Gynostemma pentaphyllum

Aims. To evaluate the effect of the traditional Vietnamese herb Gynostemma pentaphyllum tea on insulin sensitivity in drug-naïve type 2 diabetic patients. Methods. Patients received GP or placebo tea 6 g daily for four weeks and vice versa with a 2-week wash-out period. At the end of each period, a somatostatin-insulin-glucose infusion test (SIGIT) was performed to evaluate the insulin sensitivity. Fasting plasma glucose (FPG), HbA1C, and oral glucose tolerance tests and insulin levels were measured before, during, and after the treatment. Results. FPG and steady-state plasma glucose (SIGIT mean) were lower after GP treatment compared to placebo treatment (P<0.001). The levels of FPG in the control group were slightly reduced to 0.2±1.5 versus 1.9±1.0 mmol/L in GP group (P<0.001), and the effect on FPG was reversed after exchanging treatments. The glycometabolic improvements were achieved without any major change of circulating insulin levels. There were no changes in lipids, body measurements, blood pressure, and no reported hypoglycemias or acute adverse effects regarding kidney and liver parameters. Conclusion. The results of this study suggested that the GP tea exerted antidiabetic effect by improving insulin sensitivity

Human neuropeptide Y signal peptide gain-of-function polymorphism is associated with increased body mass index: possible mode of function

Neuropeptide Y (NPY) has been implicated in the control of food intake and energy balance based on many observations in animals. We have studied single nucleotide polymorphisms (SNPs) within the regulatory and coding sequences of the human NPY gene. One variant (1128 T>C), which causes an amino acid change from leucine to proline at codon 7 in the signal peptide of NPY, was associated with increased body mass index (BMI) in two separate Swedish populations of normal and overweight individuals. In vitro transcription and translation studies indicated the unlikelihood that this signal peptide variation affects the site of cleavage and targeting or uptake of NPY into the endoplasmic reticulum (ER). However, the mutant, and to a lesser extent the wild-type, signal peptide by themselves markedly potentiated NPY-induced food intake, as well as hypothalamic NPY receptor signaling. Our findings in humans strongly indicate that the NPY signaling system is implicated in body weight regulation and suggest a new and unexpected functional role of a signal peptide

Особливості державного регулювання інвестиційно-інноваційної діяльності, в сфері екології

BACKGROUND: Particulate matter (PM) air pollution is a human lung carcinogen; however, the components responsible have not been identified. We assessed the associations between PM components and lung cancer incidence. METHODS: We used data from 14 cohort studies in eight European countries. We geocoded baseline addresses and assessed air pollution with land-use regression models for eight elements (Cu, Fe, K, Ni, S, Si, V and Zn) in size fractions of PM2.5 and PM10. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effect models for meta-analysis. RESULTS: The 245,782 cohort members contributed 3,229,220 person-years at risk. During follow-up (mean, 13.1 years), 1878 incident cases of lung cancer were diagnosed. In the meta-analyses, elevated hazard ratios (HRs) for lung cancer were associated with all elements except V; none was statistically significant. In analyses restricted to participants who did not change residence during follow-up, statistically significant associations were found for PM2.5 Cu (HR, 1.25; 95% CI, 1.01-1.53 per 5 ng/m(3)), PM10 Zn (1.28; 1.02-1.59 per 20 ng/m(3)), PM10 S (1.58; 1.03-2.44 per 200 ng/m(3)), PM10 Ni (1.59; 1.12-2.26 per 2 ng/m(3)) and PM10 K (1.17; 1.02-1.33 per 100 ng/m(3)). In two-pollutant models, associations between PM10 and PM2.5 and lung cancer were largely explained by PM2.5 S. CONCLUSIONS: This study indicates that the association between PM in air pollution and lung cancer can be attributed to various PM components and sources. PM containing S and Ni might be particularly important

Perspectives of Patients with Insulin-Treated Type 1 and Type 2 Diabetes on Hypoglycemia: Results of the HAT Observational Study in Central and Eastern European Countries

INTRODUCTION: The aim of this study was to determine the level of awareness of hypoglycemia, the level of fear for hypoglycemia, and the response to hypoglycemic events among insulin-treated diabetes patients from Central and Eastern Europe (CEE). The impact of hypoglycemia on the use of healthcare resources and patient productivity was also assessed. METHODS: This was a multicenter, non-interventional, two-part, patient self-reported questionnaire study that comprised both a retrospective cross-sectional evaluation and a prospective observational evaluation. Study participants were insulin-treated adult patients with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) from CEE. RESULTS: Most patients (85.4% T1DM and 83.6% T2DM) reported normal hypoglycemia awareness. The median hypoglycemia fear score was 5 out of 10 for T1DM and 4 out of 10 for T2DM patients. Patients increased glucose monitoring, consulted a doctor/nurse, and/or reduced the insulin dose in response to hypoglycemia. As a consequence of hypoglycemia, patients took leave from work/studies or arrived late and/or left early. Hospitalization was required for 31 (1.2%) patients with T1DM and 66 (2.1%) patients with T2DM. CONCLUSION: Hypoglycemia impacts patients' personal and social functioning, reduces productivity, and results in additional costs, both direct (related to increased use of healthcare resources) and indirect (related to absenteeism. FUNDING: Novo Nordisk

Functional and genetic analysis in type 2 diabetes of Liver X receptor alleles – a cohort study

<p>Abstract</p> <p>Background</p> <p>Liver X receptor alpha <it>(LXRA</it>) and beta (<it>LXRB</it>) regulate glucose and lipid homeostasis in model systems but their importance in human physiology is poorly understood. This project aimed to determine whether common genetic variations in <it>LXRA </it>and <it>LXRB </it>associate with type 2 diabetes (T2D) and quantitative measures of glucose homeostasis, and, if so, reveal the underlying mechanisms.</p> <p>Methods</p> <p>Eight common single nucleotide polymorphisms in <it>LXRA </it>and <it>LXRB </it>were analyzed for association with T2D in one French cohort (N = 988 cases and 941 controls), and for association with quantitative measures reflecting glucose homeostasis in two non-diabetic population-based samples comprising N = 697 and N = 1344 adults. Investigated quantitative phenotypes included fasting plasma glucose, serum insulin, and HOMA_IRas measure of overall insulin resistance. An oral glucose tolerance test was performed in N = 1344 of adults. The two alleles of the proximal <it>LXRB </it>promoter, differing only at the SNP rs17373080, were cloned into reporter vectors and transiently transfected, whereupon allele-specific luciferase activity was measured. rs17373080 overlapped, according to <it>in silico </it>analysis, with a binding site for Nuclear factor 1 (NF1). Promoter alleles were tested for interaction with NF1 using direct DNA binding and transactivation assays.</p> <p>Results</p> <p>Genotypes at two <it>LXRB </it>promoter SNPs, rs35463555 and rs17373080, associated nominally with T2D (P values 0.047 and 0.026). No <it>LXRA </it>or <it>LXRB </it>SNP associated with quantitative measures reflecting glucose homeostasis. The rs17373080 C allele displayed higher basal transcription activity (P value < 0.05). The DNA-mobility shift assay indicated that oligonucleotides corresponding to either rs17373080 allele bound NF1 transcription factors in whole cell extracts to the same extent. Different NF1 family members showed different capacity to transactivate the <it>LXRB </it>gene promoter, but there was no difference between promoter alleles in NF1 induced transactivation activity.</p> <p>Conclusion</p> <p>Variations in the <it>LXRB </it>gene promoter may be part of the aetiology of T2D. However, the association between <it>LXRB </it>rs35463555 and rs17373080, and T2D are preliminary and needs to be investigated in additional larger cohorts. Common genetic variation in <it>LXRA </it>is unlikely to affect the risk of developing T2D or quantitative phenotypes related to glucose homeostasis.</p

Shikonin Increases Glucose Uptake in Skeletal Muscle Cells and Improves Plasma Glucose Levels in Diabetic Goto-Kakizaki Rats

Glucose is the most common substrate for energy metabolism. Despite the varying demands for glucose, the body needs to regulate its internal environment and maintain a constant and stable condition. Glucose homeostasis requires harmonized interaction between several tissues, achieving equilibrium between glucose output and uptake. In this thesis we aimed to investigate factors modulating glucose homeostasis in a rat model of type 2 diabetes, the Goto-Kakizaki (GK) rat. In addition, we investigated sex differences in hepatic carbohydrate and lipid metabolism in healthy rats. In Paper I, three-week but not three-day treatment with a Southeast Asian herb, Gynostemma pentaphyllum (GP), significantly reduced plasma glucose (PG) levels in GK rats. An intra-peritoneal glucose tolerance test (IPGTT) was significantly improved in GP-treated compared to placebo-treated group. In the GP treated rats, the glucose response in an intra-peritoneal pyruvate tolerance test was significantly lower, indicating decreased gluconeogenesis, and hepatic glucose output (HGO) was reduced. GP-treatment significantly reduced hepatic glycogen content, but not glycogen synthase activity. The study provides evidence that the GP extract exerted anti-diabetic effect in GK rats, reducing PG levels and HGO, suggesting that GP improves the hepatic insulin sensitivity by suppressing gluconeogenesis. In Paper II, shikonin, a naphthoquinone derived from the Chinese plant Lithospermum erythrorhizon, increased glucose uptake in L6 myotubes, but did not phosphorylate Akt. Furthermore we found no evidence for the involvement of AMP activated protein kinase (AMPK) in shikonin induced glucose uptake. Shikonin increased the intracellular levels of calcium in these cells and stimulated the translocation of GLUT4 from intracellular vesicles to the cell surface in L6 myotubes. In GK rats treated with shikonin once daily for 4 days, PG levels were significantly decreased. In an insulin sensitivity test, the absolute PG levels were significantly lower in the shikonin-treated rats. These findings suggest that shikonin increases glucose uptake in muscle cells via an insulin-independent pathway dependent on calcium. In Paper III, GK and control Wistar rats were injected daily for up to 4 weeks with either a non-hematopoietic erythropoietin analog ARA290 or with placebo. PG levels in GK but not Wistar rats were significantly lower in ARA290-treated compared to placebo. After 2 and 4 weeks, the IPGTT was significantly improved in ARA290 treated GK rats. In insulin and pyruvate tolerance tests, glucose responses were similar in ARA290 and placebo groups. In isolated GK rat islets, glucose-stimulated insulin release was two-fold higher and islet intracellular calcium concentrations in response to several secretagogues were significantly higher in ARA290-treated than in placebo-treated GK rats. These findings indicate that treatment with ARA290 significantly improved glucose tolerance in diabetic GK rats, most likely due to improvement of insulin release. In Paper IV, sex differences in hepatic carbohydrate and lipid metabolism were characterized in healthy rats. No sex-differences were observed regarding hepatic triglyceride content, fatty acid oxidation rates or insulin sensitivity. Male rats had higher ratios of insulin to glucagon levels, increased hepatic glycogen content, a lower degree of AMPK phosphorylation, a higher rate of glucose production and higher expression levels of gluconeogenic genes, as compared to female rats. A sex-dependent response to mild starvation was observed with males being more sensitive. In conclusion, sex-differences reflect a higher capacity of the healthy male rat liver to respond to increased energy demands. Key words: glucose homeostasis, type 2 diabetes, GK rats, L6 myotubes, hepatic glucose output, insulin sensitivity, sex differences

Quality of interaction between primary health-care providers and patients with type 2 diabetes in Muscat, Oman: an observational study

BACKGROUND: A good patient-physician interaction is particularly important in chronic diseases like diabetes. There are so far no published data regarding the interaction between the primary health-care providers and patients with type 2 diabetes in Oman, where diabetes is a major and growing health problem. This study aimed at exploring how health-care providers interact with patients with type 2 diabetes at primary health-care level in Muscat, Oman, focusing on the consultation environment, and some aspects of care and information. METHODS: Direct observations of 90 consultations between 23 doctors and 13 diabetes nurses concerned with diabetes management during their consultations with type 2 diabetes patients in six primary health-care centres in the Muscat region, using checklists developed from the National Diabetes Guidelines. Consultations were assessed as optimal if more than 75% of observed aspects were fulfilled and sub-optimal if less than 50% were fulfilled. RESULTS: Overall 52% of the doctors' consultations were not optimal. Some important aspects for a positive consultation environment were fulfilled in only about half of the doctors' consultations: ensuring privacy of consultation (49%), eye contact (49%), good attention (52%), encouraging asking questions (47%), and emphasizing on the patients' understanding of the provided information (52%). The doctors enquired about adverse effects of anti-diabetes drugs in less than 10% of consultations. The quality of the nurses' consultations was sub-optimal in about 75% of 85 consultations regarding aspects of consultation environment, care and information. CONCLUSION: The performance of the primary health-care doctors and diabetes nurses needs to be improved. The role of the diabetes nurses and the teamwork should be enhanced. We suggest a multidisciplinary team approach, training and education to the providers to upgrade their skills regarding communication and care. Barriers to compliance with the guidelines need to be further explored. Improving the work situation mainly for the diabetes nurses and further improvement in the organizational efficiency of diabetes services such as lowering the number of patients in diabetes clinic, are suggested

Patient-provider interaction from the perspectives of type 2 diabetes patients in Muscat, Oman: a qualitative study

<p>Abstract</p> <p>Background</p> <p>Patients' expectations and perceptions of the medical encounter and interactions are important tools in diabetes management. Some problems regarding the interaction during encounters may be related to a lack of communication skills on the part of either the physician or the patient.</p> <p>This study aimed at exploring the perceptions of type 2 diabetes patients regarding the medical encounters and quality of interactions with their primary health-care providers.</p> <p>Methods</p> <p>Four focus group discussions (two women and two men groups) were conducted among 27 purposively selected patients (13 men and 14 women) from six primary health-care centres in Muscat, Oman. Qualitative content analysis was applied.</p> <p>Results</p> <p>The patients identified some weaknesses regarding the patient-provider communication like: unfriendly welcoming; interrupted consultation privacy; poor attention and eye contact; lack of encouraging the patients to ask questions on the providers' side; and inability to participate in medical dialogue or express concerns on the patients' side. Other barriers and difficulties related to issues of patient-centeredness, organization of diabetes clinics, health education and professional competency regarding diabetes care were also identified.</p> <p>Conclusion</p> <p>The diabetes patients' experiences with the primary health-care providers showed dissatisfaction with the services. We suggest appropriate training for health-care providers with regard to diabetes care and developing of communication skills with emphasis on a patient-centred approach. An efficient use of available resources in diabetes clinics and distributing responsibilities between team members in close collaboration with patients and their families seems necessary. Further exploration of the providers' work situation and barriers to good interaction is needed. Our findings can help the policy makers in Oman, and countries with similar health systems, to improve the quality and organizational efficiency of diabetes care services.</p

Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review.

BACKGROUND: Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. METHODS: A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. FINDINGS: This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. CONCLUSIONS: There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease.This work was funded by the National Institute for Health and Care Excellence (NICE), invitation to tender reference DDER 42013, and supported by the National Institute for Health Research School for Public Health Research. The scope of the work was defined by NICE and the protocol was agreed with NICE prior to the start of work. The funders had no role in data analysis, preparation of the manuscript or decision to publish.This is the final version of the article. It first appeared from PLOS via http://dx.doi.org/10.1371/journal.pone.014440