Search

Objective The adipokine asprosin, which was recently discovered, facilitates hepatic glucose production. The aim of this study is to see whether serum asprosin concentrations are linked to diabetic nephropathy (DN). Methods We performed this investigation in a group of 212 type 2 diabetes (T2DM) patients. These patients were classified into three subgroups: DN0 group (normal to mildly increased), DN1 group (moderately increased), and DN2 group (severely increased) on the basis of urine albumin-to-creatinine ratio (ACR). Results When compared to the controls, T2DM patients had higher serum asprosin levels. The DN2 group had significantly higher serum asprosin than the DN0 and DN1 groups. Furthermore, the DN1 group had higher serum asprosin than the DN0 group. Serum asprosin was linked to a higher risk of T2DM and DN in a logistic regression analysis. Serum asprosin was found to be positively related with disease duration, systolic blood pressure, blood urea nitrogen, creatinine, uric acid, ACR, calcium channel blockers, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker therapy, but negatively related with glomerular filtration rate, metformin, and acarbose therapy. Conclusion Serum asprosin increase with the progression of DN. Serum asprosin is correlated with renal function and ACR.

Myonectin, a newly discovered myokine, enhances fatty acid uptake in cultured adipocytes and hepatocytes and suppresses circulating levels of free fatty acids in mice. This study is performed to evaluate the association between serum and aqueous humor myonectin concentrations with diabetic retinopathy (DR). This study was performed in a population of 228 patients with type 2 diabetes (T2DM) and 72 control subjects. Diabetic patients were then divided into T2DM patients without DR, non-proliferative diabetic retinopathy (NPDR) patients, and proliferative diabetic retinopathy (PDR) patients. Serum and aqueous humor myonectin concentrations were significantly lower in the case group than in the control group. PDR patients showed significantly decreased serum and aqueous humor myonectin concentrations than in the other two T2DM patients. In addition, NPDR patients showed significantly lower serum and aqueous humor myonectin concentrations than T2DM patients without DR. Logistic regression analysis demonstrated that serum and aqueous humor myonectin was correlated with a decreased risk of T2DM and DR. Simple linear regression analysis showed that serum myonectin was negatively correlated with duration of disease, body mass index (BMI), and HbA1c. Duration of disease and BMI were still correlated with the serum myonectin after a multiple linear regression analysis. Aqueous humor myonectin was negatively correlated with duration of disease, systolic blood pressure (SBP), and diastolic blood pressure. Duration of disease and SBP was still correlated with the aqueous humor myonectin after a multiple linear regression analysis. Our investigation indicates an inverse association of serum and aqueous humor myonectin with DR.

Aim We used a dataset from a cross-sectional survey conducted in China to determine which of the anthropometric indices of obesity are important in terms of carotid atherosclerosis free of cardiovascular and cerebrovascular diseases. Methods A total of 5,245 participants who were volunteering for carotid ultrasound unit in this cross-sectional survey were included in the present analysis. All subjects were free of angina, myocardial infarction, heart failure and stroke, and cancer. A low-risk subgroup was defined as people free of hypertension, diabetes, and hyperlipidemia. All analyses based on logistic regression were gender-specific. Results The present study consisted of 2,501 males and 2,744 females, with 776 (31.03%) diagnosed as carotid artery plaque in males and 550 (20.04%) in females. Univariable analyses in unadjusted logistic model showed significant associations between disease presence and all central obesity indices. After adjusting for more variables, only a body shape index (ABSI) was associated with the presence of disease in both males and females. Moreover, stepwise regression approaches revealed that ABSI was always an independent determinant of the presence of subclinical carotid plaque. Multiple regression shows a linear and significant increase in the prevalence of atherosclerosis in males and females as ABSI decile levels increased. Similar results were obtained when the association between ABSI and carotid plaque was studied in this low-risk subgroup. Conclusions ABSI, as a novel anthropometric indicator compared with traditional indices, was found to have a closer relationship with subclinical carotid atherosclerosis, even in populations free of hypertension, diabetes, and hyperlipidemia.

Background Age-related hearing impairment (ARHI) has attracted increasing attention recently. It is caused by genetic and environmental factors. A number of ARHI-related genes have been found. This study aimed to detect the potential association between NR3C1 gene polymorphisms and ARHI by means of weighted allele score. Methods A total of 861 participants from Qingdao city were selected by means of cluster random sampling. We statistically evaluated the characteristics of individuals and used the Mann–Whitney U test or chi-square test for comparison. The publicly available expression quantitative trait locus (eQTL) was queried on the website of the Genotype-Tissue Expression (GTEx). We used the weighted allele score and logistic regression analysis to explore the association between NR3C1 gene polymorphisms and ARHI. Finally, the prediction model was constructed by logistic regression and receiver operating characteristic (ROC) curve. Results All individuals over 60 years of age were enrolled in this study. The allele of rs61757411, rs41423247 and rs6877893 were significantly different between the ARHI group and the normal hearing group (P NR3C1 gene in artery aorta. Then we performed two models: one without adding any covariates into model and the other adjusting for demographic characteristic, smoking and drinking, diet and exercise, and physical conditions. In the multivariate-adjusted model 2, the odds ratio with 95% confidence interval for weighted allele score (NR3C1) was 0.841 (0.710–0.995, P = 0.043). The area under the ROC curve was 0.755, indicating that the model had good predictability. Conclusions Our study suggests that NR3C1 gene polymorphisms was significantly associated with ARHI.

Objective Adropin, a newly identified regulatory protein encoded by Enho gene, is correlated with insulin sensitivity and diabetes. The aim of this study is to determine whether serum and vitreous adropin concentrations are correlated with the presence of diabetic retinopathy. Methods A population of 165 patients with type 2 diabetes mellitus (52 without diabetic retinopathy, 69 with non-proliferative diabetic retinopathy and 44 patients with proliferative diabetic retinopathy) was enrolled in this study. The control group enrolled 68 healthy subjects who had underwent vitrectomy for retinal detachment. Serum and vitreous adropin concentrations were examined using enzyme-linked immunosorbent assay method. Results Control subjects had significantly higher serum and vitreous adropin concentrations compared with diabetic patients. Serum and vitreous adropin concentrations in proliferative diabetic retinopathy patients were significantly reduced compared with those in non-proliferative diabetic retinopathy patients and type 2 diabetes mellitus patients without diabetic retinopathy. In addition, there were lower serum and vitreous adropin concentrations in non-proliferative diabetic retinopathy patients compared with type 2 diabetes mellitus patients without diabetic retinopathy. Logistic regression analysis revealed that serum and vitreous adropin were associated with a decreased risk of type 2 diabetes mellitus and diabetic retinopathy. Conclusion Serum and vitreous adropin concentrations are negatively associated with the presence of diabetic retinopathy.

Aims This study investigated the association of circulating ceramides in patients with comorbid acute coronary syndrome and type 2 diabetes mellitus (ACS-DM). Methods A total of 761 patients with coronary heart disease who were admitted to the Department of Cardiology at the Chinese PLA General Hospital from March to August 2018 were enrolled in this study. Of these 761 patients, 282 were diagnosed with acute coronary syndrome (ACS). We selected 65 patients with ACS-DM (ACS-DM group; mean age 64.88 years; 38 men) and 65 patients with ACS but without any comorbidities (ACS group; mean age 64.68 years; 38 men); the two groups were matched by age and sex. We determined four circulating ceramides in 130 plasma samples: Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/24:1), and Cer(d18:1/24:0). The ceramides in plasma samples from patients with ACS and those from patients with ACS-DM were compared. Pearson correlation coefficients between individual ceramides and traditional cardiovascular risk factors for the whole study population were calculated. Multiple logistic regression models were used to evaluate the relativity between the ceramide and ACS-DM. Results Compared with the ACS group, the levels of Cer(d18:1/16:0), Cer(d18:1/18:0), and Cer(d18:1/24:1) and their ratios to Cer(d18:1/24:0) were higher in the ACS-DM group and Cer(d18:1/24:0) was lower in the ACS-DM group (P < 0.05). Correlation analysis demonstrated mild-to-moderate correlations of ceramide and traditional cardiovascular risk factors. There were relatively strong correlations of Cer(d18:1/18:0) and Cer(d18:1/24:1) with C-reactive protein, blood lipids, fasting blood glucose, and glycated hemoglobin A1c. In multiple logistic regression models, Cer(d18:1/18:0) [odds ratio (OR) 2.396; 95% confidence interval (CI) 1.103-5.205; P = 0.027], Cer(d18:1/24:1) (OR 2.826; 95% CI 1.158-6.896; P = 0.023), Cer(d18:1/18:0)/Cer(d18:1/24:0) (OR 2.242; 95% CI 1.103-4.555; P = 0.026), and Cer(d18:1/24:1)/Cer(d18:1/24:0) (OR 2.673; 95% CI 1.225-5.836; P = 0.014) were positively correlated with ACS-DM, and Cer(d18:1/24:0) (OR 0.200; 95% CI 0.051-0.778; P = 0.020) was negatively correlated with ACS-DM. Conclusion Circulating ceramides are positively correlated with the risk of ACS-DM comorbidity. These results give a new insight into the pathogenesis of ACS-DM comorbidity and could provide new options for risk estimation.

Meteorin-like (Metrnl), a secreted myokine, is induced in white adipose tissue during cold exposure and in muscle after exercise. The present investigation aims to determine the hypothesis that serum Metrnl concentrations are correlated with diabetic nephropathy (DN).The investigation was performed in a population of 221 patients with type 2 diabetes mellitus (T2DM) and 74 healthy subjects. T2DM patients were divided into three groups: normoalbuminuria (n = 100), microalbuminuria (n = 86), and macroalbuminuria (n = 35) subgroups based on urine albumin to creatinine ratio (ACR).All the three T2DM subgroups showed lower serum Metrnl concentrations compared with the controls. Serum Metrnl concentrations were significantly decreased in T2DM patients with macroalbuminuria group than in the other T2DM subgroups. In addition, T2DM patients with microalbuminuria group had decreased serum Metrnl concentrations compared with those with normoalbuminuria; however, the difference was not significant. Logistic regression analysis demonstrated a correlation between serum Metrnl and a decreased risk of T2DM and DN (OR: 0.954, 95% CI: 0.935-0.973, P 0.001 and OR: 0.981, 95% CI: 0.971-0.997, P = 0.014, respectively). Simply linear regression analysis indicated a negative association between serum Metrnl and duration of disease, body mass index (BMI), HbA1c, blood urea nitrogen, creatinine, uricacid, ACR, and angiotensin-converting enzyme inhibitor/angiotensin II receptor blockers treatment. BMI, HbA1c, and ACR were still correlated with the serum Metrnl after a multiple linear regression analysis.Serum Metrnl concentrations are inversely correlated with renal function and DN.

Preptin is a peptide synthesized and secreted accompanied with insulin from pancreatic β cells. Here, we tested the hypothesis that serum preptin concentrations are correlated with diabetic nephropathy (DN). Our study was performed in a population of 234 patients with type 2 diabetes mellitus (T2DM) and 78 healthy subjects. Patients with T2DM were divided into three groups: normoalbuminuria group (DN0, n=106), microalbuminuria group (DN1, n=90), and macroalbuminuria group (DN2, n=38) according to urine albumin to creatinine ratio (ACR). Serum preptin concentrations were significantly increased in the three T2DM subgroups than those in the controls. DN2 group showed significantly higher serum preptin concentrations compared with DN0 and DN1 groups. Moreover, DN1 group had higher serum preptin concentrations than DN0 group. Serum preptin was correlated with a higher risk of T2DM and DN after logistic regression analysis. Simply linear regression analysis demonstrated a positive correlation between serum preptin and gender, body mass index (BMI), blood urea nitrogen, creatinine, ACR, and a negative correlation between serum preptin and glomerular filtration rate, metformin, acarbose treatment. Gender, BMI, and ACR were still positively correlated with serum preptin after multiple linear regression analysis. Our findings indicate that serum preptin concentrations are associated with renal function and DN.

Supplemental Digital Content is available in the text, β-Ureidopropionase (βUP) deficiency is an autosomal recessive disease caused by abnormal changes in the pyrimidine-degradation pathway. This study aimed to investigate the mutation of β-ureidopropionase gene (UPB1) gene and clinical features of 7 Chinese patients with βUP deficiency. We reported 7 Chinese patients with βUP deficiency who were admitted at Tianjin Children's Hospital. Urine metabolomics was detected by gas chromatography–mass spectrometry (GC–MS). Then genetic testing of UPB1 was conducted by polymerase chain reaction (PCR) method. The patients presented with developmental delay, seizures, autism, abnormal magnetic resonance imaging, and significantly elevated levels of N-carbamyl-β-alanine and N-carbamyl-β-aminoisobutyric acid in urine. Subsequent analysis of UPB1 mutation revealed 2 novel missense mutations (c.851G>T and c.853G>A), 3 previously reported mutations including 2 missense mutations (c.977G>A and c.91G>A) and 1 splice site mutation (c.917-1 G>A). The results suggested that the UPB1 mutation may contribute to βUP deficiency. The c.977G>A is the most common mutation in Chinese population.

Pentraxin 3 (PTX3), a member of a superfamily of conserved proteins, attenuates renal damage in diabetic mice. This study aims to determine whether serum PTX3 concentrations are correlated with the presence of diabetic nephropathy (DN). A total of 160 patients with type 2 diabetes mellitus (T2DM) and 54 healthy subjects were enrolled in this study. Patients with T2DM were divided into three groups in accordance with the levels of urinary albumin excretion (UAE). Serum PTX3 concentrations were determined using an ELISA kit. Serum PTX3 concentrations were significantly higher in patients with T2DM compared with the controls. Patients with T2DM with macroalbuminuria showed higher serum PTX3 concentrations compared with the other three groups. However, there were no significant differences of serum PTX3 concentrations between patients with T2DM with normoalbuminuria and microalbuminuria. Furthermore, a simple regression analysis has shown that serum PTX3 concentrations in patients with T2DM were negatively correlated with body mass index, and positively correlated with blood urea nitrogen, serum creatinine, and UAE. Serum PTX3 concentrations are correlated with DN.

Objective Irisin, a recently identified myokine, is involved in the protection of mice against obesity and diabetes. This study aims to determine the serum and vitreous concentrations of irisin in patients with diabetic nephropathy and diabetic retinopathy. Methods A total of 178 patients with type 2 diabetes mellitus, as well as 22 type 2 diabetes mellitus patients without diabetic retinopathy and 35 patients with proliferative diabetic retinopathy were enrolled in this study. Results Serum irisin concentrations were significantly elevated in the control group compared with those in type 2 diabetes mellitus patients. Furthermore, type 2 diabetes mellitus patients with macroalbuminuria exhibited significantly lower serum irisin concentrations than the controls and type 2 diabetes mellitus patients with normoalbuminuria and microalbuminuria. Simple regression analysis showed that the serum irisin concentrations in type 2 diabetes mellitus patients were negatively correlated with age, fasting plasma glucose, homeostasis model assessment of insulin resistance, blood urea nitrogen, creatinine, and positively correlated with creatinine clearance and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers treatment. Proliferative diabetic retinopathy patients showed significantly decreased serum and vitreous irisin concentrations compared with the control group and type 2 diabetes mellitus patients without diabetic retinopathy. Furthermore, decreased serum and vitreous irisin concentrations were found in type 2 diabetes mellitus patients without diabetic retinopathy than those in the controls. Conclusion Irisin concentrations are associated with the presence of diabetic nephropathy and diabetic retinopathy.

Background Nesfatin-1, originating from its precursor protein called nucleobindin 2 (NUCB2), plays an important role in glucose metabolism and diabetes. The aim of this study is to examine the association of the c.1012C>G (rs757081) polymorphism of NUCB2 gene with the presence of T2DM. Methods This study was performed in a population of 396 patients with T2DM and 196 healthy subjects. The c.1012C>G polymorphism of NUCB2 gene was determined using polymerase chain reaction and sequencing method. Results T2DM patients showed lower CG and GG genotype, as well as G allele frequencies compared with healthy subjects. Logistic regression analysis showed that c.1012C>G polymorphism was associated with a decreased risk of developing T2DM. In addition, GG genotype of NUCB2 was significantly correlated with lower levels of body mass index and fasting plasma glucose in patients with T2DM. Conclusions The c.1012C>G polymorphism of NUCB2 is associated with the decreased risk of developing T2DM in Chinese Han population.

Objective. Adropin is a newly identified regulatory protein encoded by the Enho gene and is critically involved in energy homeostasis and insulin sensitivity. This study aims to determine the correlation of serum adropin concentrations with diabetic nephropathy (DN).Methods. This study consisted of 245 patients with type 2 diabetes mellitus (T2DM) and 81 healthy subjects. Then T2DM patients were divided into normoalbuminuria, microalbuminuria, and macroalbuminuria subgroups based on urine albumin to creatinine ratio (ACR).Results. T2DM patients showed significantly lower serum adropin concentrations than those in the controls. T2DM patients with macroalbuminuria had significantly decreased serum adropin concentrations compared with the other three groups. In addition, T2DM patients with microalbuminuria showed lower serum adropin concentrations than those in patients with normoalbuminuria. Logistic regression analysis showed that serum adropin was correlated with decreased risk of developing T2DM and DN. Pearson correlation analysis indicated that serum adropin was negatively correlated with body mass index (BMI), blood urea nitrogen, creatinine, and ACR and positively correlated with glomerular filtration rate. Furthermore, multiple linear regression analysis showed that BMI and ACR were negatively correlated with serum adropin levels.Conclusion. Serum adropin concentrations are negatively associated with renal function. Adropin may be implicated in the pathogenesis of DN development.

Objective: Pentraxin 3 (PTX3), an acute-phase glycoprotein, is correlated with inflammation. Inflammation is mechanistically involved in the development of diabetic retinopathy (DR). This study was performed to investigate the association of serum and vitreous PTX3 concentrations with the occurrence of DR. Methods: This study enrolled 52 type 2 diabetes mellitus (T2DM) patients (20 without DR and 32 patients with proliferative diabetic retinopathy [PDR]). Serum and vitreous PTX3 concentrations were examined by using an enzyme-linked immunosorbent assay. Results: PDR patients showed significantly increased concentrations of serum and vitreous PTX3 concentrations compared with the control group and T2DM patients without DR. Higher serum and vitreous PTX3 concentrations were detected in T2DM patients without DR than those in the controls. Conclusion: Serum and vitreous PTX3 concentrations are associated with the occurrence of DR.

It is well established that smooth muscle contractility is regulated by an elevation of cytosolic Ca2+ via myosin light chain phosphorylation, which is activated by myosin light chain kinase (MLCK). Recently, MLCK has been demonstrated to play an important role in smooth muscle contraction and normal gastrointestinal motility. The aim of our study is to investigate whether MLCK is involved in the mechanism of gastrointestinal dysfunction and the ameliorating effects of insulin on gastrointestinal dysfunction in diabetic rats. A diabetic rat model was established by an intravenous injection with streptozotocin. Rats were randomized into three groups: control group, diabetic group, and insulin-treated group. The gastrointestinal functions were assessed in terms of gastric emptying and intestinal transit. The expression of MLCK in the pylorus and ileum of the three groups was determined by real-time polymerase chain reaction (PCR) and Western blot methods. The diabetic group exhibited a significant delay in gastric emptying and intestinal transit than the control group. Insulin treatment significantly ameliorated the gastric emptying and intestinal transit in diabetic rats. The expression levels of MLCK in the pylorus and ileum of the diabetic group were both significantly decreased compared with the control group, and the changes of MLCK expression in these tissues of diabetic rats were partially reversed after treatment with insulin. Decreased expression of MLCK in gastrointestinal tissues could be a possible cause for gastrointestinal dysfunction. Insulin may partly ameliorate gastrointestinal dysfunction by restoring the expression of MLCK.

Insulin replacement therapy is essential in type 1 diabetic individuals and is required in ~40- 50% of type 2 diabetics during their lifetime. Prior attempts at beta cell regeneration have relied upon pancreatic injury to induce beta cell proliferation, dedifferentiation and activation of the embryonic pathway, or stem cell replacement. We report an alternative method to transform adult non-stem (somatic) cells into pancreatic beta cells. The Cellular Networking, Integration and Processing (CNIP) approach targets cellular mechanisms involved in pancreatic function in the organ's adult state and utilizes a synergistic mechanism that integrates three important levels of cellular regulation to induce beta cell formation: (i) glucose metabolism, (ii) membrane receptor function, and (iii) gene transcription. The aim of the present study was to induce pancreatic beta cell formation in vivo in adult animals without stem cells and without dedifferentiating cells to recapitulate the embryonic pathway as previously published (1-3). Our results employing CNIP demonstrate that: (i) insulin secreting cells can be generated in adult pancreatic tissue in vivo and circumvent the problem of generating endocrine (glucagon and somatostatin) cells that exert deleterious effects on glucose homeostasis, and (ii) longterm normalization of glucose tolerance and insulin secretion can be achieved in a wild type diabetic mouse model. The CNIP cocktail has the potential to be used as a preventative or therapeutic treatment or cure for both type 1 and type 2 diabetes.

Chemerin is shown to be associated with inflammation which is involved in the pathogenesis of diabetic nephropathy. This study aims to determine whether rosiglitazone and pioglitazone ameliorate renal function through an effect on the expression of chemerin and ChemR23 in streptozotocin-induced diabetic rats. The rats were randomized to control, diabetic, rosiglitazone-, and pioglitazone-treated groups. The expression level of chemerin and ChemR23 in the renal tissues was significantly elevated in the diabetic group compared with the control group. Rosiglitazone inhibited the overexpression of chemerin and ChemR23, while pioglitazone inhibited the overexpression of ChemR23 in the kidney of diabetic rats. In addition, chemerin expression level was positively correlated with transforming growth factor-β1, connective tissue growth factor, tumor necrosis factor-α, and intracellular cell adhesion molecule-1 expression in diabetic rats. Rosiglitazone ameliorates diabetic nephropathy by reducing the expression of chemerin and ChemR23 in diabetic rats.

Objective Previous studies demonstrated that G1359A polymorphism of cannabinoid receptor-1 (CNR1) was associated with cardiovascular risk factors including obesity, insulin resistance, dyslipidemia, and inflammation, which are also risk factors for developing type 2 diabetes mellitus (T2DM). Therefore, this study was aimed to determine whether G1359A polymorphism of CNR1 is associated with T2DM and the presence of coronary artery disease (CAD) in patients with T2DM. Methods A total of 450 patients with T2DM (259 patients with CAD and 191 patients without CAD) and 94 healthy subjects were genotyped using polymerase chain reaction and restriction fragment length polymorphism method. Results No significant differences in genotype frequency of CNR1 were found between normal controls and patients with T2DM without CAD. GG genotype frequency of CNR1 was significantly higher in the patients with T2DM with CAD compared with those without CAD and healthy subjects ( P = 0.003 and P = 0.005, respectively). Unconditional logistic regression analysis revealed that GG genotype was significantly associated with the presence of CAD in the patients with T2DM compared with GA and AA genotypes (odds ratio, 2.632; 95% confidence interval, 1.481–4.678; P < 0.001). In addition, GG genotype of CNR1 was significantly correlated with elevated levels of body mass index, systolic blood pressure, homeostasis model assessment of insulin resistance, and C-reactive protein, as well as decreased levels of high-density lipoprotein cholesterol in patients with T2DM. Conclusions G1359A polymorphism of CNR1 may be not associated with T2DM but may contribute to the genetic risk for the presence of CAD in patients with T2DM of Chinese Han population.