Jun Goo Kang

Anti-Obesity Drugs: A Review about Their Effects and Safety

The current recommendations for the treatment of obese people include increased physical activity and reduced calories intake. When the behavioral approach is not sufficient, a pharmacologic treatment is recommended. In past years, numerous drugs have been approved for the treatment of obesity; however, most of them have been withdrawn from the market because of their adverse effects. In fact, amphetamine, rimonabant and sibutramine licenses have been withdrawn due to an increased risk of psychiatric disorders and non-fatal myocardial infarction or stroke. Even if orlistat is not as effective as other drugs in reducing body weight, orlistat is presently the only available choice for the treatment of obesity because of its safety for cardiovascular events and positive effects on diabetic control. Hopefully, more effective and better tolerated anti-obesity drugs will be developed through an improved understanding of the multiple mechanisms and complex physiological systems targeting appetite.

Randomized controlled trial to investigate the effects of a newly developed formulation of phentermine diffuse-controlled release for obesity

Aim: To evaluate the efficacy and safety of a newly developed formulation of phentermine diffuse‐controlled release (DCR) in patients with obesity.

Is central obesity a better discriminator of the risk of hypertension than body mass index in ethnically diverse populations

Objective To compare the performance of body mass index (BMI) against waist circumference, waist: hip ratio (WHR) and waist: height ratio in the discrimination of hypertension in ethnically diverse populations. Methods Meta-analysis of 19 cross-sectional studies. Main outcome measures Discrimination of hypertension (SBP/DBP ≥ 140/90 mmHg) was adjudicated from Receiver Operating Characteristic curves; optimum thresholds were defined as those that maximized sensitivity plus specificity. Results Irrespective of which measure of overweight was used, the strength of the association with blood pressure was consistently greater among Asians compared with Caucasians or Pacific Islanders; however, in all regions, and for all anthropometric measures, the increment in blood pressure, and the additional risk of hypertension, were broadly similar for the same relative increment in each of the four measures. Optimum thresholds varied by region; WHR was the most consistent between the regions, with thresholds of 0.92–0.94 for men and 0.80–0.88 for women. No anthropometric variable was systematically better than others at the discrimination of hypertension. Conclusions Blood pressure is similarly associated with each of the four measures of overweight chosen, but the associations were stronger among Asians. WHR has advantages in terms of consistency of thresholds for hypertension across ethnic groups in the Asia–Pacific.

Insulin dose titration system in diabetes patients using a short messaging service automatically produced by a knowledge matrix.

BACKGROUNDnWe designed a system for diabetes patients treated with glargine, a long-acting insulin, to make an automatic adjustment of insulin dose based on glucose level data and to provide the patients with the needed insulin dose by using a short message service (SMS). We also compared diabetes patients who used our system with patients who received the conventional titration scheme.nnnMETHODSnIncluded were 100 type 2 diabetes patients whose blood glucose was suboptimally controlled on their previous antidiabetes treatment. Each participant was assigned to either the intervention or control group, each with 50 patients, using adaptive randomization. We applied our system to the intervention group for 12 weeks, whereas the control group received a conventional titration scheme, seeking a target fasting blood glucose of <120 mg/dL.nnnRESULTSnThe fasting and postprandial glucose levels of the intervention group declined earlier than those of the control group. Lastly, a greater (P = 0.023) reduction in hemoglobin A(1C) from baseline to the end point was observed in the intervention group (from 9.8 +/- 1.3% to 7.4 +/- 0.7%) than in the control group (from 9.8 +/- 1.2% to 7.8 +/- 0.8%). The incidence of symptomatic, asymptomatic, and nocturnal hypoglycemia was similar in both groups. There was a small increase in body weight from baseline to the end point with both the intervention (2.4 +/- 3.0 kg) and control (2.2 +/- 2.8 kg) groups.nnnCONCLUSIONSnThis study demonstrated that SMS based on our specialized Internet-supported system is an effective and safe approach to long-acting insulin dose adjustments in patients with type 2 diabetes.

The discrimination of dyslipidaemia using anthropometric measures in ethnically diverse populations of the Asia-Pacific Region: The Obesity in Asia Collaboration

Dyslipidaemia is a major risk factor for cardiovascular disease and is only detectable through blood testing, which may not be feasible in resource‐poor settings. As dyslipidaemia is commonly associated with excess weight, it may be possible to identify individuals with adverse lipid profiles using simple anthropometric measures. A total of 222u2003975 individuals from 18 studies were included as part of the Obesity in Asia Collaboration. Linear and logistic regression models were used to assess the association between measures of body size and dyslipidaemia. Body mass index, waist circumference, waistu2003:u2003hip ratio (WHR) and waistu2003:u2003height ratio were continuously associated with the lipid variables studied, but the relationships were consistently stronger for triglycerides and high‐density lipoprotein cholesterol. The associations were similar between Asians and non‐Asians, and no single anthropometric measure was superior at discriminating those individuals at increased risk of dyslipidaemia. WHR cut‐points of 0.8 in women and 0.9 in men were applicable across both Asians and non‐Asians for the discrimination of individuals with any form of dyslipidaemia. Measurement of central obesity may help to identify those individuals at increased risk of dyslipidaemia. WHR cut‐points of 0.8 for women and 0.9 for men are optimal for discriminating those individuals likely to have adverse lipid profiles and in need of further clinical assessment.

Dose-related cytoprotective effect of α-lipoic acid on hydrogen peroxide-induced oxidative stress to pancreatic beta cells

α-Lipoic acid (α-LA), an antioxidant used for diabetic polyneuropathy, was reported to induce AMP-activated protein kinase activation and reductions in insulin secretion in pancreatic beta-cells at high concentrations (≥ 500 µmol/l). This study investigated whether α-LA has a protective role under oxidative stress in beta-cells and its effect is dose-related. In INS-1 cells treated with α-LA (150-1200 µmol/l) for 24 h, α-LA itself (≥300 µmol/l) induced apoptotic death dose-dependently. However, pre-treatment with 150 and 300 µmol/l α-LA reduced the hydrogen peroxide-induced apoptosis in INS-1 cells and isolated islets. α-LA alleviated hydrogen peroxide-induced reactive oxygen species production, mitochondrial membrane depolarization and c-JNK activation in beta-cells. α-LA induced phosphoinositide 3-kinase-dependent Akt phosphorylation in INS-1 cells. While α-LA is harmful to beta-cells at high concentrations in vitro, it has potential cytoprotective effects on beta-cells under oxidative stress as in diabetes by its antioxidant properties and possibly by Akt phosphorylation at clinically relevant concentrations.

The estimation of cardiovascular risk factors by body mass index and body fat percentage in Korean male adults.

The aim of the study was to assess cardiovascular risk in men with high body fat percentage (BF%) and normal body mass index (BMI) and men with normal BF% and high BMI. This study was a cross-sectional study using data on 5534 Korean male adults. Body mass index, BF%, and waist circumference were measured as adiposity indices. Bioelectrical impedance analysis was used for measuring BF%. Blood pressure, fasting plasma glucose, total cholesterol, triglyceride, and high-density lipoprotein cholesterol were measured routinely. Information regarding alcohol consumption, smoking, exercise, and past/current medical history was obtained by structured questionnaires. Subjects were categorized into 4 groups by means of BMI and BF% (group 1, BMI <25 kg/m(2) and BF% <25%; group 2, BMI <25 kg/m(2) and BF% > or =25%; group 3, BMI > or =25 kg/m(2) and BF% <25%; group 4, BMI > or =25 kg/m(2) and BF% > or =25%). Cardiovascular risk factors (CVRFs) such as high blood pressure, hyperglycemia, and dyslipidemia were estimated in each group. As might be expected, the prevalences of high blood pressure, hyperglycemia, and dyslipidemia were lowest in group 1 and were highest in group 4. Multivariate analyses showed that subjects in group 2 or group 4 had a 1.8 times increased risk of clustering of 2 or more CVRFs compared with subjects in group 1 (P < .001). The adjusted odds ratio (1.15; 95% confidence interval, 0.94-1.40) of subjects in group 3 on clustering of 2 or CVRFs was not significantly increased (P = .180). High BF% was related to increase of cardiovascular risk regardless of the level of BMI in Korean men. However, cardiovascular risk of men with high BMI without high BF% was not significantly increased.

Mechanisms of adipose tissue redistribution with rosiglitazone treatment in various adipose depots.

Treatment with thiazolidinediones (TZDs) improves glucose homeostasis by increasing insulin sensitivity, but it also leads to weight gain. Our hypothesis was that, in individual adipose depots, there is depot specificity for lipid storage and energy expenditure genes after TZD treatment. After 5 weeks of rosiglitazone treatment on Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an animal model of type 2 diabetes mellitus with obesity, and Long-Evans Tokushima Otsuka rats as controls, we measured changes in lipid storage and energy expenditure gene expression in various adipose depots, such as mesenteric and nonmesenteric adipose tissues (subcutaneous, epididymal, and retroperitoneal). Mesenteric fat masses did not change after TZD treatment in OLETF rats, but nonmesenteric fat masses increased. Messenger RNA expression of lipid storage genes increased in nonmesenteric fat, but energy expenditure gene expression increased in mesenteric fat after rosiglitazone treatment. In conclusion, our findings suggest that TZD treatment may be associated with the depot-specific effects of lipid storage and energy expenditure genes on fat redistribution in individual adipose tissues in OLETF rats.

Effect of hypoxia-inducible VEGF gene expression on revascularization and graft function in mouse islet transplantation

For gene transfer strategies to improve islet engraftment, vascular endothelial growth factor (VEGF) expression should be regulated in a way that matches the transient nature of revascularization with simultaneously avoiding undesirable effects of overexpression. The aim of this study was to investigate the effects of hypoxia‐inducible VEGF gene transfer using the RTP801 promoter on islet grafts. We implanted pSV‐hVEGF transfected, pRTP801‐hVEGF transfected or nontransfected mouse islets under the kidney capsule of streptozotocin‐induced diabetic syngeneic mice. Human VEGF immunostaining of day 3 grafts revealed that the pRTP801‐hVEGF transfected group had higher hVEGF expression compared with the pSV‐hVEGF transfected group. BS‐1 staining of day 3 grafts from the pRTP801‐hVEGF transfected group showed the highest vascular density, which was comparable with day 6 grafts from the nontransfected group. In 360 islet equivalent (IEQ)‐transplantation which reverted hyperglycemia in all mice, the area under the curve of glucose levels during intraperitoneal glucose tolerance test 7u2003weeks post‐transplant was lower in mice transplanted with pRTP801‐hVEGF transfected grafts compared with mice transplanted with nontransfected grafts. In 220 IEQ‐transplantations, diabetic mice transplanted with pRTP801‐hVEGF islets became normoglycemic more rapidly compared with mice transplanted with pSV‐hVEGF or nontransfected islets, and diabetes reversal rate after 50u2003days was 90%, 68%, and 50%, respectively. In conclusion, our results indicate that regulated overexpression of hVEGF in a hypoxia‐inducible manner enhances islet vascular engraftment and preserves islet function overtime in transplants.

Apigenin induces c-Myc-mediated apoptosis in FRO anaplastic thyroid carcinoma cells.

Apigenin promotes apoptosis in cancer cells. We studied the effect of apigenin on cell survival and c-Myc expression in FRO anaplastic thyroid carcinoma (ATC) cells. Apigenin caused apoptosis via the elevation of c-Myc levels in conjunction with the phosphorylation of p38 and p53. In the c-Myc siRNA-transfected and apigenin-treated cells, compared with the apigenin-treated control cells, apoptosis and phosphorylation of p38 and p53 were ameliorated. In the presence of apigenin, diminution of p38 and p53 did not affect cell survival although apigenin activated the phosphorylation of p38 and p53 via increased c-Myc levels. In conclusion, our results indicate that apigenin induces apoptosis mediated via c-Myc with concomitant phosphorylation of p53 and p38 in FRO ATC cells. These findings suggest that augmented c-Myc acts as a core regulator and is necessary for apigenin-induced apoptosis in FRO ATC cells.