglycemia has been found to be accompanying COVID-19 not only in individuals with overt diabetes. Many authors claim that blood glucose levels should also be monitored in non-diabetic patients; moreover, it has been confirmed that hyperglycemia worsens the prognosis even without pre-existing diabetes. The pathophysiological mechanisms behind this phenomenon are complex, remain controversial, and are poorly understood. Hyperglycemia in the setting of COVID-19 could be a consequence of deterioration in pre-existing diabetes, new-onset diabetes, stress-induced or iatrogenic due to substantial usage of corticosteroids within the context of a severe COVID-19 infection. It is also plausible that it might be a result of adipose tissue dysfunction and insulin resistance. Last but not least, SARS-CoV-2 is also claimed to trigger sporadically direct ß-cell destruction and ß-cell autoimmunity. Pending further validations with longitudinal data are needed to legitimize COVID-19 as a potential risk factor for the development of diabetes. Hereby, we present an emphasized critical review of the available clinical data in an attempt to unravel the complex mechanisms behind hyperglycemia in COVID-19 infection. The secondary endpoint was to evaluate the bidirectional relationship between COVID-19 and diabetes mellitus. As the worldwide pandemic is still expanding, demand for answering these questions is arising. It will be of immense help for the management of COVID-19 patients, as well as for the implementation of post-discharge policies for patients with a high risk of developing 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.

Targeting Inflammatory Cytokines to Improve Type 2 Diabetes Control.

Type 2 diabetes (T2D) is one of the most common chronic metabolic disorders in adulthood worldwide, whose pathophysiology includes an abnormal immune response accompanied by cytokine dysregulation and inflammation. As the T2D-related inflammation and its progression were associated with the balance between pro and anti-inflammatory cytokines, anticytokine treatments might represent an additional therapeutic option for T2D patients. This review focuses on existing evidence for antihyperglycemic properties of disease-modifying antirheumatic drugs (DMARDs) and anticytokine agents (anti-TNF-α, anti-interleukin-(IL-) 6, -IL-1, -IL-17, -IL-23, etc.). Emphasis is placed on their molecular mechanisms and on the biological rationale for clinical use. Finally, we briefly summarize the results from experimental model studies and promising clinical trials about the potential of anticytokine therapies in T2D, discussing the effects of these drugs on systemic and islet inflammation, beta-cell function, insulin secretion, and insulin sensitivity.

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.