Missense mutation of ISL1 (E283D) is associated with the development of type 2 diabetes.

AIMS/HYPOTHESIS: Mutations in Isl1, encoding the insulin enhancer-binding protein islet-1 (ISL1), may contribute to attenuated insulin secretion in type 2 diabetes mellitus. We made an Isl1E283D mouse model to investigate the disease-causing mechanism of diabetes mellitus. METHODS: The ISL1E283D mutation (c. 849A>T) was identified by whole exome sequencing on an early-onset type 2 diabetes family and then the Isl1E283D knockin (KI) mouse model was created and an IPGTT and IPITT were conducted. Glucose-stimulated insulin secretion (GSIS), expression of Ins2 and other ISL1 target genes and interacting proteins were evaluated in isolated pancreas islets. Transcriptional activity of Isl1E283D was evaluated by cell-based luciferase reporter assay and electrophoretic mobility shift assay, and the expression levels of Ins2 driven by Isl1 wild-type (Isl1WT) and Isl1E283D mutation in rat INS-1 cells were determined by RT-PCR and western blotting. RESULTS: Impaired GSIS and elevated glucose level were observed in Isl1E283D KI mice while expression of Ins2 and other ISL1 target genes Mafa, Pdx1, Slc2a2 and the interacting protein NeuroD1 were downregulated in isolated islets. Transcriptional activity of the Isl1E283D mutation for Ins2 was reduced by 59.3%, and resulted in a marked downregulation of Ins2 expression when it was overexpressed in INS-1 cells, while overexpression of Isl1WT led to an upregulation of Ins2 expression. CONCLUSIONS/INTERPRETATION: Isl1E283D mutation reduces insulin expression and secretion by regulating insulin and other target genes, as well as its interacting proteins such as NeuroD1, leading to the development of glucose intolerance in the KI mice, which recapitulated the human diabetic phenotype. This study identified and highlighted the Isl1E283D mutation as a novel causative factor for type 2 diabetes, and suggested that targeting transcription factor ISL1 could offer an innovative avenue for the precise treatment of human type 2 diabetes.

A greater ratio of thigh subcutaneous fat to abdominal fat is associated with protection against non-alcoholic fatty liver disease.

Background & Aims: No prospective studies have examined the association between thigh subcutaneous fat distribution and non-alcoholic fatty liver disease (NAFLD). We investigated the associations of thigh subcutaneous fat distribution with incidence and remission of NAFLD in a community-based prospective cohort. Methods: We followed 1,787 subjects, who underwent abdominal ultrasonography, abdominal and femoral magnetic resonance imaging scans, and anthropometric assessments. Associations of thigh subcutaneous fat area/abdominal fat area ratio and thigh circumference/waist circumference ratio with incidence and remission of NAFLD were estimated using the modified Poisson regression model. Results: Over a mean 3.6-year follow-up, 239 incident cases of NAFLD and 207 regressed cases of NAFLD were identified. Increasing thigh subcutaneous fat area/abdominal fat area ratio was associated with a lower risk of incident NAFLD and a higher likelihood of remission of NAFLD [risk ratio (RR) per SD: 0.69, 95% CI 0.59-0.81; 1.20, 95% CI 1.07-1.34, respectively). Each one SD increase in thigh circumference/waist circumference ratio was associated with a 16% lower risk of incident NAFLD (RR 0.84, 95% CI 0.76-0.94) and a 22% higher likelihood of remission of NAFLD (RR 1.22, 95% CI 1.11-1.34). Additionally, the effects of thigh subcutaneous fat area/abdominal fat area ratio on the incidence and remission of NAFLD were mediated through adiponectin (14.9% and 26.6%), homeostasis model assessment of insulin resistance (9.5% and 23.9%), and triglyceride (7.5% and 19.1%). Conclusions: These results demonstrated that a favourable fat distribution, characterised by a greater ratio of thigh subcutaneous fat to abdominal fat, had a protective role against NAFLD. Impact and implications: The associations of thigh subcutaneous fat distribution with NAFLD incidence and remission have not been prospectively examined in a community-based cohort. Our findings suggest that greater thigh subcutaneous fat relative to a given amount of abdominal fat has a protective effect against NAFLD among the middle-aged and older Chinese populations.

ClusterSeg: A crowd cluster pinpointed nucleus segmentation framework with cross-modality datasets.

The detection and segmentation of individual cells or nuclei is often involved in image analysis across a variety of biology and biomedical applications as an indispensable prerequisite. However, the ubiquitous presence of crowd clusters with morphological variations often hinders successful instance segmentation. In this paper, nuclei cluster focused annotation strategies and frameworks are proposed to overcome this challenging practical problem. Specifically, we design a nucleus segmentation framework, namely ClusterSeg, to tackle nuclei clusters, which consists of a convolutional-transformer hybrid encoder and a 2.5-path decoder for precise predictions of nuclei instance mask, contours, and clustered-edges. Additionally, an annotation-efficient clustered-edge pointed strategy pinpoints the salient and error-prone boundaries, where a partially-supervised PS-ClusterSeg is presented using ClusterSeg as the segmentation backbone. The framework is evaluated with four privately curated image sets and two public sets with characteristic severely clustered nuclei across a variety range of image modalities, e.g., microscope, cytopathology, and histopathology images. The proposed ClusterSeg and PS-ClusterSeg are modality-independent and generalizable, and superior to current state-of-the-art approaches in multiple metrics empirically. Our collected data, the elaborate annotations to both public and private set, as well the source code, are released publicly at https://github.com/lu-yizhou/ClusterSeg.

Effect of changes in anthropometric measurements on the remission and progression of prediabetes: A community-based cohort study.

AIMS: We assessed the impact of changes in body mass index (BMI), body fat percentage (BF%), and waist circumference (WC) on prediabetes among middle-aged and elderly Chinese adults. SUBJECTS, MATERIALS AND METHODS: 2.5-year changes in BMI, BF%, and WC were calculated by subtracting baseline levels from follow-up, based on a cohort of 3,632 participants with prediabetes, and outcomes were defined as remission to normal glucose regulation (NGR), persistence in prediabetes, and progression to newly diagnosed diabetes mellitus (NDM). RESULTS: Among participants with prediabetes, 16.9% returned to NGR and 24.6% progressed to NDM. Changes in BMI, BF%, but not WC were associated with remission and progression of prediabetes (risk ratio per standard deviation increase of BMI: 0.86 [0.79-0.93] and 1.15 [1.08-1.23]; BF%: 0.91 [0.84-0.98] and 1.11 [1.03-1.19]). Among participants with combined impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), only BF% change was significantly associated with remission of prediabetes. CONCLUSION: Short-term management of BMI and BF% should be emphasized to promote the remission and prevent the progression of prediabetes. Moreover, it is of particular clinical importance to monitor BF% among people with combined IFG and IGT.

Identification and management of GCK-MODY complicating pregnancy in Chinese patients with gestational diabetes.

Precise differentiation of glucokinase (GCK) monogenic diabetes from gestational diabetes mellitus (GDM) is critical for accurate management of the pregnancy outcome. We screened GCK-MODY complicating pregnancies in Chinese GDM patients, explored the pathogenesis of novel GCK mutations, and evaluated the patients' pregnancy outcome and management. The GCK gene from 411 GDM patients was screened with PCR-direct sequencing and multiplex ligation-dependent probe amplification (MLPA) and 15 GCK mutations were identified. We also retrospectively analyzed a total of 65 pregnancies from 21 GCK-MODY families, wherein 41 were from 15 maternal families and 24 were from six paternal families. Bioinformatic analysis and biochemical functional study were conducted to identify novel GCK mutations. In total, we identified 21 GCK mutations: 15 from the 411 GDM patients and six from 24 fathers. Of th Asp78Asn (GAC → AAC), Met87Arg (ATG → AGG), Leu451Val (CTT → GTT), Leu451Pro (CTG → CCG) and 1019 + 20G > A e mutations, five, i.e., were novel and deleterious, with markedly decreased enzyme activity and thermal stability. The unaffected offspring of GCK mutation-affected mothers were heavier than affected offspring (p < 0.001). Of 21 insulin-treated affected mothers, 10 had maternal hypoglycemia (47.6%) and seven had perinatal complications (33.3%), and the affected offspring of the insulin-treated affected mothers had significantly lower birth weights than that of the 20 diet-control affected mothers (p = 0.031). In this study, the prevalence of GCK-MODY complicating pregnancy in Chinese GDM patients was 3.6% (15/411). The defective GCK may contribute to the hyperglycemia in GCK-MODY. Insulin therapy is not beneficial for GCK-MODY complicating pregnancy and therefore should not be recommended.

Osteocalcin and Risks of Incident Diabetes and Diabetic Kidney Disease: A 4.6-Year Prospective Cohort Study.

OBJECTIVE: We aimed to examine the relationship between osteocalcin (OC) and the risk of incident diabetes and the risk of incident diabetic kidney disease (DKD). RESEARCH DESIGN AND METHODS: We followed 5,396 participants without diabetes (nondiabetes subcohort) and 1,174 participants with diabetes and normal kidney function (diabetes subcohort) at baseline. Logistic regression and modified Poisson regression models were used to estimate the relative risk (RR) of baseline OC levels with incident diabetes and DKD. RESULTS: During a mean 4.6-year follow-up period, 296 cases of incident diabetes and 184 cases of incident DKD were identified. In the nondiabetes subcohort, higher OC levels were linearly associated with a decreased risk of diabetes (RR for 1-unit increase of loge-transformed OC 0.51 [95% CI 0.35-0.76]; RR for highest vs. lowest quartile 0.65 [95% CI 0.44-0.95]; P for trend < 0.05). In the diabetes subcohort, OC levels were linearly inversely associated with incident DKD (RR for 1-unit increase of loge-transformed OC 0.49 [95% CI 0.33-0.74]; RR for highest vs. lowest quartile 0.56 [95% CI 0.38-0.83]; P for trend < 0.05), even independent of baseline estimated glomerular filtration rate and urinary albumin-to-creatinine ratio. No significant interactions between OC and various subgroups on incident diabetes or DKD were observed. CONCLUSIONS: Lower OC levels were associated with an increased risk of incident diabetes and DKD.

Novel ceruloplasmin gene mutation causing aceruloplasminemia with diabetes in a Chinese woman: a case report.

Hereditary aceruloplasminemia (ACP) is a rare adult-onset autosomal recessive disease characterized by a ceruloplasmin (CP) gene mutation and defective or absent CP function. In the present study, we report a case of ACP in a 34-year-old Chinese woman with diabetes, fatigue, anxiety, and progressive membrane loss with low hemoglobin associated with microcytosis. The fasting glucose level was 5.6-7.96 mmol/L. Postprandial blood glucose ranged from 6.8 to 9.6 mmol/L. The Stumvoll first-phase and second-phase insulin secretion disposition indices were very low, and the serum iron content was low, even though transferrin levels were normal. Moreover, the transferrin saturation was low (5%), and the ferritin level was extremely high, above 2,000 µg/L in the patient. Furthermore, her serum CP level was extremely low (<0.0183 g/L). Abdominal computed tomography (CT) examination showed moderate iron overload in the liver. Brain CT also showed a mildly increased density of the bilateral thalami and basal ganglia. Finally, gene analysis showed a rare homozygous mutation (c.146+1G>A) in the CP gene and was diagnosed with ACP. To date, less than 60 family cases of ACP have been reported worldwide, and only two cases of ACP have been reported in China. Here, we report a case of ACP accompanied by diabetes with a novel mutation of the CP gene, which suggests that increased awareness should be highlighted in this disorder as diabetes is an important typical symptom.

Function of a Psychological Nursing Intervention on Depression, Anxiety, and Quality of Life in Older Adult Patients With Osteoporotic Fracture.

BACKGROUND: Osteoporotic fracture is a serious complication of osteoporosis. The long-term therapy process and the heavy restriction to physical activities give rise to a psychological burden on osteoporotic fracture patients, especially older adult patients. Psychological nursing interventions significantly alleviate negative emotional reactions in cancer patients. This research aimed to investigate the function of psychological nursing interventions in the reduction of depression and anxiety and the improvement of quality of life in older adult patients with osteoporotic fracture. METHODS: Osteoporotic fracture patients (n = 106) were divided into control group (n = 53) or intervention group (n = 53). In the control group, the participants were given conventional nursing care. In the intervention group, the participants were given psychological nursing interventions. Anxiety, depression, and quality of life were evaluated and compared between the two groups. RESULTS: After 5 weeks of psychological nursing intervention, the anxiety and depression scores significantly decreased in the intervention group. The Mental Function in Quality of Life Questionnaire of the European Foundation for Osteoporosis score also decreased in the intervention group. LINKING EVIDENCE TO ACTION: Psychological nursing interventions alleviate anxiety and depression in older adult osteoporotic fracture patients and enhance their mental function.

Serum Glycated Albumin Levels Are Affected by Alcohol in Men of the Jinuo Ethnic Group in China.

AIM: To investigate the effects of alcohol on serum glycated albumin (GA) levels in Chinese men. METHODS: A total of 2314 male subjects from the Jinuo ethnic group in China were enrolled. Of these, 986 subjects drank alcohol frequently and 404 subjects did not. Lifestyle information was gathered by using a questionnaire, and measurements of blood pressure, body mass index, blood glucose level, liver function, and kidney function were collected. GA was measured by using an enzymatic method. Frequent drinking was defined as a history of drinking ethanol > 80 g/d within the past two weeks. Nondrinking was defined as no alcohol consumption in the past three months. Subjects with an alcohol intake between 0 and 80 g/d in the past two weeks were included in the drinking-occasionally group. Analysis of variance (ANOVA), correlation analysis, and linear regression were used to evaluate the effects of drinking on serum GA levels. Decision tree regression (DTR) algorithm was used to evaluate the effect of features (variables) on GA levels. RESULTS: We found that male subjects who drank frequently had significantly lower serum GA levels than subjects who did not drink (13.0 ± 1.7 vs. 14.1 ± 3.7, p < 0.05). Spearman's correlation analysis calculated a coefficient of -0.152 between drinking and GA (p < 0.005). Linear regression established that drinking was an independent predictor for GA levels with a standardized regression coefficient of -0.144 (p < 0.05). Decision tree regression showed that the effect of drinking on GA levels (0.0283) is five times higher than that of smoking (0.0057). CONCLUSIONS: Frequent alcohol consumption could result in decreased GA levels in men of the Jinuo ethnic group in China.

Quantitative analysis of abnormalities in gynecologic cytopathology with deep learning.

Cervical cancer is one of the most frequent cancers in women worldwide, yet the early detection and treatment of lesions via regular cervical screening have led to a drastic reduction in the mortality rate. However, the routine examination of screening as a regular health checkup of women is characterized as time-consuming and labor-intensive, while there is lack of characteristic phenotypic profile and quantitative analysis. In this research, over the analysis of a privately collected and manually annotated dataset of 130 cytological whole-slide images, the authors proposed a deep-learning diagnostic system to localize, grade, and quantify squamous cell abnormalities. The system can distinguish abnormalities at the morphology level, namely atypical squamous cells of undetermined significance, low-grade squamous intraepithelial lesion, high-grade squamous intraepithelial lesion, and squamous cell carcinoma, as well as differential phenotypes of normal cells. The case study covered 51 positive and 79 negative digital gynecologic cytology slides collected from 2016 to 2018. Our automatic diagnostic system demonstrated its sensitivity of 100% at slide-level abnormality prediction, with the confirmation with three pathologists who performed slide-level diagnosis and training sample annotations. In the cellular-level classification, we yielded an accuracy of 94.5% in the binary classification between normality and abnormality, and the AUC was above 85% for each subtype of epithelial abnormality. Although the final confirmation from pathologists is often a must, empirically, computer-aided methods are capable of the effective extraction, interpretation, and quantification of morphological features, while also making it more objective and reproducible.

Gene Expression Profiling of Type 2 Diabetes Mellitus by Bioinformatics Analysis.

OBJECTIVE: The aim of this study was to identify the candidate genes in type 2 diabetes mellitus (T2DM) and explore their potential mechanisms. METHODS: The gene expression profile GSE26168 was downloaded from the Gene Expression Omnibus (GEO) database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs). Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Metascape for annotation, visualization, and comprehensive discovery. The protein-protein interaction (PPI) network of DEGs was constructed by using Cytoscape software to find the candidate genes and key pathways. RESULTS: A total of 981 DEGs were found in T2DM, including 301 upregulated genes and 680 downregulated genes. GO analyses from Metascape revealed that DEGs were significantly enriched in cell differentiation, cell adhesion, intracellular signal transduction, and regulation of protein kinase activity. KEGG pathway analysis revealed that DEGs were mainly enriched in the cAMP signaling pathway, Rap1 signaling pathway, regulation of lipolysis in adipocytes, PI3K-Akt signaling pathway, MAPK signaling pathway, and so on. On the basis of the PPI network of the DEGs, the following 6 candidate genes were identified: PIK3R1, RAC1, GNG3, GNAI1, CDC42, and ITGB1. CONCLUSION: Our data provide a comprehensive bioinformatics analysis of genes, functions, and pathways, which may be related to the pathogenesis of T2DM.

Development and validation of screening scores of non-alcoholic fatty liver disease in middle-aged and elderly Chinese.

AIM: Non-alcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease and also closely related to cardiometabolic disease. Its prevalence was estimated at over one-fourth in the general population in China. We aimed to develop effective score tools for detecting NAFLD. METHODS: A total of 17,212 participants aged 45-70 years old were surveyed in Shanghai between 2013 and 2014, and 13,293 participants were included in this analysis. All participants were randomly classified into the exploratory group or the validation group. Candidate categorical variables were selected using a logistic regression model. The score points were generated according to the ß-coefficients. RESULTS: We developed the Shanghai Nicheng NAFLD Score I (SHNC NAFLD Score I), which included body mass index and waist circumference with an area under the receiver-operating characteristic curve (AUC) of 0.802 (95% CI 0.792-0.811) in the exploratory group and 0.802 (95% CI 0.793-0.812) in the validation group. We further developed the SHNC NAFLD Score II by adding fasting plasma glucose, triglyceride, and alanine aminotransferase/aspartate aminotransferase ratio to the SHNC NAFLD Score I, achieving an AUC of 0.852 (95% CI 0.843-0.861) in the exploratory group and 0.843 (95% CI 0.834-0.852) in the validation group. The two score tools also performed well in subjects with normal alanine aminotransferase (ALT) levels. CONCLUSIONS: Based on anthropometric and clinical categorical variables, our two scores are effective tools for detecting NAFLD in both this southern Chinese population and their subpopulation with normal ALT levels.

miR-26a Attenuated Bone-Specific Insulin Resistance and Bone Quality in Diabetic Mice.

Diabetes mellitus is a prevalent disease result in several complications, including bone problems. Previous studies have shown that microRNA (miR)-26a regulates glucose metabolism and plays a protective role in diabetes. However, whether miR-26a also affects bone quality in diabetes remains unknown. In the present study, we evaluated the potential effects of miR-26a on bone in diabetic mice. We administrated miR-26a in streptozotocin-induced diabetic mice. The metabolic parameters, bone quality, osteoblast and osteoclast markers, and insulin signaling activation were measured. miR-26a ameliorated insulin resistance and glucose tolerance, improved bone microarchitecture and quality, increased osteoblasts and bone formation, decreased osteoclasts, and promoted the insulin signaling pathway in diabetic mice. These effects were abolished in insulin receptor-compromised Col1a1-Insr+/- mice. In conclusion, miR-26a could ameliorate bone-specific insulin resistance and bone quality in diabetic mice, which depended on the insulin receptors on osteoblasts. Our findings highlight the potential of miR-26a as a therapeutic target for diabetes mellitus-related bone metabolism and diseases.

Transplantation of IL-10-Overexpressing Bone Marrow-Derived Mesenchymal Stem Cells Ameliorates Diabetic-Induced Impaired Fracture Healing in Mice.

BACKGROUND: Diabetes mellitus is characterized by hyperglycemia which displays insufficiency or resistance to insulin. One of the complications of diabetes is the increased risk of fracture and the impairment of bone repair and regulation. There have been evidences from previous studies that mesenchymal stem cells (MSCs) from bone marrow promote cartilage and callous formation. In addition, IL-10, an anti-inflammatory cytokine, has been observed to relieve inflammation-related complications in diabetes. METHODS: In this study, the role of IL-10-overexpressing bone marrow-derived MSCs (BM-MSCs) was examined in the diabetic mice model with femur fracture. MSCs were isolated from the BALB/c mice and IL-10 over expression was conducted with lentivirus transduction. The streptozotocin (STZ)-induced diabetes model with femoral fracture was established. BM-MSCs with IL-10 over expression were transplanted into the fracture area. The expressions of inflammatory factors IL-6, TNF-α and INF-γ were examined by qPCR and immunoblot; the biomechanical strength of the fracture site of the mice was examined and evaluated. RESULTS: Data showed that IL-10 overexpressed BM-MSCs transplantation decreased inflammatory response, promoted bone formation, and increased the strength of the fracture site in STZ-induced diabetic mice with femoral fracture. CONCLUSION: IL-10 overexpressed BM-MSCs transplantation accelerated fracture repair in STZ-induced diabetic mice, which in turn provides potential clinical application prospects.

The promotion of bone regeneration through CS/GP-CTH/antagomir-133a/b sustained release system.

Few studies reported the application of miRNA in bone regeneration. In this study, the expression of miR133a and miR133b in murine BMSCs was inhibited via antagomiR-133a/b and the osteogenic differentiation in murine BMSCs was evaluated. The RT-PCR, flow cytometry, cell counting kit-8, and annexin V-FITC/PI double staining assays were performed. Double knockdown miR133a and miR133b can promote BMSC osteogenic differentiation. At optimum N/P ration (15:1), the loading efficiency can reach over 90%. CTH-antagomiR-133a/b showed no cytotoxicity to BMSCs and diminished miR133a and miR133b expression in BMSCs. Furthermore, chitosan-based sustained delivery system can facilitate continuous dosing of antagomiR-133a/b, which enhanced calcium deposition and osteogenic specific gene expression in vitro. The new bone formation was enhanced after the sustained delivery system containing CTH-antagomiR-133a/b nanoparticles was used in mouse calvarial bone defect model. Our results demonstrate that CTH nanoparticles could facilitate continuous dosing of antagomiR133a/b, which can promote osteogenic differentiation.

ATP6V1H facilitates osteogenic differentiation in MC3T3-E1 cells via Akt/GSK3ß signaling pathway.

Type 2 diabetes mellitus (T2DM) accounts for approximately 90% of all diabetic patients, and osteoporosis is one of the complications during T2DM process. ATP6V1H (V-type proton ATPase subunit H) displays crucial roles in inhibiting bone loss, but its role in osteogenic differentiation remains unknown. Therefore in this study, we aimed to explore the biological role of ATP6V1H in osteogenic differentiation. OM (osteogenic medium) and HG (high glucose and free fatty acids) were used to induce the MC3T3-E1 cells into osteogenic differentiation in a T2DM simulating environment. CCK8 assay was used to detect cell viability. Alizarin Red staining was used to detect the influence of ATP6V1H on osteogenic differentiation. ATP6V1H expression increased in OM-MC3T3-E1 cells, while decreased in OM+HG-MC3T3-E1 cells. ATP6V1H promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. Overexpression of ATP6V1H inhibited Akt/GSK3ß signaling pathway, while knockdown of ATP6V1H promoted Akt/GSK3ß signaling pathway. ATP6V1H overexpression promoted osteogenic differentiation of OM+HG-MC3T3-E1 cells. The role of ATP6V1H in osteogenic differentiation in a T2DM simulating environment involved in Akt/GSK3ß signaling pathway. These data demonstrated that ATP6V1H could serve as a potential target for osteogenic differentiation in a T2DM simulating environment.

Development and validation of a non-invasive assessment tool for screening prevalent undiagnosed diabetes in middle-aged and elderly Chinese.

To develop a non-invasive assessment tool and compare it to other assessment tools among middle-aged and elderly Shanghainese, 15,309 individuals, who were 45-70 years old, not previously diagnosed with diabetes, and from a cross-sectional survey conducted between April 2013 and August 2014 in Shanghai, were selected into this study. The participants were randomly assigned to either the exploratory group or the validation group. Undiagnosed diabetes was defined according to the American Diabetes Association diagnostic criteria, and score points were generated according to the logistic regression coefficients. Age, family history of diabetes, hypertension, overweight/obesity, and central obesity all contributed to the constructed model, the Shanghai Nicheng diabetes screening score, with the area under the receiver-operating characteristic curve (AUC) being 0.654 (95% CI 0.637-0.670) in the exploratory group and 0.669 (95% CI 0.653-0.686) in the validation group. The score value of 6 was the optimal cut-point with the largest Youden's index. When applied to the validation group, our model had a similar discriminative ability to the New Chinese Diabetes Risk Score (AUC: 0.669 vs. 0.662, p = 0.187), and performed better than other screening scores for Chinese. However, our model was inferior to fasting plasma glucose, 2-hour plasma glucose, and glycosylated hemoglobin in detecting prevalent undiagnosed diabetes (AUC: 0.669 (0.653-0.686) vs. 0.881 (0.868-0.894), 0.934 (0.923-0.944), and 0.834 (0.819-0.848), all p < 0.001). Although non-invasive models, based on demographic and clinical information, are advisable in resource-scarce developing areas, regular blood glucose screening is still necessary among those aged 45 or older.

Association between serum somatostatin levels and glucose-lipid metabolism in the Jino ethnic minority and Han Chinese population.

We aim to investigate the relationship between serum somatostatin (SST) levels and glucose-lipid metabolism at various stages of glucose tolerance in the Jino ethnic minority (n=111) and Han population (n=113) of Yunnan Province, southwest China. Anthropometric parameters and biochemical traits were measured. Serum SST and plasma glucagon levels were tested. Participants were divided into three subgroups: isolated fasting hyperglycemia (IFH), isolated post challenge hyperglycemia (IPH) and normal glucose tolerance (NGT). SST levels were found lower while glucagon levels were significantly higher in the Jino ethnic with IPH (P=0.0026 and P=0.0069, respectively). Fasting glucose and high density lipoprotein-cholesterol (HDL-C) levels were higher (P=0.0055 and P=0.0021, respectively) and fasting insulin levels and homeostasis model assessments ß-cell function were lower (P=0.0479 and P=0.0007, respectively) in the Jino population. After adjusting for confounding factors, the serum SST level was associated with glucagon (P<0.0001) in both populations. The SST level was correlated with fasting Cpeptide (P=0.0267) in Jino and HDL-C levels in Han (P=0.0079). Our findings suggest that serum SST levels and plasma glucagon levels may vary in subjects with IPH between two ethnics.

Serum adropin levels are decreased in Chinese type 2 diabetic patients and negatively correlated with body mass index.

Adropin has been identified as potent regulatory hormone implicated in insulin sensitivity and the maintenance of energy homeostasis. The aim of current study was to investigate serum adropin concentrations of type 2 diabetes mellitus (T2DM) patients in the fasting status, especially those overweight/obese and evaluate the relationships between adropin levels and metabolic parameters. A total of 116 T2DM patients and 60 controls with normal glucose tolerance (NGT) were recruited to the study. Adropin concentration was determined using commercial ELISA kits. Anthropometric characteristics were collected and biochemistry, glycosylated hemoglobin A1c (HbA1c) and fasting insulin (FIns) were detected by clinical laboratory. Insulin resistance was estimated by homeostasis model 2 assessment of insulin resistance (HOMA2-IR). Serum adropin levels in Chinese T2DM patients were decreased compared with the controls [3.8 (3.0-5.5) vs. 5.5 (3.7-7.9) ng/mL, p < 0.01]. Meanwhile, overweight/obese patients had more considerably reduced levels of adropin. Adropin level was negatively correlated with body mass index (BMI), high-sensitive C reactive protein (hs-CRP), triglycerides (TG), fasting plasma glucose (FPG), FIns, HOMA2-IR and HbA1c, while positively with high-density lipoprotein cholesterol (HDL-C) in study participants (p < 0.01). The correlations of adropin with glucolipid variables (TG, HDL-C, FPG, FIns, HOMA2-IR, HbA1c) still existed after adjusting the effect of BMI. Besides, HOMA2-IR and HbA1c were independent factors associated with serum adropin levels. Binary logistic regression analyses showed that adropin was significantly associated with T2DM after removing confounding factors (p < 0.01). Receiver operating characteristic (ROC) curve demonstrated adropin concentration of 5.8 ng/mL could be used as a possible optimal cut-off value to identify T2DM from non-T2DM with sensitivity of 81.9% and specificity of 46.7%. Serum adropin concentrations are decreased in Chinese T2DM patients, especially those overweight/obese. Adropin, associated with glucolipid homeostasis and insulin sensitivity, may implicate in the pathogenesis of T2DM.

Mutation screening for thalassaemia in the Jino ethnic minority population of Yunnan Province, Southwest China.

OBJECTIVES: This study aimed to detect α- and ß-thalassaemia mutations in the Jino ethnic minority population of Yunnan Province, Southwest China. DESIGN: A total of 1613 Jino adults were continuously recruited from February 2012 to April 2012. Fasting venous blood samples were obtained to determine haematological variables. Haemoglobin analysis was conducted using high-performance liquid chromatography. Participants with hypochromic microcytic anaemia or positive haemoglobin analysis profiles were confirmed by α- and ß-globin genetic testing, including DNA microarray analysis, direct sequencing methods and multiplex gap-PCR assays. SETTING: Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Jiao Tong University Affiliated Sixth People's Hospital. RESULTS: We found 363 suspected cases by primary screening of haematological variables and haemoglobin analysis. After further genetic testing, four types of α- and ß-thalassaemia mutation were detected in 203 out of 363 individuals. Both α(0)- and α(+)-thalassaemia mutations, --(SEA) and -α(3.7), were identified. ß-Thalassaemia mutations included CD17 (HBB:c.52A>T) and CD26 (HbE or HBB:c.79G>A). In addition, 13 HbE carriers had coexisting α(0)- or α(+)-thalassaemia deletions. Clinical haematological variables indicated that, in this study, carriers of all thalassaemic genotypes had more severe hypochromic microcytic anaemia than non-thalassaemic individuals. CONCLUSIONS: Our results provide information on the Jino ethnic minority that may be useful for further genetic counselling, prenatal screening and clinical diagnosis of thalassaemia in this region.