Exosome-derived tRNA fragments tRF-GluCTC-0005 promotes pancreatic cancer liver metastasis by activating hepatic stellate cells.

Early metastasis is the primary factor in the very poor prognosis of pancreatic ductal adenocarcinoma (PDAC), with liver metastasis being the most common form of distant metastasis in PDAC. To investigate the mechanism of PDAC liver metastasis, we found that PDAC cells can promote the formation of pre-metastatic niches (PMNs) through exosomes to facilitate liver metastasis in the early stage. In our study, hepatic stellate cells (HSCs) were treated with PDAC-derived exosomes (PDAC-exo), and the activation of HSCs was detected. A novel transfer RNA-derived fragment, the tRF-GluCTC-0005 was obtained by small RNA sequencing from serum exosomes of PDAC patients. Bioinformatics analysis and RNA pull-down assays revealed the interaction between WDR1 and tRF-GluCTC-0005. A KPC transgenic mouse model and an AAV-mediated sh-WDR1 mouse model were used to detect the mechanism of liver metastasis in vivo. Finally, the dual luciferase reporter assay, protein mutation truncation assay, Co-IP assay, and flow cytometry assay were used to explore the molecular mechanism in HSCs activation and PMNs formation. We found that the tRF-GluCTC-0005 in exosomes binds to the 3' untranslated region of the mRNA of the WDRl in HSCs and increases mRNA stability. The N-terminals of WDR1 bind to the YAP protein directly, inhibit YAP phosphorylation, and promote the expression of YAP transcription factors. The tRF-GluCTC-0005 in PDAC-exo significantly recruits myeloid-derived suppressor cells (MDSCs) in the liver, creating a PMNs immunosuppressive microenvironment and further advancing liver metastasis from PDAC. Our results suggest that the key of PDAC liver metastasis is the activation of HSCs through upregulation of WDR1 by tRF-GluCTC-0005 in exosomes, which mediates the infiltration of MDSCs to form PMNs.

Liquid-liquid phase separation-related lncRNA prognostic signature and ZNF32-AS2 as a novel biomarker in hepatocellular carcinoma.

BACKGROUND: Liquid-liquid phase separation (LLPS) enhances oncogenic signaling pathways and advances cancer progression, and has been proposed as a promising cancer biomarker and intervention target. Nevertheless, doubts remain about the prognostic importance of LLPS-related long non-coding RNAs (lncRNAs) in hepatocellular carcinoma (HCC). METHODS: An LLPS-related lncRNA prognostic signature was generated by drivers and regulators of LLPS, and was validated in external datasets. The underlying genetic changes and functional enrichment of the signature were assessed. The drug sensitivity and response to immunotherapy were predicted in patients categorized as high-risk and low-risk. Clinical samples, phase separation agonist, and dispersant were used to identify lncRNAs with the most significant expression change. Cancer cells with ZNF32-AS2 expression regulation were subjected to colony formation assay, scratch test assay, migration and invasion assay, sorafenib resistance assay, and xenograft tumor model. RESULTS: The signature of LLPS-related hub lncRNAs identified through Weighted Gene Co-Expression Network Analysis showed outstanding performance in training and external validation cohorts consistently, and the molecular characteristics varied between different risk groups. Potential drugs for high-risk individuals were identified, and low-risk individuals demonstrated a more favorable reaction to immunotherapy. ZNF32-AS2 showed the most significant expression change in phase separation agonist and dispersant treatment. ZNF32-AS2 promoted the proliferation, mobility, and sorafenib resistance of liver cancer cells. CONCLUSIONS: The LLPS-related lncRNA signature may help assess prognosis and predict treatment efficacy in clinical settings. LLPS-related ZNF32-AS2 promoted the proliferation, mobility, and sorafenib resistance of liver cancer cells, and may be a novel potential biomarker in hepatocellular carcinoma.

Efficacy and Safety of Eplerenone for Treating Chronic Kidney Disease: A Meta-Analysis.

Background: In recent years, a large amount of clinical evidence and animal experiments have demonstrated the unique advantages of mineralocorticoid receptor antagonists (MRA) for treating chronic kidney disease (CKD). Aims: Accordingly, the present study aimed to systematically assess the second-generation selective MRAs eplerenone's safety and effectiveness for treating CKD. Methods: Four databases (PubMed, The Cochrane Library, Embase, and Web of Science) were searched for randomized controlled trials (RCT) correlated with eplerenone for treating CKD up to September 21, 2022. By complying with the inclusion and exclusion criteria, literature screening, and data extraction were conducted. Results: A total of 19 randomized controlled articles involving 4501 cases were covered. As suggested from the meta-analysis, significant differences were reported with the 24-h urine protein (MD = -42.23, 95% confidence interval [CI] = -76.72 to -7.73, P = 0.02), urinary albumin-creatinine ratio (UACR) (MD = -23.57, 95% CI = -29.28 to -17.86, P < 0.00001), the systolic blood pressure (SBP) (MD = -2.73, 95% CI = -4.86 to -0.59, P = 0.01), and eGFR (MD = -1.56, 95% CI = -2.78 to -0.34, P = 0.01) in the subgroup of eplerenone vs placebo. The subgroups of eplerenone vs placebo (MD = 0.13, 95% CI = 0.07 to 0.18, P < 0.00001) and eplerenone vs thiazide diuretic (MD = 0.18, 95% CI = 0.13 to 0.23, P < 0.00001) showed the significantly increased potassium levels. However, no statistical significance was reported between the eplerenone treatment groups and the control in the effect exerted by serum creatinine (MD=0.03, 95% CI = -0.01 to 0.07, P = 0.12) and diastolic blood pressure (DBP) (MD = 0.11, 95% CI = -0.41 to 0.63, P = 0.68). Furthermore, significant risks of hyperkalemia were reported in the eplerenone group (K+ ≥ 5.5 mmol/l, RR = 1.70, 95%CI = 1.35 to 2.13, P=<0.00001; K+≥6.0 mmol/l, RR = 1.61, 95% CIs = 1.06 to 2.44, P = 0.02), respectively. Conclusions: Eplerenone has beneficial effects on CKD by reducing urinary protein and the systolic blood pressure, but it also elevates the risk of hyperkalemia.

Branched-chain and aromatic amino acid levels response to an oral glucose load associated with gestational diabetes mellitus.

Serum branched chain amino acids (BCAAs) and aromatic amino acids (AAAs) are associated with obesity, insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the levels of these amino acids in women with gestational diabetes mellitus (GDM) and examined their changes in response to an oral glucose tolerance test (OGTT). 110 women were enrolled and underwent a 75-g OGTT during their second trimester; 43 women were diagnosed with GDM and 67 women did not have GDM (non-GDM women). During the OGTT, fasting, 1-h, and 2-h blood samples were obtained. BCAA and AAA levels were measured by liquid chromatography-tandem mass spectrometry. The differences in BCAA and AAA levels between GDM and non-GDM women were not evident during fasting but became significant after glucose loading. Glucose ingestion decreased the levels of BCAAs and AAAs in both groups. Notably, GDM women showed a delayed and blunted decrease in these amino acids compared to non-GDM women. The risks of 2-h changes in BCAAs and AAAs for GDM women were significant. We identified that the differences in BCAA and AAA levels between GDM women and controls, which were not evident during fasting, could be provoked by performing an OGTT.

Targeting lysosomes in human disease: from basic research to clinical applications.

In recent years, accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis. Lysosomal changes and dysfunction have been correlated with the development of numerous diseases. In this review, we interpreted the key biological functions of lysosomes in four areas: cellular metabolism, cell proliferation and differentiation, immunity, and cell death. More importantly, we actively sought to determine the characteristic changes and dysfunction of lysosomes in cells affected by these diseases, the causes of these changes and dysfunction, and their significance to the development and treatment of human disease. Furthermore, we outlined currently available targeting strategies: (1) targeting lysosomal acidification; (2) targeting lysosomal cathepsins; (3) targeting lysosomal membrane permeability and integrity; (4) targeting lysosomal calcium signaling; (5) targeting mTOR signaling; and (6) emerging potential targeting strategies. Moreover, we systematically summarized the corresponding drugs and their application in clinical trials. By integrating basic research with clinical findings, we discussed the current opportunities and challenges of targeting lysosomes in human disease.

YTHDF1 promotes hepatocellular carcinoma progression via activating PI3K/AKT/mTOR signaling pathway and inducing epithelial-mesenchymal transition.

BACKGROUND: N6-methyladenosine (m6A) modification, as the most abundant RNA modification, widely participates in the physiological process and is involved in multiple disease progression, especially cancer. YTH N6-methyladenosine RNA binding protein 1 (YTHDF1) is a pivotal m6A "reader" protein, which has been reported in multiple cancers. However, the role and molecular mechanism of YTHDF1 in HCC are still not fully elucidated. METHODS: Based on various bioinformatics databases, q-RT PCR, western blot, and a tissue microarray containing 90 HCC samples, we examined the expression of YTHDF1 in HCC. Then, we applied the loss-of-function experiments to explore the role of YTHDF1 in HCC by in vitro and in vivo assays. Finally, we performed the gene set enrichment analysis (GSEA) to predict the potential signaling pathway of YTHDF1 involved in HCC and further verified this prediction. RESULTS: YTHDF1 was overexpressed in HCC and associated with HCC grade. Depletion of YTHDF1 markedly impaired the proliferation, migration, invasion, and cell cycle process of HCC cells. Mechanistically, YTHDF1 promoted the growth of HCC cells via activating the PI3K/AKT/mTOR signaling pathway. Moreover, we also demonstrated that the epithelial-mesenchymal transition (EMT) mediated the promoting effect of YTHDF1 on the migration and invasion of HCC cells. CONCLUSIONS: YTHDF1 contributes to the progression of HCC by activating PI3K/AKT/mTOR signaling pathway and inducing EMT.

Gut microbiota in early pregnancy among women with Hyperglycaemia vs. Normal blood glucose.

BACKGROUND: Recent studies suggest that there is a link between the gut microbiota and glucose metabolism. This study aimed to compare the gut microbiota during early pregnancy of women with hyperglycymia to those with normal blood glucose. METHODS: Gut microbial composition was analysed in 22 women with hyperglycaemia and 28 age-matched healthy controls during their first prenatal visits (< 20 weeks) using high throughput sequencing of the V3-V4 region of the 16S ribosomal RNA gene. Hyperglycemia was diagnosed based on the criteria recommended by the International Association of Diabetes and Pregnancy Study Groups in 2010. RESULTS: Women with hyperglycemia in pregnancy (HIP) had significantly lower microbial richness and diversity compared with healthy pregnant women. The proportions of the Firmicutes and Bacteroidetes phyla and the ratio of Firmicutes:Bacteroidetes were not different between the two groups. We observed that individuals with HIP had an increased abundance of Nocardiaceae, Fusobacteriaceae, etc., whereas healthy controls had significantly higher levels of Christensenellaceae, Clostridiales_vadinBB60_group, Coriobacteriaceae, etc. Similarly, levels of the members of the Ruminococcaceae family, including Ruminococcaceae_UCG-014, Ruminococcaceae_UCG-003, and Ruminococcaceae_UCG-002, were significantly reduced in the HIP group and were negatively correlated with HbA1c. HbA1c levels were positively correlated with Bacteroidaceae and Enterobacteriaceae and negatively correlated with Christensenellaceae, etc. CRP was positively correlated with the Bacteroidaceae and Fusobacteriaceae families and the Fusobacterium genus. CONCLUSIONS: Our study revealed that individuals with HIP have gut microbial dysbiosis and that certain bacterial groups are associated with glucose metabolism during pregnancy. Further study is needed to provide new ideas to control glucose by modifying the gut microbiota.

A green approach for the synthesis of novel Ag3PO4/SnO2/porcine bone and its exploitation as a catalyst in the photodegradation of lignosulfonate into alkyl acids.

A novel Ag3PO4/SnO2/porcine bone composite photocatalyst was successfully prepared via an ion exchange method, which can convert lignin derivatives into small molecular acids upon exposure to visible light at room temperature at ambient pressure. The composition characterization, optical absorption properties and photocatalytic activities of the Ag3PO4/SnO2/porcine bone composites were thoroughly investigated. The certain role of each component of the composites in the degradation reaction was discussed: Ag3PO4 acted as the major active component, while SnO2 and porcine bone as cocatalyst contributed to improve the photocatalytic activity and stability of Ag3PO4. The enhanced activity of the Ag3PO4/SnO2/porcine bone composite may be attributed to the synergistic effect including the matched energy band structures of Ag3PO4 and SnO2 for the decrease in the probability of electron-hole recombination and improved performance in the presence of hierarchical porous porcine bone (hydroxyapatite). This paper also analyzed the change of the molecular weight and structure of sodium lignin sulfonate in the photocatalytic reaction and discussed the possible photocatalytic mechanism of the photocatalyst composite, indicating that the benzene rings of guaiacol were oxidized into different alkyl acids (maleic acid, oxalic acid, formic acid and methoxy acetic acid).

Animal Bone Supported SnO2 as Recyclable Photocatalyst for Degradation of Rhodamine B Dye.

SnO2 nanoparticles supported on an animal bone which serves as inexpensive and environment-friendly natural products were developed by a facile hydrothermal approach. As a promising photocatalyst, the novel SnO2/porcine bone material exhibited high photocatalytic activity towards the degradation of rhodamine B (RhB) dye under UV-Vis irradiation. About 97.3% of RhB can be effectively decomposed by the catalysis with the SnO2/porcine bone in 90 min, while only 51.5% of RhB can be degraded by pure SnO2 nanoparticles. Moreover, the photocatalytic activity was incremental with the increase of cycle times in previous five cycles. It is mainly because the photocatalyst which has been used for several times possesses a stronger ability of light absorption and utilization compared to the fresh catalyst according to the results of the characterization and relative experiments. It is noteworthy that the animal bone support can improve the activity for the photocatalyst, which would provide further impetus to alternate synthesis strategies for photocatalysts and make the photocatalysis process faster, less expensive, and more environmentally friendly.

Low serum free thyroxine concentrations associate with increased arterial stiffness in euthyroid subjects: a population-based cross-sectional study.

Some studies suggest that even in euthyroid subjects, thyroid function may affect arteriosclerotic risk factors. We aimed to determine whether thyroid hormones or thyroid autoantibodies are associated with arterial stiffness in middle-aged and elderly Chinese subjects with euthyroidism. A cross-sectional, population-based study was conducted in Nanjing, China. A total of 812 euthyroid subjects (mean age [56.75 ± 8.34] years; 402 men) without vascular disease and major arteriosclerotic risk factors were included. Clinical factors, oral glucose tolerance test results, homeostasis model assessment for insulin resistance (HOMA-IR) results, and serum levels of lipids, free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and thyroid autoantibodies were measured. Arterial stiffness was assessed using brachial-ankle pulse wave velocity (baPWV). In Pearson correlation analyses, baPWV correlated inversely with FT4 (r = -0.146, P < 0.001), but not with FT3 (r = 0.008, P = 0.816) or TSH (r = 0.055, P = 0.118). Subsequently, a multiple stepwise regression analysis revealed a significant and independent association of FT4 with baPWV in euthyroid subjects (ß = -0.076, P = 0.005). After adjusting for potential cardiovascular risk factors, mean diastolic blood pressure (DBP), HOMA-IR, and baPWV levels decreased across increasing FT4 quartiles (DBP, P < 0.001; HOMA-IR, P < 0.001; baPWV, P = 0.003). No difference in baPWV was observed between the positive and the negative thyroid antibody groups (15.23 ± 3.30 m/s vs. 15.73 ± 3.05 m/s, P > 0.05). FT4 levels were inversely associated with arterial stiffness in euthyroid subjects. A prospective study is warranted to validate whether subjects with low-normal FT4 levels have a high incidence of cardiovascular disease.

Visceral adiposity index may be a surrogate marker for the assessment of the effects of obesity on arterial stiffness.

OBJECTIVE: The relationship between obesity and cardiovascular disease (CVD) remains unclear. This study aims to describe the relationship between arterial stiffness and obesity in order to investigate the effects of obesity on CVD. METHODS: We collected data from 5,158 individuals over 40 years of age from a cross-sectional study in Nanjing, China. Anthropometric, demographic, hemodynamic measurements and arterial stiffness measured through brachial-ankle pulse wave velocity (baPWV) were obtained. Subjects were grouped by body mass index (BMI), waist circumference (WC) and visceral adiposity index (VAI), a sex-specific index based on BMI, WC, triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C). RESULTS: The multivariate regression analysis revealed a negative but weak effect of BMI (ß = -0.047, P<0.001) on baPWV, but failed to demonstrate any significant effect of WC on baPWV while VAI was a positive independent indicator of baPWV (ß = 0.023, P = 0.022). The unadjusted baPWV significantly increased across groups with higher obesity categories (P<0.01). Although the positive association was lost after adjustments for confounding factors in the BMI or WC categories (P>0.05), it was still obtained between baPWV and VAI quartile (P<0.01). No differences were observed among the metabolically healthy groups or the metabolically abnormal groups in the BMI and WC categories (P>0.05). However, baPWV significantly increased across groups with higher VAI categories even in the same metabolic category (P<0.01). CONCLUSIONS: This study supports the concept of heterogeneity of metabolic status among individuals within the same obesity range. Obese individuals are at an increased risk of arterial stiffness regardless of their metabolic conditions. VAI may be a surrogate marker for the assessment of obesity and the effects of obesity on arterial stiffness.

Association of high vitamin d status with low circulating thyroid-stimulating hormone independent of thyroid hormone levels in middle-aged and elderly males.

Background. A recent study has reported that high circulating 25-hydroxyvitamin D [25(OH)D] is associated with low circulating thyroid-stimulating hormone (TSH) levels, but only in younger individuals. The goal of the present study was to explore the relationship between vitamin D status and circulating TSH levels with thyroid autoimmunity and thyroid hormone levels taken into consideration in a population-based health survey of middle-aged and elderly individuals. Methods. A total of 1,424 Chinese adults, aged 41-78 years, were enrolled in this cross-sectional study. Serum levels of 25(OH)D, TSH, thyroid hormones, and thyroid autoantibodies were measured. Results. The prevalence of vitamin D insufficiency was 94.29% in males and 97.22% in females, and the prevalence of vitamin D deficiency was 55.61% in males and 69.64% in females. Vitamin D status was not associated with positive thyroid autoantibodies after controlling for age, gender, body mass index, and smoking status. Higher 25(OH)D levels were associated with lower TSH levels after controlling for age, FT4 and FT3 levels, thyroid volume, the presence of thyroid nodule(s), and smoking status in males. Conclusion. High vitamin D status in middle-aged and elderly males was associated with low circulating TSH levels independent of thyroid hormone levels.

Association of calcaneal quantitative ultrasound parameters with metabolic syndrome in middle-aged and elderly Chinese: a large population-based cross-sectional study.

BACKGROUND: The possible association between metabolic syndrome (MS) and bone mineral density (BMD) has been highlighted recently. However, the exact effects of MS on calcaneal quantitative ultrasound (QUS) parameters remains uncertain. The aim of this study was to assess the impact of MS states, different componets of MS, as well as the number of MS componets on QUS. METHODS: A total of 7489 Chinese adults aged 40 years or older in Nanjing were enrolled in this cross-sectional study. MS was defined according to recommendations generated by the International Diabetes Federation (IDF) in 2005. QUS was measured for each participant. RESULTS: The prevalence of MS was 34.6% in men and 42.8% in women (over 40 years old). In postmenopausal women with MS, 25-hydroxyvitamin D[25(OH)D], age adjusted quantitative ultrasound index (QUI) and broadband ultrasound attenuation (BUA) were all lower than those without (p < 0.001, p = 0.023, p = 0.021, respectively), the difference of QUI and BUA disappeared after adjustment for body mass index (BMI) and waist circumference (WC). In stepwise analysis, BMI, WC, high density lipoprotein cholesterol (HDL-C) and fasting plasma glucose (FPG) were related to QUS (p < 0.05). The number of MS components had no influence on QUS. Fragile fracture incidence was higher in women with MS (6.8% VS. 5.3%, P = 0.034). CONCLUSION: Chinese postmenopausal women with MS have worse BMD measured by QUS and more chances to develop osteoporotic fractures than the controls, which partially due to central obesity as well as vitamin D deficiency. People having less central obesity, higher FPG or HDL-C are less likely to have bone mineral loss.

Association between calcaneus quantitative ultrasound (QUS) parameters and thyroid status in middle-aged and elderly Chinese men with euthyroidism: a population-based cross-sectional study.

Although it is generally accepted that thyroid hormones affect bone metabolism, there is little data on the association of thyroid antibodies with bone status. We aimed to investigate the association between thyroid hormones or antibodies and quantitative ultrasound (QUS) parameters. This was a cross-sectional, population-based study conducted in Nanjing, China. A total of 1,001 Chinese men over 40 years were enrolled. We measured free triiodothyronine, free thyroxin (fT4), thyroid-stimulating hormone, anti-thyroid peroxidase (anti-TPO), anti-thyroglobulin, 25-hydroxyvitamin D, and QUS parameters. After adjusting for potential confounders, QUS values decreased from the lowest to highest tertiles of fT4 in euthyroid men [quantitative ultrasound index (QUI) p = 0.002, broadband ultrasound attenuation (BUA) p = 0.000, speed of sound (SOS) p = 0.009, respectively]. Men with high anti-TPO levels (≥200 IU/ml) were found to have lower QUI (p = 0.030), BUA (p = 0.034), and SOS (p = 0.041) values than controls (<200 IU/ml). The prevalence of vitamin D deficiency was significantly higher in individuals with high anti-TPO than those in lower levels (87.5 vs. 59.5 %, p = 0.001). Our results suggest that high fT4 or anti-TPO values are associated with lower QUS parameters. Prospective studies are needed to confirm the precise relationship between thyroid status and osteoporosis.

A Chinese risk score model for identifying postprandial hyperglycemia without oral glucose tolerance test.

BACKGROUND: The aim of the study is to develop a risk score model for identifying postprandial hyperglycemia without oral glucose tolerance tests (OGTT) in Chinese population, and minimize the number of subjects needing further OGTT. METHODS: Multivariable stepwise logistic regression was used to develop risk score models in a derivation cohort (7953 participants without known diabetes). The developed models were verified in a validation cohort (another 1455 subjects without known diabetes). All subjects had completed questionnaires, physical examination and OGTT. Performances of the risk score models were estimated using receiver operating characteristic curves. RESULTS: Two risk score models for screening postprandial hyperglycemia were developed. The simple model used non-invasive risk factors (age, height, weight, waist, systolic blood pressure, pulse, hypertension, dyslipidemia and family history of diabetes mellitus), and the full model contained additional variables [fasting blood glucose (FBG), triglyceride/high density lipoprotein cholesterol] obtainable by invasive laboratory tests. The area under receiver operating characteristic curve (AUC) of simple model was similar to FBG and glycated haemoglobin. The full model has the largest AUC [0.799 (0.789-0.809) and 0.730 (0.702-0.758)] in both derivation and validation cohorts (p < 0.001 compared with simple model, FBG, and glycated haemoglobin). At a cutoff point of 80, the sensitivity, specificity and percentage that needed subsequent OGTT were 75.97, 67.56 and 48.38%, respectively. CONCLUSIONS: We developed a risk score model for screening postprandial hyperglycemia based on routine clinical information. It could effectively identify patients at high-risk for postprandial hyperglycemia and remarkably reduce the number of subjects requiring OGTT.

Insulin Sensitivity and Beta-Cell Function Are Associated with Arterial Stiffness in Individuals without Hypertension.

Aim. We investigated the relationship between brachial-ankle pulse wave velocity (baPWV) and glucose levels, insulin sensitivity, and beta-cell function in Chinese individuals with or without hypertension. Methods. We recruited 3137 nondiabetic individuals whose age, body mass index (BMI), glucose levels, blood pressure (BP), lipids, hemoglobin A1C (HbA1c), baPWV, and insulin levels were measured. Results. In normotensive group, 2 h glucose levels (ß = 0.046, P < 0.001) associated with baPWV, showed a significant increase in patients with NG as compared to those with DM (P = 0.032). The hypertensive group showed no such differences. The Matsuda index (ß = 0.114, P < 0.001) and HOMA- ß (ß = 0.045, P < 0.001) were negatively correlated with baPWV while lnHOMA-IR (ß = 0.196, P = 0.076) and the Quantitative Insulin Sensitivity Check Index (QUICKI) (ß = 0.226, P = 0.046) showed a borderline negative correlation. BaPWV significantly decreased (P = 0.032) with an increase in insulin sensitivity in individuals with both normal BP and glucose tolerance. Conclusions. BaPWV was significantly associated with 2 h glucose levels, insulin sensitivity and beta-cell function in normotensive population, whereas in hypertensive individuals, BP was the dominant factor influencing arterial stiffness. Individuals with abnormal insulin sensitivity in the absence of diabetes and hypertension are also at an increased risk of arterial stiffness.