Hyung Joon Yoo

The relationship between serum resistin, leptin, adiponectin, ghrelin levels and bone mineral density in middle-aged men

Objective Body weight is a significant predictor of bone mass. Hormonal factors such as sex hormones, insulin, leptin and adiponectin are thought to play a role in the mechanisms controlling the association of body weight and fat mass with bone mass. However, contradictory results have been reported for the association between serum adipocytokines and bone mineral density (BMD). We therefore examined whether the serum adipocytokine and ghrelin levels, markers of fat metabolism, are associated with BMD in male adults.

Prevalence of obesity and metabolic syndrome in Korean adults.

We studied the prevalence and trend of obesity and metabolic syndrome in Korean adults aged at least 20 years using Korean National Health Examination and Nutrition Survey data from 1998 and 2001. The prevalence of body mass index (BMI) ≥ 25 kg m−2 among Korean adults in 2001 was 32.9% in men and 27.4% in women, and the number of Korean men with BMI ≥ 25 kg m−2 has increased markedly since 1998. A significant positive association between obesity and socioeconomic status was found in Korean men, whereas a significant negative association was identified in Korean women. The prevalence rates of waist circumference (WC) ≥ 90 cm in men and WC ≥ 85 cm in women were 23.4% and 23.1% in 2001 respectively. The prevalence of metabolic syndrome among Korean adults was 15–30% according to various criteria of metabolic syndrome. Future studies are needed to determine the changes in prevalence of obesity and contributing factors for obesity in Koreans.

Circulating osteoprotegerin and receptor activator of NF‐κB ligand system are associated with bone metabolism in middle‐aged males

Objective  Osteoporosis is a growing health problem in males as well as in females. Sex hormones and insulin‐like growth factor‐I (IGF‐I) have been shown to be the major determinants in male bone metabolism. Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the receptor activator of NF‐κB ligand (RANKL). OPG and RANKL have been shown to be important regulators of osteoclastogenesis. However, the relationship between the OPG‐RANKL system and male bone status in human populations are unclear. Thus, the aim of this study was to investigate the relationship between the OPG‐RANKL system and bone mineral metabolism in males.

The effect of high-dose vitamin D supplementation on insulin resistance and arterial stiffness in patients with type 2 diabetes.

Background/Aims Recent epidemiological studies revealed a striking inverse relationship between vitamin D levels, glucose intolerance/insulin resistance (IR), and cardiovascular disease. However, few interventional studies have evaluated the effect of vitamin D supplementation on cardiovascular risk, such as IR and arterial stiffness, in diabetes. We investigated the role of vitamin D supplementation on cardiovascular risk in type 2 diabetes patients, including metabolic parameters, IR, and arterial stiffness. Methods We enrolled patients who were taking antidiabetic medications or managed their diabetes using lifestyle changes. We excluded patients who were taking vitamin D or calcium supplements. We randomized participants into the vitamin D group (cholecalciferol 2,000 IU/day + calcium 200 mg/day, n = 40) or the placebo group (calcium 200 mg/day, n = 41). We compared their IR (homeostasis model of assessment [HOMA]-IR) and arterial stiffness (brachial-ankle pulse wave velocity and radial augmentation index) before and after 24 weeks of intervention. Results The baseline characteristics of the two groups were similar. A total of 62 participants (placebo, 30; vitamin D, 32) completed the study protocol. At the end of the study period, the 25-hydroxyvitamin D [25(OH)D] levels were significantly higher in the vitamin D group than in the placebo group (35.4 ± 8.5 ng/mL vs. 18.4 ± 7.3 ng/mL, p < 0.001). There was no difference in HOMA-IR or changes in arterial stiffness (placebo, 21, vitamin D, 24) between the groups. Conclusions Our data suggest that high-dose vitamin D supplementation might be effective in terms of elevating 25(OH)D levels. However, we identified no beneficial effects on cardiovascular risk in type 2 diabetes, including IR and arterial stiffness.

The Prevalence and Factors Associated with Hearing Impairment in the Korean Adults: The 2010–2012 Korea National Health and Nutrition Examination Survey (Observational Study)

AbstractThere are few studies that have used audiometric testing to gauge the demographic characteristics and associated risk factors for hearing loss at the national-level. Here, we investigated the weighted prevalence and associated factors of hearing impairment in 16,040 Korean adult population. Subjects completed audiometric test and laboratory examination as part of the data from The 2010–2012 Korea National Health and Nutrition Examination Survey (KNHANES). In our respective study, the overall weighted (n = 33,762,584) prevalence of mild hearing impairment among the Korean adult population was 20.5% (95% clearance [CI], 19.6–21.6), whereas moderate-to-profound hearing impairment was 9.2% (95% CI, 8.6–9.9). The weighted prevalence of mild hearing impairment in younger adults (19–39 years’ old) was 4.4% (3.5–5.5), in middle-age adults (40–64 years), it was 21.1% (19.8–22.5), and in older adults (≥65 years’ old), it was 69.7% (67.8–71.6). Logistic regression analyses were performed for low/mid frequency or high-frequency mild hearing impairment with age, sex, tobacco use, heavy alcohol use, educational background, occupational noise exposure, obesity, hypertension, diabetes, total serum cholesterol, and estimated glomerular filtration rate (eGFR) <60 mL/min/1.73m2 as covariates. The analyses revealed independent correlations between increased age, tobacco use, education, hypertension, and eGFR <60 mL/min/1.73m2, and low/mid frequency and high frequency mild hearing impairment. High frequency mild hearing impairment was positively correlated with male sex, diabetes, and an increase in total serum cholesterol. Taken together, hearing impairment in Korea is highly prevalent with approximately one-fifth of Korean adult reporting mild hearing impairment. This study suggests that individuals with cardiovascular risk factors such as hypertension, diabetes, smoking, increased serum cholesterol, or decreased eGFR are at particular risk of developing hearing impairment. As such, these groups may benefit from hearing loss screening in addition to those groups typically considered to be of elevated risk including geriatrics, those of low socioeconomic status, and those with considerable occupational noise exposure.

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

BACKGROUND We 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. METHODS Included 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. RESULTS The 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. CONCLUSIONS This 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 relationship between circulating osteoprotegerin levels and bone mineral metabolism in healthy women

objective  Osteoprotegerin (OPG) is a recently identified cytokine that acts as a decoy receptor for the RANK ligand. Moreover, OPG has been shown to be an important inhibitor of osteoclastogenesis in animal models. However, the relationship between circulating OPG levels and female bone status in human populations is unclear. In this study we undertook to investigate the relationship between circulating OPG levels and bone mineral metabolism in healthy women.

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.

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 7 weeks 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 50 days 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.