Assessment of the Diagnostic Utility of Serum Omentin 1 and IL-6 in Early Stages of Diabetic Nephropathy.

In India, diabetic nephropathy (DN) is the most common cause of chronic kidney disease. Timely detection of microalbuminuria and appropriate intervention can reverse or arrest the progress of nephropathy. The pathogenesis of diabetic nephropathy has revealed that during the early onset of kidney involvement in diabetics, inflammation and fibrosis progress from tubular to glomerular damage. This study was designed to elucidate the association of chemokines, Omentin 1, and interleukin 6 (IL-6) with microalbuminuria. MATERIAL: Settings and Design: This cross-sectional observational study was conducted as a collaborated study in the Departments of General Medicine and Biochemistry, All India Institute of Medical Sciences, Bhubaneswar, India, during 2019-2020. METHODS AND MATERIAL: Our study group comprised 116 diabetes mellitus patients. They were grouped into two, each of 58 on the basis of their urine albumin levels; Group 1 (controls) had UACR < 30 µg/mg, eGFR> 90ml/ min and Group 2 (cases) had UACR ≥ 30 µg/mg and < 300 µg/mg, eGFR>60ml/min and < 90ml/min. Serum omentin 1 and IL-6, creatinine, glycated haemoglobin (HbA1c), fasting (FBS) and postprandial blood sugar (PPBS), lipid profile, total protein, albumin, and fasting insulin, HOMA-IR were studied. OBSERVATION: Our study showed that Omentin 1 levels were decreased, and IL-6 levels were increased in the DN group compared to the T2DM without DN. The risk estimates calculated revealed that diabetes mellitus patients having an IL-6: omentin ratio ≥ 0.26 had Odds of 3.97 of developing DN, which was statistically significant (CI 2.36-6.68). Therefore, a ratio of ≤ 0.26 was found to be kidney protective among diabetes mellitus patients. CONCLUSION: From the results of this present study, we recommend that estimation of serum IL-6: omentin 1 ratio of T2DM will aid in identifying early stages of DN before the onset of microalbuminuria.

Assessment of heart rate variability (HRV) in subjects with type 2 diabetes mellitus with and without diabetic foot: correlations with endothelial dysfunction indices and markers of adipo-inflammatory dysfunction.

BACKGROUND: Some studies have suggested that patients with diabetes and foot complications have worse cardiovascular and cerebrovascular risk profiles, higher degrees of endothelial dysfunction and arterial stiffness and a higher inflammatory background than patients with diabetes without diabetic foot complications. Patients with diabetes mellitus have an alteration in the sympathovagal balance as assessed by means of heart rate variability (HRV) analysis, which is also related to the presence of endothelial dysfunction. Other studies suggest a possible role of inflammation coexisting with the alteration in the sympathovagal balance in favor of the atherosclerotic process in a mixed population of healthy subjects of middle and advanced age. AIMS: The aim of this study was to evaluate the degree of alteration of sympathovagal balance, assessed by HRV analysis, in a cohort of patients with diabetes mellitus with diabetic foot and in control subjects without diabetic foot compared with a population of healthy subjects and the possible correlation of HRV parameters with inflammatory markers and endothelial dysfunction indices. METHODS: We enrolled all patients with diabetic ulcerative lesions of the lower limb in the Internal Medicine with Stroke Care ward and of the diabetic foot outpatient clinic of P. Giaccone University Hospital of Palermo between September 2019 and July 2020. 4-h ECG Holter was performed. The following time domain HRV measures were analyzed: average heart rate, square root of the mean of successive differences of NN (RMSSD), standard deviation or square root of the variance (SD), and standard deviation of the means of the NN intervals calculated over a five-minute period (SDANN/5 min). The LF/HF ratio was calculated, reactive hyperemia was evaluated by endo-PAT, and serum levels of vaspine and omentin-1 were assessed by blood sample collection. RESULTS: 63 patients with diabetic foot, 30 patients with diabetes and without ulcerative complications and 30 patients without diabetes were enrolled. Patients with diabetic ulcers showed lower mean diastolic blood pressure values than healthy controls, lower MMSE scores corrected for age, lower serum levels of omentin-1, lower RHI values, higher body weight values and comparable body height values, HF% and LF/HF ratio values. We also reported a negative correlation between the RHI value and HRV indices and the expression of increased parasympathetic activity (RMSDD and HF%) in subjects with diabetic foot and a statistically significant positive correlation with the LF/HF ratio and the expression of the sympathovagal balance. DISCUSSION: Patients with diabetic foot show a higher degree of activation of the parasympathetic system, expressed by the increase in HF values, and a lower LF/HF ratio. Our findings may corroborate the issue that a parasympathetic dysfunction may have a possible additive role in the pathogenesis of other vascular complications in subjects with diabetic foot.

Assessment of serum chemerin, vaspin and omentin-1 levels in patients with polycystic ovary syndrome.

OBJECTIVE: To determine serum chemerin, vaspin and omentin-1 in overweight and normal weight patients with polycystic ovary syndrome (PCOS) and investigate the possible relationship between these adipokines and metabolic syndrome. METHODS: This cross sectional study enrolled women with PCOS and healthy women. Serum chemerin, vaspin and omentin-1 were assessed by enzyme-linked immunosorbent assay methods. RESULTS: Forty patients with PCOS and 30 healthy controls were included in the study. In the PCOS group, 18 women were overweight (body mass index [BMI] = 25.0-29.9 kg/m(2)) and 22 had normal weight (BMI = 18.5-24.9 kg/m(2)). Chemerin, total cholesterol, dehydroepiandrosterone sulphate and free androgen index (FAI) were significantly higher; and high-density lipoprotein cholesterol and sex hormone binding globulin were significantly lower in overweight PCOS patients compared with normal weight PCOS patients. A positive correlation was found between chemerin and BMI, triglyceride, insulin, homeostatic model assessment of insulin resistance and FAI in the PCOS group. There was no difference in serum chemerin, vaspin and omentin-1 between PCOS patients and healthy controls. CONCLUSION: Circulating chemerin was increased in overweight compared with normal weight PCOS patients. The most predictive variables for circulating chemerin in PCOS patients were BMI, FAI and age.

Assessment of Serum Concentrations of Ghrelin, Obestatin, Omentin-1, and Apelin in Children with Type 1 Diabetes.

The increasing knowledge on the functions of gastric peptides and adipokines in the body allows the assumption of their major role linking the process of food intake, nutritional status, and body growth, largely through the regulation of glucose metabolism and insulin resistance. The aim of the study was the assessment of serum levels of selected gastric peptides and adipocytokines in children with type 1 diabetes, with respect to the disease duration. The study involved 80 children aged 4-18 years (M/F -37/43). Children with type 1 diabetes (n = 46) were compared to the control group (n = 34). The study group was divided into 4 subgroups: (I) patients with newly diagnosed type 1 diabetes, after an episode of ketoacidosis (n = 10), (II) patients with type 1 diabetes of duration no longer than 5 years (n = 9), (III) patients with 5 to 10 years of DT1 (n = 20), and (IV) patients with type 1 diabetes of duration longer than 10 years (n = 7). The concentrations of gastric peptide and adipocytokines across all subgroups were lower than in the control group. The differences were statistically significant (p < 0.0001), which may be of importance in the development of the disease complications.

Assessment of human cartilage glycoprotein 39 (YKL-40), preptin, and nitric oxide in adolescent patients with type 1 diabetes and its relation to cardiorenal affection.

AIM: To evaluate new biomarkers such as YKL-40, preptin, and nitric oxide (NO) in patients with diabetes and to assess its relation to cardiorenal injury. PATIENTS AND METHODS: The study included 62 patients with type 1 diabetes and 30 healthy volunteers. Blood sample was taken for assessment of glycosylated hemoglobin, lipid profile, YKL-40, preptin, and NO. Also, urine sample was taken for analysis of albumin/creatinine ratio. Echocardiography was also done. RESULTS: NO was lower, whereas YKL-40, preptin, and albumin/creatinine ratio were significantly higher in patients with diabetes. NO had a significant negative correlation with LVEDD, LVESD, PWT, LV mass, YKL-40, preptin, and albumin/creatinine ratio. YKL-40 had a significant positive correlation with waist/height ratio, preptin and negative correlation with E/A ratio. Stepwise multiple regression revealed that E/A ratio is the only parameter related to YKL-40. On the contrary, NO and systolic blood pressure are related to preptin. CONCLUSION: A significant reduction of NO and elevation of YKL-40 and preptin was found in patients with diabetes. A decrease in NO is associated with diastolic dysfunction, LV hypertrophy, and renal impairment, whereas YKL-40 is associated with diastolic dysfunction. An increase in preptin level was associated with hypertension.

Serum YKL-40 in risk assessment for colorectal cancer: a prospective study of 4,496 subjects at risk of colorectal cancer.

The aim of the present study was to test the hypothesis that high serum YKL-40 associates with colorectal cancer in subjects at risk of colorectal cancer. We measured serum YKL-40 in a prospective study of 4,496 Danish subjects [2,064 men, 2,432 women, median age 61 years (range, 18-97)] referred to endoscopy due to symptoms or other risk factors for colorectal cancer. Blood samples were collected just before large bowel endoscopy. Serum YKL-40 was determined by ELISA. Serum YKL-40 was higher (P < 0.0001, unadjusted for confounding covariates) in subjects diagnosed with colon cancer (median 126 µg/L, 25%-75%: 80-206 µg/L) and rectal cancer (104, 72-204 µg/L) compared with subjects with adenoma (84, 53-154 µg/L), other nonmalignant findings (79, 49-138 µg/L), and no findings (62, 41-109 µg/L). Serum YKL-40 independently predicted colorectal cancer [OR, 1.53; 95% confidence interval (CI), 1.40-1.67; AUC = 0.68, P < 0.0001]. Restricting the analysis to subjects with no comorbidity increased the OR for serum YKL-40 to predict colorectal cancer (OR, 1.82; 1.58-2.08; AUC = 0.73, P < 0.0001). Combining serum YKL-40 and CEA demonstrated that both were significant [(YKL-40, OR, 1.27; 95% CI, 1.16-1.40); (CEA, OR, 1.92; 1.75-2.10; AUC = 0.75, P < 0.0001; OR for a 2-fold difference in marker level)]. Multivariable analysis (YKL-40, CEA, age, gender, body mass index, and center) showed that serum YKL-40 was a predictor for colorectal cancer in individuals without comorbidity (OR, 1.25; 95% CI, 1.05-1.40; P = 0.012), whereas this was not the case for those with comorbidity (OR, 0.98; 95% CI, 0.84-1.14; P = 0.80). In conclusion, high serum YKL-40 in subjects suspected of colorectal cancer and without comorbidity associates with colorectal cancer. Determination of serum YKL-40 may be useful in combination with other biomarkers in risk assessment for colorectal cancer. Cancer Epidemiol Biomarkers Prev; 24(3); 621-6. ©2015 AACR.

The prediction role of indexes of circulating adipokines for common anthropometric and nutritional characteristics of obesity in the obese Central European population.

AIMS: This study was designed to investigate the relationship between 8 selected adipokines (leptin, leptin receptor, adiponectin, agouti-related peptide, omentin, visfatin, adipsin and resistin), dietary composition and anthropometric parameters found in the Central European obese population. METHODS: A total of 65 unrelated obese Central European Caucasian individuals were recruited for the study. Phenotypic measurements included weight, height, BMI, lean body mass, fat mass, body fat, waist and hip circumference, waist-hip ratio (WHR) and skinfold thickness. Participants completed standardized self-reported 7-day food records. Plasma levels of leptin, leptin receptor, adiponectin, agouti-related peptide (AgRP), resistin, adipsin, omentin and visfatin were examined using ELISA. RESULTS: Multiple associations (weight, height, percentage of body fat, waist circumference, hip circumference, WHR and sum of skinfold thickness) with the circulation levels of the investigated adipokines were identified. Leptin-Leptin receptor (L-LR) levels were found to correlate with total energy intake and macronutrients while adipsin was found to strongly correlate with multiple adipokines. Furthermore, the L-LR index was found to constitute a more accurate description of the relationship between BMI and body weight than individual measurements and the Ag-LR index was found to strongly correlate with both anthropometric and dietary characteristics. CONCLUSION: Following confirmation on larger population samples and on samples of different ethnicities, the reported adipokine indexes could become a useful tool for estimating nutritional status and predicting the body composition of specific patient groups.

A repertoire of biomarkers helps in detection and assessment of therapeutic response in epithelial ovarian cancer.

In epithelial ovarian cancer (EOC), the cancer antigen 125 (CA-125) has been conventionally used to help in diagnosis and assessment of response to treatment. Currently, YKL-40 (Tyrosine-Lysine-Leucine-40) and circulating cell-free DNA are being evaluated for possession of similar ability. In this study, we aimed to assess the ability of a repertoire of potential biomarkers in detecting and assessing therapeutic response, in advanced EOC. Blood levels of CA-125, YKL-40, total cell-free DNA (CFDNA), cell-free nuclear DNA (CFnDNA), and cell-free mitochondrial DNA (CFmDNA) levels were measured in 100 untreated patients of advanced EOC from November 2009 to June 2011, and again on treatment completion from the 20 patients who appeared for follow-up analysis. Significantly, higher proportion of untreated patients had serum CA-125 >3 times upper limit of normal (ULN) (90.0%; P < 0.0001) and plasma YKL-40 >ULN (77.0%; P < 0.0001), both of which significantly decreased, Posttherapy. posttherapy, CFDNA (P < 0.0001), and CFnDNA (P < 0.0001) levels significantly decreased as compared to pretreatment levels. Positive and significant correlations existed between pretherapy CFDNA and CFnDNA [Spearman rho (ρ) = 1.000; P < 0.0001], and also with CFmDNA (ρ = 0.301; P = 0.002), separately between CFnDNA and CFmDNA (ρ = 0.303; P = 0.002), as well as between plasma YKL-40 and patient age (ρ = 0.353; (P < 0.0001). On treatment completion, CFDNA and CFnDNA levels showed positive and significant correlation (ρ = 1.000; P < 0.0001). Therefore serum CA-125 and plasma YKL-40 aid detection and assessment of therapeutic response, in advanced EOC. CFDNA and CFnDNA help in estimating extent of therapeutic response in advanced EOC.

Validation of terminal peptide of procollagen III for the detection and assessment of nonalcoholic steatohepatitis in patients with nonalcoholic fatty liver disease.

UNLABELLED: Liver biopsy is the reference standard for the detection of nonalcoholic steatohepatitis (NASH) within nonalcoholic fatty liver disease (NAFLD). The aim of this study was to identify a biomarker of NASH in patients without significant fibrosis. In all, 172 patients from two centers with biopsy-proven NAFLD were included in this study. Eighty-four patients from a single center were included as a derivation cohort and 88 patients from a second center were included as a validation cohort. Serum samples were tested for candidate markers of fibrosis and inflammation alongside hematological and biochemical markers. Among patients without advanced fibrosis, terminal peptide of procollagen III (PIIINP) was the only marker found to be associated with a histological diagnosis of NASH in both cohorts. PIIINP also correlated with the total NAFLD activity score (NAS) and its constituent components (P < 0.001). Area under receiver operating characteristic curve (AUROC) for PIIINP in discriminating between NASH and simple steatosis (SS) was 0.77-0.82 in patients with F0-2 fibrosis and 0.82-0.84 in patients with F0-3 fibrosis. PIIINP was elevated in patients with advanced fibrosis, the overwhelming majority of whom had NASH. When incorporating patients with all degrees of fibrosis from both cohorts, PIIINP was able to discriminate between patients with SS and those with NASH or advanced fibrosis with AUROC 0.85-0.87. CONCLUSION: PIIINP discriminates between SS and NASH or advanced fibrosis. The use of a single biomarker in this context will be of clinical utility in detecting the minority of patients with NAFLD who have NASH or advanced fibrosis related to NASH.

The functional polymorphism Ala258Ser in the innate receptor gene ficolin-2 in the donor predicts improved renal transplant outcome.

BACKGROUND: Innate immunity plays a role in controlling adaptive immune responses. METHODS: We investigated the clinical relevance of single nucleotide polymorphisms in 22 genes encoding innate, secreted, and signaling pattern recognition receptors in a total of 520 donor-recipient pairs of postmortem, human leukocyte antigen-DR-compatible kidney transplantations. Associations with rejection incidence were tested in an a priori randomized training set and validation set. RESULTS: Polymorphisms in TLR-3 (rs3775296) in the recipients and in ficolin-2 (rs7851696; Ala258Ser) and C1qR1 (rs7492) in the donors showed the strongest association with severe rejection. In multivariate analysis, presence of the ficolin-2 Ala258Ser variant in the donor predicted lower incidence of severe rejection (odds ratio=0.3; 95% confidence interval, 0.1-0.9; P=0.024) and of graft loss (hazard ratio=0.5; 95% confidence interval, 0.2-1.0; P=0.046) independently of clinical risk factors. Ficolin-2 messenger RNA expression was detected in pretransplantation biopsies from 69 donor grafts. Serum and tissue ficolin-2 levels were unaffected by genotype. Ficolin-2 protein, which bound to dying cells, was detected in donor kidneys in a passenger leukocyte-like pattern. Indeed, monocytes, monocyte-derived macrophages, and peripheral blood mononuclear cells expressed ficolin-2. Donor grafts with the ficolin-2 Ala258Ser variant contained significantly elevated expression of interleukin 6, having ascribed cytoprotective effects. It has been described that Ala258Ser leads to increased binding capacity of ficolin-2 to N-acetylglucosamine. CONCLUSIONS: Presence of the ficolin-2 Ala258Ser polymorphism in the donor independently predicts improved graft outcome. Based on mechanistic data, we propose that this functional polymorphism leads to more efficient handling of injured cells by phagocytozing cells, resulting in decreased intragraft exposure to danger signals and dampened alloimmune responses.

Comparison of LecT-Hepa and FibroScan for assessment of liver fibrosis in hepatitis B virus infected patients with different ALT levels.

BACKGROUND: FibroScan is one of the noninvasive techniques based on the transient elastography that can assess the progression of liver fibrosis in chronic hepatitis patients in daily clinical practice. Recently, LecT-Hepa was validated as a serological glycomarker correlating well with the fibrosis stage determined by liver biopsy, and was superior to many other noninvasive biochemical markers and tests. We compared the reliability of LecT-Hepa with that of FibroScan for evaluation of liver fibrosis. METHODS: The effects of increased alanine aminotransferase (ALT) activities on LecT-Hepa and FibroScan were investigated. RESULTS: The areas under the receiver-operating characteristic curves, sensitivity and specificity for detecting cirrhosis, which is one of the outcomes of fibrosis estimation, were 0.82, 72.5% and 78.2% of LecT-Hepa, 0.85, 87.0% and 74.1% of FibroScan; these did not differ significantly. The count distribution of LecT-Hepa in non-cirrhosis group or cirrhosis group did not differ between the patients grouped according to their ALT levels, whereas that of FibroScan was substantially affected. CONCLUSION: LecT-Hepa was confirmed as a reliable noninvasive test for the evaluation of liver fibrosis in hepatitis B virus-infected patients with comparable performance to that of FibroScan and proved to be unaffected by inflammation.

Identification and assessment of new biomarkers for colorectal cancer with serum N-glycan profiling.

BACKGROUND: The objectives of this study were to identify and validate the diagnostic value of N-glycan markers in colorectal cancer (CRC) and to uncover their underlying molecular mechanism. METHODS: In total, 347 individuals, including patients with CRC, patients with colorectal adenoma, and healthy controls, were divided randomly into a training group (n = 287) and retrospective validation groups (n = 60). Serum N-glycan profiling was analyzed by DNA sequencer-assisted/flurophore-assisted carbohydrate electrophoresis (DSA-FACE). Two diagnostic models were constructed based on N-glycan profiling with logistic stepwise regression. The diagnostic performance of each model was assessed further in retrospective, prospective (n = 43), and follow-up (n = 46) cohorts. Lectin blot and reverse transcriptase-polymerase chain reaction were used to analyze the total core-fucosylated residues and molecular expression involved in core-fucosylation modifications in CRC. RESULTS: Two diagnostic models designated CRCglycoA and CRCglycoB were constructed to differentiate CRC from normal and adenoma, respectively. The areas under the receiver operating characteristic curves (AUC) of both CRCglycoA and CRCglycoB were higher than the AUC of carcinoembryonic antigen (CEA) (CRCglycoA, 0.92 vs 0.81; CRCglycoB, 0.81 vs 0.73). The sensitivity and accuracy of CRCglycoA improved from 21.7% to 25% and from 11.63% to 18% in the training cohort, the retrospective cohort, and the prospective cohorts compared with the sensitivity and accuracy of CEA. The sensitivity of CRCglycoB improved from 20% to 28.23%. Both altered N-glycans, and results from the diagnostic models were reversed after curative surgery. The level of total core fucose residues and fucosyltransferase were decreased significantly in CRC. CONCLUSIONS: The current results indicated that the N-glycan markers based diagnostic models are new, valuable, noninvasive alternatives for identifying CRC. The authors concluded that decreased fucosyltransferase may be responsible for decreased levels of total core-fucosylated modification in both tissues and serum from patients with CRC.