Periostin Acts as a Bridge between Gestational Diabetes Mellitus (GDM) and Chronic Inflammation to Modulate Insulin Resistance by Modulating PPARα/NF-κB/TNF-α Signaling Pathway.

INTRODUCTION: Gestational diabetes mellitus (GDM) is considered an imbalance of glucose metabolism and insulin resistance during pregnancy. AIMS/OBJECTIVE: To evaluate the levels of periostin (POSTN) in patients with GDM and investigate the association between POSTN and GDM. MATERIALS AND METHODS: A total of 30 pregnant women (NC group) and 30 pregnant women with GDM (GDM group) were involved. The GDM mouse model was established by intraperitoneally injecting streptozotocin. The oral glucose tolerance test (OGTT), insulin, and insulin resistance indices were tested. An immunohistochemical and Western blot assay was conducted to determine the expression of POSTN, PPARα, TNF-α, and NF-κB. HE staining was performed to evaluate inflammation in the placental tissues of women with GDM and GDM mice. POSTN-siRNA was transfected into glucose-pretreated HTR8 cells, and pAdEasy-m-POSTN shRNA was infected in GDM mice. The RT-PCR assay determined the gene transcription of POSTN, TNF-α, NF-κB, and PPARα. RESULTS: Pregnantwomen in theGDMgroup demonstrated significantly higherOGTT (p < 0.05), insulin levels (p < 0.05) and insulin resistance (p < 0.05) compared to those of the NC group. The serum levels of POSTN in pregnantwomen of theGDMgroup were significantly higher than that of theNC group (p < 0.05). The obvious inflammation was activated in pregnant women in the GDMgroup. POSTN-siRNAsignificantly enhanced the cell viability of glucose-treated HTR8 cells compared to that without glucose treatment (p < 0.05). POSTNsiRNA (pAdEasy-m-POSTN shRNA) markedly reduced the glucose level of glucose-treated HTR8 cells (GDM mice) compared to that without treatment (p < 0.05). POSTN-siRNA (pAdEasy-m-POSTN shRNA) promoted PPARα gene transcription (p < 0.05) and inhibited NF-κB/TNF-α gene transcription (p < 0.05) in glucose-treated HTR8 cells (GDMmice) compared to thosewithout treatment. POSTN-siRNAmodulated NF- κB/TNF-α pathway mediated inflammation by regulating PPARα in HTR8 cells and GDMmice. PPARα participated in POSTN-associated inflammation. pAdEasy-m-POSTN shRNA inhibited T-CHO/TG levels in GDM mice compared to those without treatment (p < 0.05). All the effects of POSTN-siRNA (pAdEasy-m- POSTN shRNA) were obviously blocked by PPARα inhibitor treatment. CONCLUSION: POSTN levels were significantly higher in pregnant women with GDM and were associated with chronic inflammation and PPARα expression. POSTN may act as a bridge between GDM and chronic inflammation to modulate insulin resistance by modulating PPARα/NF-κB/TNF-α signaling pathway.

Low serum albumin levels and high neutrophil counts are predictive of a poorer prognosis in patients with metastatic breast cancer.

Breast cancer is a severe disease with high incidence and mortality rates in menopausal women. Previous studies have shown that nutritional status and inflammation play a significant role in the development of breast cancer. However, whether serum albumin (ALB) and neutrophils (NE) accelerate the progression of this disease remains unclear. In the present study, a total of 94 cases of newly diagnosed metastatic breast cancer were assessed. For analysis, 26 risk factors including ALB and NE were assessed. Multivariate Cox proportional hazards regression analysis was then used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) after adjusting for continuous and categorical covariates. Compared with the control group, patients with disease progression, low levels of ALB, higher NE, counts, and higher neutrophil to lymphocyte ratio counts were associated with worse overall survival (OS). When these risk factors were fitted into a multivariate regression model, progression [P<0.001, HR=3.03 (1.62-5.66)], NE counts ≥3.370×109 [P=0.004, HR=2.15 (1.27-3.65)] and ALB levels <43.275 g/l [P=0.008, HR=0.47 (0.27-0.82)] remained statistically significant factors for a worse OS. These independently associated risk factors were used to form an OS estimation nomogram. The constructed nomogram demonstrated good accuracy in estimating risk, with a bootstrap-corrected C index of 0.686. We further collected data on 30 patients for external validation and found the nomogram had an accuracy of 83.3%. In conclusion, low serum ALB levels and increased NE counts were predictive of a poorer prognosis in patients with metastatic breast cancer. Nomograms based on the multivariate analysis showed a good predictive ability for estimating the risk of OS.

Decreased complement 4d increases poor prognosis in patients with non-small cell lung cancer combined with gastrointestinal lymph node metastasis.

Lung cancer is a common malignancy that is difficult to treat and has a high risk of mortality. Although gastrointestinal lymph node metastasis has long been known to exert major impact on the prognosis of lung cancer, the mechanism of its occurrence and potential biological markers remain elusive. Therefore, the present study retrospectively analyzed data from 132 patients with non-small cell lung cancer (NSCLC) combined with lymph node metastasis between February 2010 and April 2019 from the First Affiliated Hospital of Soochow University (Suzhou, China) and Sichuan Cancer Hospital (Chengdu, China). Overall survival was assessed using Kaplan-Meier analysis and Cox logistic regression model. In addition, a prediction model was constructed based on immune indicators such as complement C3b and C4d (measured by ELISA), before the accuracy of this model was validated using calibration curves for 5-year OS. Among the 132 included patients, a total of 92 (70.0%) succumbed to the disease within 5 years. Multifactorial analysis revealed that complement C3b deficiency increased the risk of mortality by nearly two-fold [hazard ratio (HR)=2.23; 95% CI=1.20-4.14; P=0.017], whilst complement C4d deficiency similarly increased the risk of mortality by two-fold (HR=2.14; 95% CI=1.14-4.00; P=0.012). The variables were subsequently screened using Cox model to construct a prediction model based on complement C3b and C4d levels before a Nomogram plotted. By internal validation for the 132 patients, the Nomogram accurately estimated the risk of mortality, with a corrected C-index of 0.810. External validation of the model in another 50 patients from Sichuan Cancer Hospital revealed an accuracy of 77.0%. Overall, this mortality risk prediction model constructed based on complement levels showed accuracy in assessing the prognosis of patients with metastatic NSCLC. Therefore, complement C3b and C4d have potential for use as biomarkers to predict the risk of mortality in such patients.

Genome-wide association study of fasting proinsulin, fasting insulin, 2-hour postprandial proinsulin, and 2-hour postprandial insulin in Chinese Han people.

INTRODUCTION: Fasting proinsulin (FPI) and fasting insulin (FI) have been demonstrated to be associated with impaired b cell function, T2DM, and insulin resistance. This genome-wide association study (GWAS) was performed to contribute to our understanding of the genetic basis of FPI, FI, 2-hour postprandial proinsulin (2hPI), and 2-hour postprandial insulin (2hI) of the pathophysiology of prediabetes in the Chinese population. MATERIAL AND METHODS: The levels of fasting plasma glucose (FPG), FPI, FI, 2hPI, and 2hI were examined by an automatic biochemical analyser. The Applied BiosystemsTM AxiomTM Precision Medicine Diversity Array, the Gene Titan Multi-Channel instrument, and Axiom Analysis Suite 6.0 Software were used for genotyping. Imputation was performed with IMPUTE 2.0 software from HapMap, 1000 Genomes Phase 3 as a reference panel. RESULTS: Six single nucleotide polymorphisms (SNPs) in DLG1-AS1, SORCS1, and CTAGE11P for FPI, and 27 SNPs in ZNF718, MARCHF2, and HNRNPM for 2hPI reached genome-wide significance. Genome-wide significance was reached for associations of 6 SNPs in KRT71 to FI. Also, 14 SNPs in UBE2U, ABO, and GRID1-AS1 were genome-wide significant in their relationship with 2hI. Among these, the genetic loci of CTAGE11P, MARCHF2, KRT71, and ABO have the strongest association with FPI, 2hPI, FI, and 2hI. CONCLUSIONS: The genetic variants of CTAGE11P, MARCHF2, KRT71, and ABO are significantly correlated with FPI, 2hPI, FI, and 2hI, respectively, in Chinese Han people. These genetic variants may serve as new biomarkers for the prevention of prediabetes.

An Investigation on the Risk Factors of Thyroid Diseases in Community Population in Hainan.

Background: In recent years, the incidence of thyroid diseases has increased significantly, which has seriously affected people's work and life. The purpose of this study was to explore the epidemiological characteristics of thyroid diseases and autoantibodies. Method: According to the principle of overall sampling, resident residents ≥18 years and who will not move within 5 years are randomly selected. A total of 2136 eligible individuals were divided into case and control groups according to whether they have thyroid disease. Finally, the impact of potential risk factors on thyroid diseases was evaluated. Results: The overall prevalence of thyroid disease was 58.3%, and there was a significant difference in the prevalence of thyroid disease between women and men (p = 0.004). Except for the age group ≥70 years, with the increase in age, the prevalence gradually increased (p < 0.05). Participants with positive thyroid autoantibodies (TPOAb or TgAb) had a higher prevalence than participants with negative autoantibodies. The positive rate of autoantibodies in women was higher than that in men (p < 0.05). UIC (p = 0.004) and free thyroid hormone (FT4) (p = 0.001) levels of men were higher than those of women, and the TSH level of women was higher than that of men (p = 0.002). The regression analysis showed that women, older age, and family history of thyroid disease were independent risk factors for thyroid disease. Conclusion: The prevalence of thyroid diseases in Hainan was high. Women are more susceptible to thyroid disease than men, and the prevalence increased with age.

Elevated air quality index and fine particulate matter levels contribute to the poor prognosis and progression of nonsmall-cell lung cancer: A cohort study combined with external validation.

BACKGROUND: Poor air quality can result in a variety of respiratory disorders. However, the air quality index (AQI) and the level of fine particulate matter (PM2.5) on the progression and prognosis of nonsmall-cell lung cancer (NSCLC) are unclear. METHODS: We launched a cohort study focused on the relationship between air quality and overall survival as well as progression, incorporating data from 590 patients with NSCLC in our medical center between November 1, 2013 and March 1, 2016. Forty-nine patients from Sichuan Cancer Hospital were used for validation. RESULTS: Cases with poorer AQI 6 months before NSCLC diagnosis were more likely to progress to stage III to IV NSCLC than controls (OR = 2.61, 95% CI 1.35-5.24, p = 0.005). Similarly, if exposed to high levels of PM2.5 during these 6 months, overall survival was poor (HR [95% CI] = 1.53 [1.13, 2.07], p = 0.006). According to multivariate analysis, age, gender, KPS, PM2.5, hyperlipemia, and NSCLC stage were independent risk factors of overall survival. A predictive model developed by these factors above yielded a favorable agreement (C-index = 0.758) on the calibration curve. External validation was conducted by 46 patients from Sichuan Cancer Hospital displaying an AUC of 0.724 (0.684-0.763). CONCLUSIONS: PM2.5 and AQI levels affect disease progression and long-term survival in NSCLC patients. An overall survival prediction model based on the PM2.5 level can help clinicians predict the risk of death in NSCLC.

Genetic Variants Relate to Fasting Plasma Glucose, 2-Hour Postprandial Glucose, Glycosylated Hemoglobin, and BMI in Prediabetes.

Diabetes mellitus (DM) is a chronic disease that seriously threatens human health. Prediabetes is a stage in the progression of DM. The level of clinical indicators including fasting plasma glucose (FPG), 2-h postprandial glucose (2hPG), and glycosylated hemoglobin (HbA1C) are the diagnostic markers of diabetes. In this genome-wide association study (GWAS), we aimed to investigate the association of genetic variants with these phenotypes in Hainan prediabetes. In this study, we recruited 451 prediabetes patients from the residents aged ≥18 years who participated in the National Diabetes Prevalence Survey of the Chinese Medical Association in 2017. The GWAS of FPG, 2hPG, HbA1C, and body mass index (BMI) in prediabetes was analyzed with a linear model using an additive genetic model with adjustment for age and sex. We identified that rs13052524 in MRPS6 and rs62212118 in SLC5A3 were associated with 2hPG in Hainan prediabetes (p = 4.35 × 10-6, p = 4.05 × 10-6, respectively). Another six variants in the four genes (LINC01648, MATN1, CRAT37, and SLCO3A1) were related to HbA1C. Moreover, rs11142842, rs1891298, rs1891299, and rs11142843 in TRPM3/TMEM2 and rs78432036 in MLYCD/OSGIN1 were correlated to BMI (all p < 5 × 10-6). This study is the first to determine the genome-wide association of FPG, 2hPG, and HbA1C, which emphasizes the importance of in-depth understanding of the phenotypes of high-value susceptibility gene markers in the diagnosis of prediabetes.

Low level of complement factor H increases the risk of cancer-related death in patients with small-cell lung cancer.

INTRODUCTION: Pulmonary cancer is a kind of deeply invasive tumour which is difficult to treat, and its mortality rate is high. Previous research has shown that activation of complement could contribute to the progression of non-small-cell lung cancer (SCLC). However, little research has been done on SCLC. METHODS: Complement factor H (CFH), complements C3 as well as C4 were measured in patients, and the prognostic impact of different parameters was assessed by log-rank function analysis and Cox multifactor models. Besides, we constructed a predictive model based on complement fractions and validated the accuracy of the model. RESULTS: Among these 242 patients, 200 (82.6%) died. The median survival time was 18.3 months. We found by multifactorial analysis that high levels of CFH decreased the risk of death (HR 0.23, 95% CI 0.10 to 0.57, p<0.001), while elevated complement C4 displayed poor prognosis (HR 2.28, 95% CI 1.66 to 3.13, p<0.001). We screened variables by Cox models and constructed CFH-based prediction models to plot a nomogram by internal validation. The nomogram showed excellent accuracy in assessing the probability of death, yielding an adjusted C-statistics of 0.905. CONCLUSIONS: CFH can be recognised as a biomarker to predict the risk of death in SCLC. The prediction model established based on CFH, C3 and C4 levels has good accuracy in patients' prognostic assessment.

Increased diastolic blood pressure and apnea time contribute to the poor apnea and hypopnea index and life quality of primary snoring: a cohort study combined with external validation.

Obstructive sleep apnea hypoventilation syndrome (OSAHS) is a common sleep breathing disorder closely associated with cardiovascular disease. However, the respiratory sleep and related cardiovascular parameters on the apnea and hypopnea index (AHI) and life quality of primary snoring are unclear. We launched a cohort study focused on the association between respiratory sleep and cardiovascular-related parameters and apnea and hypopnea index, incorporating data from 218 patients with primary snoring in our medical center between Jun 1, 2015, and Apr 1, 2016. Thirty patients from Sichuan Cancer Hospital were used for validation. Patients with longer apnea time were more likely to progress to higher AHI (> 30) than controls (OR = 5.66, 95% CI = [2.79, 11.97], p < 0.001). Similarly, if patients have a higher value of diastolic blood pressure, they will also have a higher AHI (> 30) (HR [95% CI] = 3.42 [1.14, 13.65], p = 0.043). According to multivariate analysis, longest apnea time, the mean percentage of SaO2, and neckline length were independent risk factors of overall survival. A predictive model developed based on these factors above yielded a favorable agreement (C-index = 0.872) on the calibration curve. Thirty patients conducted external validation from Sichuan Cancer Hospital, displaying an AUC of 0.833 (0.782-0.884). Increased diastolic blood pressure and apnea time affect AHI level. An AHI prediction model based on these factors above can help clinicians predict the risk of high AHI events.

RSPH14 regulates the proliferation, cell cycle progression, and apoptosis of non-small cell lung cancer cells.

Non-small cell lung cancer (NSCLC) is the most common subtype of lung cancer, and it is characterized by a high incidence. It is important to understand the molecular mechanisms that determine the progression and metastasis of NSCLC in order to develop more effective therapies and identify novel diagnostic indicators of NSCLC. RSPH14 has been reported to be related to multiple human diseases, including duodenal adenocarcinoma and meningiomas, but the role of RSPH14 in NSCLC remains unclear. The present study aimed to investigate the molecular function and clinical significance of RSPH14 in NSCLC. Analyses of public datasets and clinical samples demonstrated that RSPH14 expression was upregulated in NSCLC samples compared with normal samples. In addition, high RSPH14 expression was associated with a shorter overall survival time in patients with NSCLC. Notably, RSPH14 knockdown suppressed the proliferation and cell cycle progression and enhanced the apoptosis of NSCLC cells. Mechanically, tandem mass tag analysis demonstrated that RSPH14 can affect multiple processes, including the AMPK signaling pathway, calcium ion import regulation, glucose transmembrane transporter activity, and glucose transmembrane transport. Taken together, the results of the present study suggest that RSPH14 may be a promising prognostic factor and therapeutic target for NSCLC.

The Impact of Different Insulin-Related Measures on the Risk of Prediabetes Among the Chinese Han Population.

INTRODUCTION: Diabetes mellitus (DM) has a serious impact on people's lives in the world. Interventions that affect risk factors for prediabetes can prevent and reduce diabetes occurrence. Proinsulin (PI), true insulin (TI), and proinsulin to insulin ratio (PI/TI) are risk factors for diabetes. The roles of these indicators in prediabetes are unclear. This study aimed to evaluate the impact of PI, TI, PI/TI, 2-h proinsulin (2hPI), 2-h true insulin (2hTI), and 2hPI/2hTI on the risk of prediabetes among the Chinese Han population. METHODS: This cross-sectional study recruited 1688 subjects including 718 prediabetes cases and 970 non-prediabetes controls from Hainan Affiliated Hospital of Hainan Medical University. The cases involved 292 men and 426 women. The controls involved 324 men and 646 women. The mean age was 53.62 ± 12.43 years in the prediabetes group and 44.24 ± 12.87 years in the non-prediabetes group. RESULTS: Our results showed that PI, TI, PI/TI, 2hPI, 2hTI, and 2hPI/2hTI were significantly correlated with prediabetes (all p < 0.05). Logistic regression analysis revealed that PI (OR 1.022, 95% CI 1.014-1.031, p = 0.00011), TI (OR 1.005, 95% CI 1.003-1.007, p = 0.00012), PI/TI (OR 1.517, 95% CI 1.080-2.131, p = 0.016), and 2hTI (OR 1.000, 95% CI 1.000-1.001, p = 0.002) were significantly associated with an increased risk of prediabetes. Receiver operating characteristic curve (ROC) analysis indicated that the area under the ROC curve (AUC) of the combination (PI + TI + PI/TI + 2hPI + 2hTI + 2hPI/2hTI) in diagnosing prediabetes was 0.627, which was larger than the diagnostic value of HOMA-IR (AUC 0.614) and HOMA-ß (AUC 0.387). CONCLUSIONS: Our study showed that PI, TI, PI/TI, and 2hTI could significantly enhance the risk of prediabetes in the Chinese Han population, which suggested that PI, TI, PI/TI, and 2hTI might be available risk factors for prediabetes.

Low prevalence of vitamin D deficiency in adult residents in Hainan, the tropical island province of China.

BACKGROUND: Vitamin D deficiency is considered to be a global health problem. The purpose of this study was to evaluate the prevalence of vitamin D deficiency and analyze its related factors among adult residents in Hainan, a tropical island province of southern China. METHODS: A total of 1,700 healthy adults, aged 18-86 years (617 men and 1,073 women), were enrolled in our cross-sectional descriptive study. Binomial logistic regression analyses were performed to identify possible predictors of vitamin D status. RESULTS: The average serum 25-hydroxyvitamin D [25(OH)D] concentration was 37.66±10.77 ng/mL (males 43.60±11.8 ng/mL, females 34.20±8.40 ng/mL; I<0.001). The proportions of vitamin D sufficiency [25(OH)D ≥30 ng/mL], insufficiency [20 ng/mL ≤25(OH)D <30 ng/mL], and deficiency [25(OH)D <20 ng/mL] were 76.6%, 20.5%, and 2.9%, respectively. Vitamin D deficiency in the young, middle-aged, and elderly groups were 4.2%, 2.7%, and 1.7%, respectively. Vitamin D sufficiency was found to be positively associated with male sex (P<0.0001), age >40 years (P=0.014), habitation in a rural area (P<0.0001), summer/autumn seasons (P<0.0001), and having <13 years of formal education (P<0.0001). CONCLUSIONS: Our study was the first to assess the vitamin D status and analyze related factors among adult residents in Hainan Province, China. We found that vitamin D deficiency has low prevalence in this population, suggesting that before developing a strategy for the clinical use of vitamin D supplements in a region, the levels of vitamin D in generally healthy populations of that region should be assessed, to avoid unnecessary supplementation.

emEminepygia/em emmyanmarensis/em sp. nov., a new Earwig (Dermaptera) Nymph in Burmese Amber.

A new fossil earwig nymph, Eminepygia myanmarensis gen. et sp. nov. (Pygidicranidae), from the mid-Cretaceous amber of Myanmar, is described and figured. Eminepygia myanmarensis gen. et sp. nov. can be readily distinguished from all other extinct and recent members of Dermaptera by the prominent bulges on the last three terga. Our new finding sheds further light on the diversity and morphological disparity of fossil dermapterans during the Late Mesozoic.

Type 2 diabetes is more predictable in women than men by multiple anthropometric and biochemical measures.

Men and women are sexually dimorphic but whether common anthropometric and biochemical parameters predict type 2 diabetes (T2D) in different ways has not been well studied. Here we recruit 1579 participants in Hainan Province, China, and group them by sex. We compared the prediction power of common parameters of T2D in two sexes by association, regression, and Receiver Operating Characteristic (ROC) analysis. HbA1c is associated with FPG stronger in women than in men and the regression coefficient is higher, consistent with higher prediction power for T2D. Age, waist circumference, BMI, systolic and diastolic blood pressure, triglyceride levels, total cholesterol, LDL, HDL, fasting insulin, and proinsulin levels all predict T2D better in women. Except for diastolic blood pressure, all parameters associate or tend to associate with FPG stronger in women than in men. Except for diastolic blood pressure and fasting proinsulin, all parameters associate or tend to associate with HbA1c stronger in women than in men. Except for fasting proinsulin and HDL, the regression coefficients of all parameters with FPG and HbA1c were higher in women than in men. Together, by the above anthropometric and biochemical measures, T2D is more readily predicted in women than men, suggesting the importance of sex-based subgroup analysis in T2D research.

A new species and genus of Alienopteridae (Blattodea) from mid-Cretaceous amber of northern Myanmar.

Eminespina burma gen. et sp. nov., is described and illustrated based on a female embedded in Cretaceous Burmese amber of Cenomanian age. Autapomorphic are three unique spines distributed anterior quarter of pronotum from longer posterior part. The new evidence of Batesian mimicry in the insect fossil record is briefly discussed.

A new fossil record of Lymexylidae (Insecta: Coleoptera) from mid-Cretaceous amber of northern Myanmar.

The fossil ship-timber beetle, Adamas hukawngensis gen. et sp.n., is described and defined based on one well preserved specimen in mid-Cretaceous amber from the Hukawng Valley in Northern Myanmar. The new species can be readily distinguished from all other extinct and recent members of the family due to the presence of a lozenge-shaped scutellum with a meso-longitudinal groove. Modifications of lymexylid metathoracic wing venation and palaeobiomigratory significance are briefly discussed.

The correlation between proinsulin, true insulin, proinsulin: True insulin ratio, 25(OH) D3, waist circumference and risk of prediabetes in Hainan Han adults.

PURPOSE: Diabetes mellitus is a kind of highly prevalent chronic disease in the world. The intervention measures on the risk factors of prediabetes contribute to control and reduce the occurrence of diabetes. This study aimed to investigate the correlation between proinsulin (PI), true insulin (TI), PI/TI, 25(OH) D3, waist circumference (WC), and risk of prediabetes. METHODS: In this cross-sectional study, 1662 subjects including 615 prediabetes and 1047 non-prediabetes were recruited. Spearman's correlation analysis was used to explore the association of PI, TI, PI/TI, 25(OH) D3, and waist circumference with prediabetes. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. Receiver-Operator Characteristic (ROC) curve was used to evaluate the risk of prediabetes. RESULTS: Our study showed that FPI, 2hPI, FTI, 2hTI, FPI/FTI, and WC could enhance the risk of prediabetes (OR 1.034; OR 1.007; OR 1.005; OR 1.002; OR 3.577, OR 1.053, respectively; all p< 0.001). Stratified analyses indicated that FPI/FTI associated with an increased risk of prediabetes in men (OR 2.080, p = 0.042). FTI have a weak association with prediabetes risk in men and women (OR 0.987, p = 0.001; OR 0.994, p = 0.004, respectively). 2hPI could decrease prediabetes in women (OR 0.995, p = 0.037). Interesting, the sensitivity (86.0%) and AUC (0.942, p< 0.001) of combination (FPI+FTI+2hPI+2hTI+25(OH) D3+WC) were higher than the diagnostic value of these alone diagnoses. The optimal cutoff point of FPI, FTI, 2hPI, 2hTI, 25(OH) D3, and WC for indicating prediabetes were 15.5 mU/l, 66.5 mU/l, 71.5 mU/l, 460.5 mU/l, 35.5 ng/ml, and 80.5 cm, respectively. What's more, the combination (FPI+FTI+2hPI+2hTI+25(OH) D3+WC) significantly improved the diagnostic value beyond the alone diagnoses of prediabetes in men and women (AUC 0.771; AUC 0.760, respectively). CONCLUSION: The FPI, 2hPI, FTI, 2hTI, FPI/FTI, and WC significantly associated with an increased risk of prediabetes. The combination of FPI, FTI, 2hPI, 2hTI, 25(OH) D3, and WC might be used as diagnostic indicators for prediabetes.

Silencing cyclophilin A improves insulin secretion, reduces cell apoptosis, and alleviates inflammation as well as oxidant stress in high glucose-induced pancreatic ß-cells via MAPK/NF-kb signaling pathway.

Cyclophilin A is increased in the plasm of diabetic patients, while its effects on high glucose (HG)-stimulated pancreatic ß-cells are still pending. The aim of this research is to investigate the effects of cyclophilin A inhibition on HG-challenged pancreatic ß-cells. For investigating the effects of cyclophilin A decrease on HG-induced pancreatic ß-cells, the cells were separated into normal glucose (NG), Mannitol, HG, HG + shRNA-NC, and HG + shRNA-Cyclophilin A-1 groups. The protein and mRNA expression were detected via Western blot and qRT-PCR. CCK-8 assay and flow cytometry were employed for assessing cell viability and apoptosis. The levels of oxidative stress, inflammation, and insulin secretion were detected by corresponding kits. The cyclophilin A was higher in HG group. Knockdown of cyclophilin A was able to increase insulin secretion, decrease cell apoptosis, and alleviate inflammation as well as oxidant stress in HG-treated pancreatic ß-cells via MAPK/NF-kb pathway. Taken together, Cyclophilin A, highly expressed in pancreatic ß-cells induced by HG, is a promising therapeutic target for diabetes. Knockdown of cyclophilin A has protective effects against HG-challenged pancreatic ß-cells via regulation of MAPK/NF-kb pathway. The findings in this study provided a new strategy for diabetic treatment and paved the way for future researches on diabetes treatment.

Subgroup analysis of proinsulin and insulin levels reveals novel correlations to metabolic indicators of type 2 diabetes.

Proinsulin, insulin and proinsulin/insulin (P/I) ratio have been reported to be correlated with fasting plasma glucose (FPG) and Hemoglobin A1c (HbA1c) in whole population study therefore sensitive predictors of T2D progression. However, by analyzing data collected from 2018-2019 from a cohort of 1579 East Asian individuals from Hainan Province of China, we find that the associations of proinsulin, insulin and P/I ratio with diabetic indicators have distinct, sometimes opposite regression patterns in normal, prediabetic and diabetic subgroups. The strength of the associations are generally weak in normal and prediabetic groups, and only moderate in diabetic group between postprandial proinsulin and HbA1c, between postprandial insulin and FPG or HbA1c, and between postprandial P/I ratio and FPG or HbA1c. Receiver operating characteristic (ROC) curve analysis shows these parameters are weaker than age in predicting diabetes development, with P/I ratio being the weakest. Proinsulin and insulin levels are tightly associated with insulin sensitivity across all subgroups, as measured by Matsuda index. Together, our results suggest that proinsulin, insulin or P/I ratio are weak predictors of diabetes development in the whole population, urging the need for stratifying strategies and novel perspectives in evaluating and predicting hyperglycemia progression.