Deleterious Associations of Sitting Time and Television Viewing Time With Cardiometabolic Risk Biomarkers: Australian Diabetes, Obesity and Lifestyle (AusDiab) study 2004–2005

OBJECTIVE - We examined the associations Of Sitting time and television (TV) Viewing time with continuously measured biomarkers of cardio-metabolic risk in Australian adults

A bi-directional relationship between obesity and health-related quality of life : evidence from the longitudinal AusDiab study

Objective: To assess the prospective relationship between obesity and health-related quality of life, including a novel assessment of the impact of health-related quality of life on weight gain.Design and setting: Longitudinal, national, population-based Australian Diabetes, Obesity and Lifestyle (AusDiab) study, with surveys conducted in 1999/2000 and 2004/2005.Participants: A total of 5985 men and women aged 25 years at study entry.Main outcome measure(s): At both time points, height, weight and waist circumference were measured and self-report data on health-related quality of life from the SF-36 questionnaire were obtained. Cross-sectional and bi-directional, prospective associations between obesity categories and health-related quality of life were assessed.Results: Higher body mass index (BMI) at baseline was associated with deterioration in health-related quality of life over 5 years for seven of the eight health-related quality of life domains in women (all P0.01, with the exception of mental health, P&gt;0.05), and six out of eight in men (all P&lt;0.05, with the exception of role-emotional, P=0.055, and mental health, P&gt;0.05). Each of the quality-of-life domains related to mental health as well as the mental component summary were inversely associated with BMI change (all P&lt;0.0001 for women and P0.01 for men), with the exception of vitality, which was significant in women only (P=0.008). For the physical domains, change in BMI was inversely associated with baseline general health in women only (P=0.023).Conclusions: Obesity was associated with a deterioration in health-related quality of life (including both physical and mental health domains) in this cohort of Australian adults followed over 5 years. Health-related quality of life was also a predictor of weight gain over 5 years, indicating a bi-directional association between obesity and health-related quality of life. The identification of those with poor health-related quality of life may be important in assessing the risk of future weight gain, and a focus on health-related quality of life may be beneficial in weight management strategies.<br /

Associations between cardiorespiratory fitness, physical activity and clustered cardiometabolic risk in children and adolescents: the HAPPY study

Clustering of cardiometabolic risk factors can occur during childhood and predisposes individuals to cardiometabolic disease. This study calculated clustered cardiometabolic risk in 100 children and adolescents aged 10-14 years (59 girls) and explored differences according to cardiorespiratory fitness (CRF) levels and time spent at different physical activity (PA) intensities. CRF was determined using a maximal cycle ergometer test, and PA was assessed using accelerometry. A cardiometabolic risk score was computed as the sum of the standardised scores for waist circumference, blood pressure, total cholesterol/high-density lipoprotein ratio, triglycerides and glucose. Differences in clustered cardiometabolic risk between fit and unfit participants, according to previously proposed health-related threshold values, and between tertiles for PA subcomponents were assessed using ANCOVA. Clustered risk was significantly lower (p < 0.001) in the fit group (mean 1.21 ± 3.42) compared to the unfit group (mean -0.74 ± 2.22), while no differences existed between tertiles for any subcomponent of PA. Conclusion These findings suggest that CRF may have an important cardioprotective role in children and adolescents and highlights the importance of promoting CRF in youth

Decline in Physical Fitness From Childhood to Adulthood Associated With Increased Obesity and Insulin Resistance in Adults

To examine how fitness in both childhood and adulthood is associated with adult obesity and insulin resistance. A prospective cohort study set in Australia in 2004-2006 followed up a cohort of 647 adults who had participated in the Australian Schools Health and Fitness Survey in 1985 and who had undergone anthropometry and cardiorespiratory fitness assessment during the survey. Outcome measures were insulin resistance and obesity, defined as a homeostasis model assessment index above the 75th sex-specific percentile and BMI &ge;30 kg/m^sup 2^, respectively. Lower levels of child cardiorespiratory fitness were associated with increased odds of adult obesity (adjusted odds ratio [OR] per unit decrease 3.0 [95% CI 1.6- 5.6]) and insulin resistance (1.7 [1.1-2.6]). A decline in fitness level between childhood and adulthood was associated with increased obesity (4.5 [2.6-7.7]) and insulin resistance (2.1 [1.5- 2.9]) per unit decline. A decline in fitness from childhood to adulthood, and by inference a decline in physical activity, is associated with obesity and insulin resistance in adulthood. Programs aimed at maintaining high childhood physical activity levels into adulthood may have potential for reducing the burden of obesity and type 2 diabetes in adults.<br /

Lipidomic risk score independently and cost-effectively predicts risk of future type 2 diabetes: results from diverse cohorts

Background: Detection of type 2 diabetes (T2D) is routinely based on the presence of dysglycemia. Although disturbed lipid metabolism is a hallmark of T2D, the potential of plasma lipidomics as a biomarker of future T2D is unknown. Our objective was to develop and validate a plasma lipidomic risk score (LRS) as a biomarker of future type 2 diabetes and to evaluate its cost-effectiveness for T2D screening. Methods: Plasma LRS, based on significantly associated lipid species from an array of 319 lipid species, was developed in a cohort of initially T2D-free individuals from the San Antonio Family Heart Study (SAFHS). The LRS derived from SAFHS as well as its recalibrated version were validated in an independent cohort from Australia--the AusDiab cohort. The participants were T2D-free at baseline and followed for 9197 person-years in the SAFHS cohort (n = 771) and 5930 person-years in the AusDiab cohort (n = 644). Statistically and clinically improved T2D prediction was evaluated with established statistical parameters in both cohorts. Modeling studies were conducted to determine whether the use of LRS would be cost-effective for T2D screening. The main outcome measures included accuracy and incremental value of the LRS over routinely used clinical predictors of T2D risk; validation of these results in an independent cohort and cost-effectiveness of including LRS in screening/intervention programs for T2D. Results: The LRS was based on plasma concentration of dihydroceramide 18:0, lysoalkylphosphatidylcholine 22:1 and triacyglycerol 16:0/18:0/18:1. The score predicted future T2D independently of prediabetes with an accuracy of 76%. Even in the subset of initially euglycemic individuals, the LRS improved T2D prediction. In the AusDiab cohort, the LRS continued to predict T2D significantly and independently. When combined with risk-stratification methods currently used in clinical practice, the LRS significantly improved the model fit (p \u3c 0.001), information content (p \u3c 0.001), discrimination (p \u3c 0.001) and reclassification (p \u3c 0.001) in both cohorts. Modeling studies demonstrated that LRS-based risk-stratification combined with metformin supplementation for high-risk individuals was the most cost-effective strategy for T2D prevention. Conclusions: Considering the novelty, incremental value and cost-effectiveness of LRS it should be used for risk-stratification of future T2D

Rosiglitazone and glimeperide: review of clinical results supporting a fixed dose combination

Type 2 diabetes has become a major burden to the health care systems worldwide. Among the drugs approved for this indication, glimepiride and rosiglitazone have gained substantial importance in routine use. While glimepiride stimulates β-cell secretion and leads to reduction of blood glucose values, rosiglitazone activates PPARγ and improves insulin resistance, at the vascular and metabolically active cells. Therefore, the combination of the two drugs may be an interesting approach to improve glycemic control and lower cardiovascular risk. A fixed combination of both drugs has been approved for clinical use in the US and EU. The combination of glimepiride and rosiglitazone is generally well tolerated and the use of a fixed combination may lead to improved adherence of the patients to their therapy. The purpose of this review is to evaluate the clinical data that have been published on this combination, appearing to represent a convenient way to obtain therapeutic targets in patients with type 2 diabetes mellitus

Novel prokaryotic expression of thioredoxin-fused insulinoma associated protein tyrosine phosphatase 2 (IA-2), its characterization and immunodiagnostic application

Background The insulinoma associated protein tyrosine phosphatase 2 (IA-2) is one of the immunodominant autoantigens involved in the autoimmune attack to the beta-cell in Type 1 Diabetes Mellitus. In this work we have developed a complete and original process for the production and recovery of the properly folded intracellular domain of IA-2 fused to thioredoxin (TrxIA-2ic) in Escherichia coli GI698 and GI724 strains. We have also carried out the biochemical and immunochemical characterization of TrxIA-2icand design variants of non-radiometric immunoassays for the efficient detection of IA-2 autoantibodies (IA-2A). Results The main findings can be summarized in the following statements: i) TrxIA-2ic expression after 3 h of induction on GI724 strain yielded ≈ 10 mg of highly pure TrxIA-2ic/L of culture medium by a single step purification by affinity chromatography, ii) the molecular weight of TrxIA-2ic (55,358 Da) could be estimated by SDS-PAGE, size exclusion chromatography and mass spectrometry, iii) TrxIA-2ic was properly identified by western blot and mass spectrometric analysis of proteolytic digestions (63.25 % total coverage), iv) excellent immunochemical behavior of properly folded full TrxIA-2ic was legitimized by inhibition or displacement of [35S]IA-2 binding from IA-2A present in Argentinian Type 1 Diabetic patients, v) great stability over time was found under proper storage conditions and vi) low cost and environmentally harmless ELISA methods for IA-2A assessment were developed, with colorimetric or chemiluminescent detection. Conclusions E. coli GI724 strain emerged as a handy source of recombinant IA-2ic, achieving high levels of expression as a thioredoxin fusion protein, adequately validated and applicable to the development of innovative and cost-effective immunoassays for IA-2A detection in most laboratories.Fil: Guerra, Luciano Lucas. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Faccinetti, Natalia Ines. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Trabucchi, Aldana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Rovitto, Bruno David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Sabljic, Adriana Victoria. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Poskus, Edgardo. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Iacono, Ruben Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; ArgentinaFil: Valdez, Silvina Noemi. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Instituto de Estudios de la Inmunidad Humoral Prof. Ricardo A. Margni; Argentin

Accelerating Drug Development Using Biomarkers: A Case Study with Sitagliptin, A Novel DPP4 Inhibitor for Type 2 Diabetes

The leveraged use of biomarkers presents an opportunity in understanding target engagement and disease impact while accelerating drug development. For effective integration in drug development, it is essential for biomarkers to aid in the elucidation of mechanisms of action and disease progression. The recent years have witnessed significant progress in biomarker selection, validation, and qualification, while enabling surrogate and clinical endpoint qualification and application. Biomarkers play a central role in target validation for novel mechanisms. They also play a central role in the learning/confirming paradigm, particularly when utilized in concert with pharmacokinetic/pharmacodynamic modeling. Clearly, these attributes make biomarker integration attractive for scientific and regulatory applications to new drug development. In this review, applications of proximal, or target engagement, and distal, or disease-related, biomarkers are highlighted using the example of the recent development of sitagliptin for type 2 diabetes, wherein elucidation of target engagement and disease-related biomarkers significantly accelerated sitagliptin drug development. Importantly, use of biomarkers as tools facilitated design of clinical efficacy trials while streamlining dose focus and optimization, the net impact of which reduced overall cycle time to filing as compared to the industry average

Hubungan Kokurikulum dan Pencapaian Akademik di Kalangan Pelajar Perempuan

In our educational system today, co-curricular activities have not gain its rightful place in our society especially among parents who would put more importance on academic achievements as compared to achievements in co-curricular activities. They view co-curricular activities as a hindrance towards excellent achievements in their children’s examinations. Therefore this study is an attempt to gauge how far it is true that a student who is active in co-curricular activities at school will fare poorly in academic achievements. Research Objectives : follows :- Three main objectives of the study are as 1. To find the extent of female students’ involvement in co-curricular activities. 2. To find out if there is any relationship between being active in co-curricular activities and failure in academic achievements. 3. To compare academic achievement standards between female students who are actively involved in co-curricular activities and those who are not. Research Methods : All 237 Form 4 students of Sekolah Menengah Kebangsaan Sultanah Asma were selected as respondents. They were required to answer questionnaires regarding their persona1 particulars, their family backgrounds and also their degree of involvement in the co-curricular activities. Hypotheses were tested using the SPSS, that is the chi-square analysis and the Pearson Regression analysis. Results : The test showed that there is a significant difference between those students who are actively involved in co-curricular activities and those who are not. There is also a difference in academic achievements between athletes who are hostelites and athletes who are non-hostelites. However, there is no difference in academic achievements between athletes from the lower income-group families and those athletes from the higher income-group families. Therefore, this study rejects the null hypotheses and accepts the alternative hypotheses. Active involvement in the co-curricular activities has negative effects on academic achievements among female students