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.

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.

Identification and validation of NOLC1 as a potential target for enhancing sensitivity in multidrug resistant non-small cell lung cancer cells.

Adjuvant chemotherapy has become the frequently adopted standard therapeutic approach for non-small cell lung cancer (NSCLC). However, the development of multidrug resistance (MDR) is a major obstacle contributing to the failure of chemotherapy. This study aimed to identify genes associated with MDR development that predict tumor response to chemotherapy in NSCLC. In the present study, a multidrug-resistant NSCLC cell sub-line, A549/MDR, was established from the A549/DDP cell line and characterized. The resistance index (RI) of this subline was calculated according to the IC50 of A549/MDR relative to the parental A549/DDP cells. The gene expression profiles of A549/DDP and A549/MDR were obtained using an oligonucleotide microarray (Agilent SureHyb microarray chip). The microarray results were validated by qRT-PCR and selected genes were analyzed by in vitro loss-of-function experiments. Gene expression profiling identified 921 differentially expressed genes (DEGs) according to the selection criteria, in which 541 genes were upregulated and 380 genes were downregulated in A549/MDR compared with A549/DDP cells. We found that these DEGs are involved in diverse biological processes, including ribonucleoprotein complex, drug metabolism, the Hippo signaling pathway and transcriptional misregulation. NOLC1, as one of the identified DEGs, was confirmed to be overexpressed in A549/MDR cells and its knockdown significantly enhanced the drug sensitivity of A549/MDR cells in response to multidrug treatment. Furthermore, knockdown of NOLC1 downregulated the expression levels of drug resistance-associated molecules (LRP and MDR1) in A549/MDR cells. These findings provide a new and comprehensive expression profile of MDR in NSCLC cells. Identification and validation of NOLC1 might be a promising therapeutic strategy for the management of MDR of NSCLC patients.