Perspectives of CB1 Antagonist in Treatment of Obesity: Experience of RIO-Asia

Rimonabant, a selective cannabinoid-1 (CB1) receptor antagonist, has been shown to reduce weight and enhance improvements in cardiometabolic risk parameters in Western populations. This study assessed these effects of rimonabant in Asian population. A total of 643 patients (BMI 25 kg/m2 or greater without diabetes) from China, Republic of Korea, and Taiwan were prescribed a hypocaloric diet (600 kcal/day deficit) and randomized to rimonabant 20 mg (n = 318) or placebo (n = 325) for 9months. The primary efficacy variable was weight change from baseline after 9 months of treatment. Results showed that rimonabant group lost more weight than placebo, (LSM ± SEM of −4.7 ± 0.3 kg vs. −1.7 ± 0.3 kg, P < .0001). The 5% and 10% responders were 2 or 3 folds more in the rimonabant group (53.0% vs. 20.0% and 21.5% vs. 5.7%, resp.) (P < .0001). Rimonabant also significantly increased HDL-cholesterol, decreased triglycerides and waist circumference,by 7.1%, 10.6%, and 2.8 cm, respectively (P < .0001). This study confirmed the comparable efficacy and safety profile of rimonabant in Asian population to Caucasians. Owing to the recent suspension of all the CB1 antagonists off the pharmaceutical market for weight reduction in Europe and USA, a perspective in drug discovery for intervening peripheral CB1 receptor in the management of obesity is discussed

Five Blood Pressure Loci Identified by an Updated Genome-Wide Linkage Scan: Meta-Analysis of the Family Blood Pressure Program

Background A preliminary genome-wide linkage analysis of blood pressure in the Family Blood Pressure Program (FBPP) was reported previously. We harnessed the power and ethnic diversity of the final pooled FBPP dataset to identify novel loci for blood pressure thereby enhancing localization of genes containing less common variants with large effects on blood pressure levels and hypertension. Methods We performed one overall and 4 race-specific meta-analyses of genome-wide blood pressure linkage scans using data on 4,226African-American, 2,154 Asian, 4,229 Caucasian, and 2,435 Mexican- American participants (total N = 13,044). Variance components models were fit to measured (raw) blood pressure levels and two types of antihypertensive medication adjusted blood pressure phenotypes within each of 10 subgroups defined by race and network. A modified Fisher's method was used to combine the P values for each linkage marker across the 10 subgroups. Results Five quantitative trait loci (QTLs) were detected on chromosomes 6p22.3, 8q23.1, 20q13.12, 21q21.1, and 21q21.3 based on significant linkage evidence (defined by logarithm of odds (lod) score ≥3) in at least one meta-analysis and lod scores ≥1 in at least 2 subgroups defined by network and race. The chromosome 8q23.1 locus was supported by Asian-, Caucasian-, and Mexican-American-specific meta-analyses. Conclusions The new QTLs reported justify new candidate gene studies. They may help support results from genome-wide association studies (GWAS) that fall in these QTL regions but fail to achieve the genome-wide significance. American Journal of Hypertension advance online publication 9 December 2010;doi:10.1038/ajh.2010.23

Lower intake of magnesium and dietary fiber increases the incidence of type 2 diabetes in Taiwanese

Several studies have indicated an inverse association between the incidence of diabetes mellitus and magnesium and dietary fiber intake. Few studies have examined both of these associations together, not to mention in Asian populations with prospective study design. We therefore aimed to study how dietary magnesium and fiber intake levels affect diabetes incidence separately or in combination, in a prospective study in Taiwan. Methods: The study subjects were recruited for a longitudinal study, CardioVascular Disease risk FACtor Two-township Study cycle 2 from November 1990. Data from complete baseline information on dietary and biochemical profile and at least one additional follow-up visit were gathered on a total of 1604 healthy subjects aged 30 years and over. Cox proportional hazard model was used to study the association between diabetes incidence and dietary magnesium and fiber intake level estimated from a food frequency questionnaire. Results: A total of 141 diabetes mellitus events were identified and confirmed during the 4.6 years of follow-up (7365.1 person-years). A significantly higher diabetes risk was observed for people in the lowest quintile of total dietary fiber intake (hazard ratio = 2.04; 95% CI = 1.17–3.53) and magnesium intake (hazard ratio = 2.61; 95% CI = 1.42–4.79) compared with the highest quintile after adjusting for traditional cardiovascular disease risk factors. Similar inverse associations for total dietary fiber were also shown for vegetable fiber and fruit fiber. Conclusion: Lower magnesium, lower total dietary fiber intake, or lower intake of both was associated with higher risk of diabetes in the Taiwanese population. Clinical trials are required to confirm the protective effects of the adequate intake of fiber, magnesium, and/or their combination

National trends in anti-diabetic treatment in Taiwan, 2000–2009

The impact of the introduction of newer anti-diabetic agents on the treatment pattern in the booming diabetic population remains unclear. We examined the patterns and temporal trends of anti-diabetic drug use in Taiwan, with particular emphasis on combination therapy. Methods: We searched the Taiwan National Health Insurance Database during 2000–2009 to identify outpatient prescriptions of anti-diabetic drugs, including human insulins and insulin analogues, sulfonylureas, glinides, metformin, thiazolidinediones, alpha-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors. Glucose-lowering treatments were classified according to pattern (oral agents only, insulins only, and oral agents and insulins combined) and a number of different classes of anti-diabetic drugs. Insulin therapy and combination therapy with two oral anti-diabetic drugs (OAD) were further classified according to individual drug combination patterns. Results: Although metformin remained the mainstay of anti-diabetic treatment, patients receiving combination therapy of oral glucose-lowering agents, either with or without insulin, significantly increased, from approximately 40% in 2000 to 60% in 2009, particularly in relation to the newer agents, including glinides, alpha-glucosidase inhibitors, and long-acting insulin analogues. Use of sulfonylureas and thiazolidinediones decreased substantially. For insulin therapy, the most commonly prescribed drugs were premix insulin analogues and basal insulin analogues, accounting for one-third of total insulin prescriptions in 2009. Conclusion: We found an increasing complexity of anti-diabetic therapy during the past decade in Taiwan. Further studies are needed to evaluate whether this treatment pattern will lead to improved clinical outcomes in terms of cost-effectiveness

The use of dehydroepiandrosterone-treated rats is not a good animal model for the study of metabolic abnormalities in polycystic ovary syndrome

Objective: Hyperandrogenism is the hallmark of polycystic ovary syndrome (PCOS). The use of dehydroepiandrosterone (DHEA)-treated rats is thought to be a suitable animal model to study PCOS. In the present study, we assessed the severity of reproductive and metabolic abnormalities in DHEA-treated rats. Material and methods: Immature female Sprague–Dawley rats were divided into control and DHEA-treated groups. Reproductive parameters including estrus cycle and sex hormones were measured after sexual maturity. Adiposity, insulin sensitivity, and plasma lipid profiles were analyzed to assess metabolic profiles. After sacrifice, the insulin signaling pathway and lipogenic genes were analyzed by immunoblotting and polymerase chain reaction, respectively. Results: An abnormal estrus cycle was observed in the DHEA-treated rats. DHEA treatment also increased plasma testosterone levels and caused multiple cystic follicle formation, which is compatible with the definition of PCOS. There were no significant changes in fasting glucose, fasting insulin, plasma lipid profiles, and blood pressure levels. The adiposity of the DHEA-treated rats was also lower than in the control rats. Moreover, glucose tolerance and insulin sensitivity were only mildly impaired in the DHEA-treated rats after oral glucose tolerance and insulin tolerance tests, even though insulin signaling in skeletal muscles was decreased in the DHEA-treated group. Conclusion: DHEA-treated rats had reproductive abnormalities which mimicked symptoms of human PCOS. In metabolic parameters, DHEA treatment did not show insulin resistance in the female rats, suggesting that the use of DHEA-treated rats is not a good animal model for the study of metabolic abnormalities in PCOS. Keywords: Polycystic ovary syndrome, DHEA, Insulin sensitivit

A Longitudinal Study of Growth Patterns in Schoolchildren in One Taipei District II: Sitting Height, Arm Span, Body Mass Index and Skinfold Thickness

It has been suggested that longitudinal rather than cross-sectional growth standards be used to assess individual growth patterns. Thus, the aim of this study was to follow boys and girls throughout their pubertal years, so that a mixed longitudinal growth curve of height, weight, sitting height, arm span, skinfold thickness, body mass index (BMI), and the ratio of sitting height or arm span to stature, could be obtained. Methods: A defined group of 1,139 healthy schoolchildren (570 boys and 569 girls) from the Shih-Pai district of Taipei were followed longitudinally for 4 years. Anthropometric measurements of height, weight, sitting height, arm span, skinfold thickness, and BMI, were obtained for each child. Results: Peak sitting-height velocities of 6.1 cm/year (boys) and 6.3 cm/year (girls) were seen at 8.5 years. The second peak of sitting-height velocity occurred at a mean age of 12.5 years for boys and 11.5 years for girls. Sitting-height velocity for the whole year covering the second peak was 4.6 cm in boys and 3.2 cm in girls. Peak arm-span velocity was seen at 13.5 years for boys and 8.5 years for girls, and arm-span velocity for the whole year covering this peak was 8.4 cm/year for boys and 8.1 cm/year for girls. Conclusion: These data provide growth patterns for Chinese children aged 8–18 years living in a Taipei district, with percentile charts for sitting height, arm span, BMI, and skinfold thickness