Seungjoon Oh

Sarcopenia is independently associated with cardiovascular disease in older Korean adults: the Korea National Health and Nutrition Examination Survey (KNHANES) from 2009.

Background The association between sarcopenia and cardiovascular disease (CVD) in elderly people has not been adequately assessed. The aim of this study was to investigate whether CVD is more prevalent in subjects with sarcopenia independent of other well-established cardiovascular risk factors in older Korean adults. Method This study utilized the representative Korean population data from the Korea National Health and Nutrition Examination Survey (KNHANES) which was conducted in 2009. Subjects older than 65 years of age with appendicular skeletal muscle mass (ASM) determined by dual energy X-ray absorptiometry were selected. The prevalence of sarcopenia in the older Korean adults was investigated, and it was determined whether sarcopenia is associated with CVD independent of other well-known risk factors. Results 1,578 subjects aged 65 years and older with the data for ASM were selected, and the overall prevalence of sarcopenia was 30.3% in men and 29.3% in women. Most of the risk factors for CVD such as age, waist circumference, body mass index, fasting plasma glucose and total cholesterol showed significant negative correlations with the ratio between appendicular skeletal muscle mass and body weight. Multiple logistic regression analysis demonstrated that sarcopenia was associated with CVD independent of other well-documented risk factors, renal function and medications (OR, 1.768; 95% CI, 1.075–2.909, P = 0.025). Conclusions Sarcopenia was associated with the presence of CVD independent of other cardiovascular risk factors after adjusting renal function and medications.

Sp1-Dependent Regulation of the RTP801 Promoter and Its Application to Hypoxia-Inducible VEGF Plasmid for Ischemic Disease

AbstractPurpose. Gene therapy using vascular endothelial growth factor (VEGF) is a new potential treatment of ischemic disease. To be safe and effective, VEGF expression should be enhanced locally in ischemic tissue. In this study, we identified the cis-regulatory element for the hypoxia induction of the RTP801 promoter. In addition, pRTP801-VEGF was evaluated as a therapeutic plasmid in vitro. Methods. The cis-regulatory element for hypoxia induction was identified by deletion and mutation analyses. Antisense oligonucleotide co-transfection assay was performed to evaluate the role of Sp1. pRTP801-VEGF was constructed by the insertion of the RTP801 promoter into the VEGF plasmid. The hypoxia-inducible expression of VEGF was evaluated by in vitro transfection assay. Results. In luciferase assay, the region between -495 and -446 was responsible for the hypoxia-induced transcription. The mutation of the Sp1 site in this region reduced hypoxia-induced transcription. In addition, co-transfection with antisense Sp1 oligonucleotide suggests that hypoxia induction of the RTP801 promoter is mediated by Sp1. In vitro transfection showed that pRTP801-VEGF had higher VEGF expression than pEpo-SV-VEGF. In addition, VEGF expression by pRTP801-VEGF was induced under hypoxia. Conclusions. With strong basal promoter activity and induction under hypoxia, pRTP801-VEGF may be useful for gene therapy for ischemic disease.

Decrease in carotid intima media thickness after 1 year of cilostazol treatment in patients with type 2 diabetes mellitus

A multicenter exploratory study at three university hospitals was performed to evaluate the effect of oral cilostazol on intima media thickness (IMT) in diabetic patients. A total of 141 patients was recruited in this study and randomized into a cilostazol group and a placebo (control) group. One hundred and twenty patients completed the study (i.e. 60 on cilostazol and 60 on placebo). Biochemical profiles and the IMT of the common carotid artery (CCA) determined by high-resolution B-mode ultrasonography were measured at 0, 6, and 12 months after the oral administration of 100--200 mg of cilostazol or placebo (i.e. two or four times daily for 12 months). Clinical and biochemical characteristics, the treatment modality, and microvascular diabetic complications after randomization were not significantly different between the two groups after the study. In the cilostazol treatment group, left CCA average IMT significantly decreased from 0.94+/-0.03 to 0.91+/-0.02 mm at 6 months (P<0.05), and thereafter increased to 0.92+/-0.01 mm (P>0.05) at 12 months, whereas in the control group, it increased from 0.92+/-0.03 to 0.93+/-0.01 mm at 6 months (P>0.05), and to 0.94+/-0.01 mm at 12 months (P>0.05). As for the right CCA average IMT, it decreased from 0.83+/-0.03 to 0.82+/-0.01 mm at 6 months (P<0.05), and to 0.81+/-0.01 mm at 12 months (P<0.05) in the cilostazol group, whereas it increased from 0.87+/-0.03 to 0.89+/-0.01 mm at 6 months (P<0.05), and to 0.90+/-0.01 mm at 12 months (P<0.05) in the control group (P<0.05). After correction for risk factors such as blood pressure, smoking, and lipid profiles, there were significant changes in left and right CCA average IMT for both groups (P<0.05). Left and right CCA average IMT was significantly different between the two groups (P<0.05). After making statistical corrections for blood pressure, smoking, and lipid profiles, the differences between these two groups remained significant (P<0.05). Meanwhile, there were no differences between the groups in the change of risk factors such as BMI, blood pressure, blood sugar, HbA(1c), and lipid profiles. Generally, cilostazol was well tolerated and the most common side effect in the cilostazol group was headache (12/60), mostly early in the treatment regimen. The results suggest that oral cilostazol may be helpful in the treatment of atherosclerosis in type 2 diabetic patients, although conventional cardiovascular risk factors remained unmodified.

Kaempferol protects HIT-T15 pancreatic beta cells from 2-deoxy-D-ribose-induced oxidative damage

During the progression of Type 2 diabetes, glucose toxicity is likely to contribute importantly to progressive beta cell failure. Oxidative stress is an important aspect of glucose toxicity in pancreatic beta cells, and reducing sugars, such as 2‐deoxy‐D‐ribose (dRib), produce reactive oxygen species. Furthermore, many of the biological properties of flavonoids are likely to be related to their antioxidant and free‐radical scavenging abilities. Accordingly, in the present study, we investigated whether kaempferol (a flavonol) protects beta cells from dRib‐induced oxidative damage. HIT‐T15 cells were cultured with various concentrations of dRib for 24h. Cell survivals, amounts of reactive oxygen species (ROS) generated, apoptosis, and lipid peroxidation were measured. dRib was found to dose‐dependently reduce cell survival and to markedly increase intracellular ROS levels, apoptosis, and lipid peroxidation. However, kaempferol (10 µM) suppressed dRib (20 mM) induced intracellular ROS, apoptosis, and lipid peroxidation. So, we demonstrate that kaempferol reduces dRib‐mediated beta cell damage interfering with ROS metabolism and protective effects against lipid peroxidation. Our findings indicate that kaempferol protects HIT‐T15 cells from dRib‐induced associated oxidative damage. Copyright

Autoimmune Hypoglycemia in a Patient with Characterization of Insulin Receptor Autoantibodies

Background Type B insulin resistance syndrome is a manifestation of autoantibodies to the insulin receptor that results in severe hyperglycemia and acanthosis nigricans. However, the mechanisms by which these autoantibodies induce hypoglycemia are largely unknown. In this paper, we report the case of patient with type B insulin resistance syndrome who presented with frequent severe fasting hypoglycemia and acanthosis nigricans. Methods To evaluate the mechanism of hypoglycemia, we measured the inhibition of insulin binding to erythrocytes and IM9 lymphocytes in a sample of the patients dialyzed serum before and after immunosuppressive therapy. Results In the patients pre-treatment serum IgG, the binding of 125I-insulin to erythrocytes was markedly inhibited in a dose-dependent manner until the cold insulin level reached 10-9 mol/L. We also observed dose-dependent inhibition of insulin binding to IM9 lymphocytes, which reached approximately 82% inhibition and persisted even when diluted 1:20. After treatment with glucocorticoids, insulin-erythrocyte binding activity returned to between 70% and 80% of normal, while the inhibition of insulin-lymphocyte binding was reduced by 17%. Conclusion We treated a patient with type B insulin resistance syndrome showing recurrent fasting hypoglycemia with steroids and azathioprine. We characterized the patients insulin receptor antibodies by measuring the inhibition of insulin binding.

Hemoglobin A1c May Be an Inadequate Diagnostic Tool for Diabetes Mellitus in Anemic Subjects

Background Recently, a hemoglobin A1c (HbA1c) level of 6.5% has been determined to be a criterion for diabetes mellitus (DM), and it is a widely used marker for the diagnosis of DM. However, HbA1c may be influenced by a number of factors. Anemia is one of the most prevalent diseases with an influence on HbA1c; however, its effect on HbA1c varies based on the variable pathophysiology of anemia. The aim of this study was to determine the effect of anemia on HbA1c levels. Methods Anemic subjects (n=112) and age- and sex-matched controls (n=217) who were drug naive and suspected of having DM were enrolled. The subjects underwent an oral glucose tolerance test and HbA1c simultaneously. We compared mean HbA1c and its sensitivity and specificity for diagnosing DM between each subgroup. Results Clinical characteristics were found to be similar between each subgroup. Also, when glucose levels were within the normal range, the difference in mean HbA1c was not significant (P=0.580). However, when plasma glucose levels were above the diagnostic cutoff for prediabetes and DM, the mean HbA1c of the anemic subgroup was modestly higher than in the nonanemic group. The specificity of HbA1c for diagnosis of DM was significantly lower in the anemic subgroup (P<0.05). Conclusion These results suggest that the diagnostic significance of HbA1c might be limited in anemic patients.

Evaluation of Glycemic Variability in Well-Controlled Type 2 Diabetes Mellitus

AIMS It is necessary to evaluate glucose variability and postprandial hyperglycemia in patients with well-controlled type 2 diabetes mellitus because of the limitations associated with hemoglobin A1c (HbA1c) measurements. We evaluated parameters reflecting postprandial hyperglycemia and glycemic variability in patients with optimal HbA1c. PATIENTS AND METHODS Thirty-nine patients with HbA1c levels below 7% were recruited to the study. A continuous glucose monitoring system (CGMS) was applied for two 72-h periods. 1,5-Anhydroglucitol (1,5-AG) and fructosamine (FA) were measured as parameters for postprandial hyperglycemia and glucose variability. Using CGMS data, the following postprandial hyperglycemia parameters were calculated: mean postprandial maximum glucose (MPMG) and area under the curve for glucose above 180 mg/dL (AUC-180). To measure glycemic variability, we calculated mean amplitude of glucose excursion (MAGE) using a classical (MAGEc) and new method (MAGE group of sign [MAGEgos]). RESULTS The baseline HbA1c level was 6.3±0.3%. The mean MPMG was 10.34±1.84 mmol/L, and the mean AUC-180 was 0.17±0.23 mmol/L/day. The mean MAGEgos was 3.27±1.29 mmol/L, and MAGEc was 4.30±1.43 mmol/L, indicating glycemic variability in our patients. The mean levels of 1,5-AG and FA were 16.7±7.4 μg/mL and 273.0±22.5 μmol/L, respectively. In a correlation analysis, FA was significantly correlated with MPMG, AUC-180, MAGEgos, and MAGEc. In contrast, 1,5-AG was only correlated with AUC-180. CONCLUSIONS This study demonstrated postprandial hyperglycemia and glycemic variability in subjects with well-controlled diabetes. FA may reflect postprandial hyperglycemia and glycemic variability, but 1,5-AG may be of limited value for assessing glucose variability in patients with well-controlled type 2 diabetes mellitus.

Characteristics of insulin resistance and insulin secretory capacity in Korean subjects with IFG and IGT

Both IFG and IGT are prediabetic conditions that can progress to type 2 DM. However, previous studies have shown that these are not identical. This study was conducted on 307 drug naïve prediabetic adults who did not meet the diagnostic criteria for diabetes based on the OGTT. According to the OGTT, the subjects were divided into isolated IFG (i-IFG), isolated IGT (i-IGT), and combined glucose intolerance (CGI) group. We also measured insulin resistance indices (HOMA-IR, WBISI), an insulin secretion indices (insulinogenic index [IGI], AUC I/G(0-120), disposition index [DI]), and compared each of the three groups. The OGTT measurements showed that 87 subjects were diagnosed with i-IFG, 75 subjects had i-IGT, and 145 subjects had CGI. With respect to the insulin resistance indices, HOMA-IR and WBISI were not significantly different. However, insulin secretory capacity, the IGI and DI were significantly higher for the i-IFG group. Moreover, after confounders were adjusted, HOMA-IR, IGI, AUC I/G(0-120), and the DI were significantly higher for the i-IFG group and WBISI was significantly higher for the i-IGT group. These results demonstrate that the pathogenesis of IFG is more closely associated with insulin resistance, and the pathogenesis of IGT is more closely associated with impaired insulin secretion.

Clinical experience of an iontophoresis based glucose measuring system.

Currently finger pricking is the common method of blood glucose measurement in patients with diabetes mellitus. However, diabetes patients have proven to be reluctant to check their glucose profiles regularly because of the discomfort associated with this technique. Recently, a non-invasive and continuous Reverse Iontophoresis based Glucose Monitoring Device (RIGMD) was developed in Korea. The study was conducted during the period November 2003-January 2004 on 19 in-patients. Glucose measurements were performed using RIGMD between 10 a.m. and 4 p.m. Concurrent plasma glucose levels were checked hourly and subsequently compared with RIGMD data. The mean error of RIGMD measurements was -3.45±52.99 mg/dL with a mean absolute relative error of 20±15.16%. Measurements obtained by RIGMD were correlated with plasma glucose levels (correlation coefficient; 0.784 (p<0.05)) and this correlation was independent of time of data collection. However, after excluding confounding variables this correlation coefficient exhibited a tendency to increase. 98.9% of the results were clinically acceptable by Clarke error grid analysis. We concluded that RIGMD does not have the reliability and accuracy required to wholly replace conventional methods. However, further technical advancements that reduce its shortcomings would make this device useful for the management of diabetes.

Diabcare Asia 2001 - Korea : Country Report on Outcome Data and Analysis

Background The Diabcare-Asia study was designed for the purpose of describing diabetes control and management, and late complication status in the diabetic population. Methods From the 1st of July 2001 to the 1st of September 2001, data from 1170 diabetic patients were collected in 21 centers (one university hospital and 20 clinics located in Seoul and in Gyeonggi, Korea), and blood samples were collected for centralized HbA1c measurements. Results Only 16.8% of patients at the clinics reported self-monitoring their blood glucose. The mean HbA1c was 7.3±1.4% at the hospital and 7.5±1.5% at the clinics, and the mean fasting plasma glucose (FPG) levels were 7.0±3.3 mmol/L at the hospital and 7.9±2.5 mmol/L at the clinics. About 40% of patients had a HbA1c and FPG above the normal upper limits. Screening for microalbuminuria was rarely performed. The available data represents only about 0.9% of the patients at the hospital and 12.3% of the patients at the clinics. Nephropathy (serum creatinine >2 mg/dL) was found in 0.8% of the patients at the hospital and in 3.4% of the patients at the clinics. Retinopathy and neuropathy were commonly reported diabetic complications. The prevalence of other severe late complications was relatively low. Conclusion The data revealed suboptimal glycemic control in about 40% of patients.