Hypertriglyceridaemic-waist phenotype and risk of diabetes in people with impaired fasting glucose in primary care: a cohort study

Aim: We aimed to determine the prospective association between baseline triglyceridaemic–waist phenotypes and diabetic mellitus incidence in individuals with impaired fasting glucose seen in primary care. Methods: A cohort of 1101 participants (84.4% of the recruited individuals) with impaired fasting glucose were recruited from three primary care clinics during regular follow-ups to monitor their chronic conditions. Baseline triglyceridaemic–waist phenotypes were divided into four groups: (1) normal waistline and triglyceride level (n = 252); (2) isolated central obesity (n = 518); (3) isolated high triglyceride level (n = 80); and (4) central obesity with high triglyceride level (i.e. hypertriglyceridaemic–waist phenotype) (n = 251). The presence of diabetes at follow-up was determined by fasting plasma glucose (≥ 7.0 mmol/l) and/or 2-h 75-g oral glucose tolerance test (≥ 11.1 mmol/l) and/or HbA1c (47.5 mmol/mol; ≥ 6.5%) according to American Diabetes Association diagnostic criteria. Multivariable Cox proportional hazards regressions were established to assess the impact of different triglyceridaemic–waist phenotypes on time to diabetes onset. Results: After a mean follow-up period of 6.5 months (sd 4.7 months), the number of diabetes cases was significantly higher in the group with hypertriglyceridaemic–waist phenotype (52.2%) compared with the other three phenotype groups (group 1: 28.2%; group 2: 34.6%; group 3: 30.0%). Only the hypertriglyceridaemic–waist phenotype showed an increased risk of developing diabetes (hazard ratio 1.581, 95% CI 1.172–2.134; P = 0.003) compared with the group with normal waistline and triglyceride level after controlling for confounders. Conclusion: The combination of central obesity and hypertriglyceridaemia is associated with > 50% risk of progression to diabetes within 6 months among individuals with impaired fasting glucose seen in primary care

Inhibition of nucleoside transporters in endothelial cells by emodin

Conference Theme: From Cell to TherapyYoung Investigator Award Poster Presentations: CP03Nucleoside transporters play critical roles in endothelial cell functions. Nucleosides are precursor molecules for ATP, nucleic acids, coenzymes and signaling molecules. However, it is known that epithelial cells have a low capacity for de novo synthesis of nucleosides, and they therefore also depend on nucleoside absorption from the extracellular fluid (i.e. salvage pathway). In addition, nucleoside transporters are important in fine tuning the extracellular concentration of adenosine (a vasodilator and anti-inflammatory agent which is ...link_to_OA_fulltextThe 15th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine (ICSM 2011), Hong Kong, 17 September 2011. In Journal of the Hong Kong College of Cardiology, 2011, v. 19 n. 2, p. 72, abstract no. CP

Involvement of plasma membrane monoamine transporter in serotonin uptake in vascular smooth muscle cells

Abstracts for Posters: no. P27link_to_OA_fulltex

Effects of emodin on nucleside transporters in endothelial cells

Poster Presentation - Theme 2: Healthy Aging: no. 2.17The 16th Research Postgraduate Symposium (RPS 2011), Li Ka Shing Faculty of Medicine, the University of Hong Kong, Hong Kong, 7-8 December 2011

Physiological and pharmacological roles of vascular nucleoside transporters

Adenosine modulates various vascular functions such as vasodilatation and anti-inflammation. The local concentration of adenosine in the vicinity of adenosine receptors is fine tuned by 2 classes of nucleoside transporters: equilibrative nucleoside transporters (ENTs) and concentrative nucleoside transporters (CNTs). In vascular smooth muscle cells, 95% of adenosine transport is mediated by ENT-1 and the rest by ENT-2. In endothelial cells, 60%, 10%, and 30% of adenosine transport are mediated by ENT-1, ENT-2, and CNT-2, respectively. In vitro studies show that glucose per se increases the expression level of ENT-1 via mitogen-activating protein kinase-dependent pathways. Similar results have been demonstrated in diabetic animal models. Hypertension is associated with the increased expression of CNT-2. It has been speculated that the increase in the activities of ENT-1 and CNT-2 may reduce the availability of adenosine to adenosine receptors, thereby weakening the vascular functions of adenosine. This may explain why patients with diabetes and hypertension suffer greater morbidity from ischemia and atherosclerosis. No oral hypoglycemic agents can inhibit ENTs, but an exception is troglitazone (a thiazolidinedione that has been withdrawn from the market). ENTs are also sensitive to dihydropyridine-type calcium-channel blockers, particularly nimodipine, which can inhibit ENT-1 in the nanomolar range. Those calcium-channel blockers are noncompetitive inhibitors of ENTs, probably working through the reversible interactions with allosteric sites. The nonsteroidal anti-inflammatory drug sulindac sulfide is a competitive inhibitor of ENT-1. In addition to their original pharmacological actions, it is believed that the drugs mentioned above may regulate vascular functions through potentiation of the effects of adenosine. © 2012 Lippincott Williams & Wilkins, Inc.link_to_subscribed_fulltex

Validation of a nomogram for predicting regression from impaired fasting glucose to normoglycaemia to facilitate clinical decision making

Background. In Hong Kong, fasting plasma glucose (FPG) is the most popular screening test for diabetes mellitus (DM) in primary care. Individuals with impaired fasting glucose (IFG) are commonly encountered. Objectives. To explore the determinants of regression to normoglycaemia among primary care patients with IFG based on non-invasive variables and to establish a nomogram for the prediction of regression from IFG. Methods. This cohort study consisted of 1197 primary care patients with IFG. These subjects were invited to repeat a FPG test and 75-g 2-hour oral glucose tolerance test (2h-OGTT) to determine the glycaemia change. Normoglycaemia was defined as FPG <5.6 mmol/L and 2h-OGTT <7.8 mmol/L. Stepwise logistic regression model was developed to predict the regression to normoglycaemia with non-invasive variables, using a randomly selected training dataset (810 subjects). The model was validated on the remaining testing dataset (387 subjects). Area under the receiver operating characteristic curve (AUC) and Hosmer–Lemeshow test were used to evaluate discrimination and calibration of the model. A nomogram was constructed based on the model. Results. After a mean follow-up period of 6.1 months, 180 subjects (15.0%) had normoglycaemia based on the repeated FPG and 2h-OGTT results at follow-up. Subjects without central obesity or hypertension, with moderate-to-high-level physical activity and a lower baseline FPG level, were more likely to regress to normoglycaemia. The prediction model had acceptable discrimination (AUC = 0.705) and calibration (P = 0.840). Conclusion. The simple-to-use nomogram could facilitate identification of subjects with low risk of progression to DM and thus aid in clinical decision making and resource prioritization in the primary care setting

Ergothioneine shows protective effect on endothelial cells in oxidative stress

Open Access JournalErgothioneine, a chemical richly found in mushroom, has a strong antioxidant effect by removing toxic radical species or chelating metal ions. This effect is mainly studied in simple cell-free systems. Ergothioneine is impermeable to cell membrane and a specific carrier novel organic cation transporter (OCTN)-1 is required for cellular internalization. As OCTN-1 is not …link_to_OA_fulltex

Potential beneficial effect of ergothioneine in protecting endothelial dysfunction

Focused Conference Group: P15 – Endothelium in Health And Disease Potential Beneficial Effect of Ergothioneine in Protecting Endothelial Dysfunction. Paper No. 1649Endothelial function is often impaired in diabetic patients, leading to various pathophysiological processes in cardiovascular diseases. A number of evidence has also demonstrated that reactive oxygen species is one of the major factors for diabetic endothelial dysfunction. Ergothioneine, a chemical rich in mushroom, has been proposed to possess potent antioxidant activities, involving the removal of cell toxic radical species or chelating of metal ions. However, the biological relevance of these findings is unclear because most of the preceding studies were performed in cell-free systems. In this study, we aimed to investigate if ergothioneine can enter endothelial cells and protect endothelial cells against diabetes-induced damage. Human brain microvascular endothelial cells (HBMECs) were used in this study. Ergothioneine is a transport substrate of organic cation transporter novel type 1 (OCTN-1) and our result of RT-PCR and Western blotting showed that OCTN-1 was present in HBMECs. HBMECs were incubated in 5 mM (control) and 25 mM glucose medium (which mimicked the hyperglycemia in diabetes) in the absence of presence of ergothioneine. By means of MTT assay, we found that the viability of HBMECs was significantly lowered in 25 mM glucose condition but this detrimental effect of high glucose could be reduced by ergothioneine, at a concentration as low as 10 nM. In conclusion, our result suggests that ergothioneine can be taken up by endothelial cells and may be a potential protective agent that can protect endothelial cells, particularly in the case of diabetesThe 16th World Congress on Basic and Clinical Pharmacology (WorldPharma2010), Copenhagen, Denmark, 17-23 July 2010. In Basic & Clinical Pharmacology & Toxicology, 2010, v. 107, suppl. 1, p. 58