Moonsuk Nam

Association between polymorphisms in SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1, KCNQ1 and type 2 diabetes in the Korean population

AbstractAccording to recent genome-wide association studies, a number of single nucleotide polymorphisms (SNPs) are reported to be associated with type 2 diabetes mellitus (T2DM). The aim of the present study was to investigate the association among the polymorphisms of SLC30A8, HHEX, CDKN2A/B, IGF2BP2, FTO, WFS1, CDKAL1 and KCNQ1 and the risk of T2DM in the Korean population. This study was based on a multicenter case-control study, including 908 patients with T2DM and 502 non-diabetic controls. We genotyped rs13266634, rs1111875, rs10811661, rs4402960, rs8050136, rs734312, rs7754840 and rs2237892 and measured the body weight, body mass index and fasting plasma glucose in all patients and controls. The strongest association was found in a variant of CDKAL1 [rs7754840, odds ratio (OR) = 1.77, 95% CI = 1.50–2.10, p = 5.0 × 10−11]. The G allele of rs1111875 (OR = 1.43, 95% CI = 1.18–1.72, p = 1.8 × 10−4) in HHEX), the T allele of rs10811661 (OR = 1.47, 95% CI = 1.23–1.75, p = 2.1 × 10−5) in CDKN2A/B) and the C allele of rs2237892 (OR = 1.31, 95% CI = 1.10–1.56, p = 0.003) in KCNQ1 showed significant associations with T2DM. Rs13266634 (OR = 1.19, 95% CI = 1.00–1.42, p = 0.045) in SLC30A8 showed a nominal association with the risk of T2DM, whereas SNPs in IGF2BP2, FTO and WFS1 were not associated. In conclusion, we have shown that SNPs in HHEX, CDKN2A/B, CDKAL1, KCNQ1 and SLC30A8 confer a risk of T2DM in the Korean population.

Effects of rosiglitazone and metformin on inflammatory markers and adipokines: decrease in interleukin‐18 is an independent factor for the improvement of homeostasis model assessment‐beta in type 2 diabetes mellitus

Objective  We examined the individual pharmacological effects of the addition of rosiglitazone and metformin to glimepiride on inflammatory markers and adipokines in patients with type 2 diabetes mellitus. We analysed the relationships between these variables, the measurements of insulin sensitivity and β‐cell function in patients treated with rosiglitazone plus glimepiride.

Functional and Morphologic Characterizations of the Diabetic Mouse Corpus Cavernosum: Comparison of a Multiple Low‐Dose and a Single High‐Dose Streptozotocin Protocols

INTRODUCTION With the advent of genetically modified mice, it seems particularly advantageous to develop a mouse model of diabetic erectile dysfunction. AIM To establish a mouse model of type I diabetes by implementation of either multiple low-dose streptozotocin (STZ) protocol or single high-dose STZ protocol and to evaluate morphologic alterations in the cavernous tissue and subsequent derangements in penile hemodynamics in vivo. METHODS Eight-week-old C57BL/6J mice were divided into three groups: a control group, a group administered the multiple low-dose STZ protocol (50 mg/kg x 5 days), and a group administered the single high-dose STZ protocol (200 mg/kg). MAIN OUTCOME MEASURES After 8 weeks, erectile function was measured by electrical stimulation of the cavernous nerve. The penis was then harvested and stained with hydroethidine (in situ analysis of superoxide anion), TUNEL, or antibodies to nitrotyrosine (marker of peroxynitrite formation), PECAM-1, smooth muscle alpha-actin, and phospho-eNOS. Penis specimens from a separate group of animals were used for phospho-eNOS and eNOS western blot or cGMP determination. RESULTS Erectile function was significantly less in diabetic groups than in control group. The generation of superoxide anion and nitrotyrosine and the number of apoptotic cells in both cavernous endothelial and smooth muscle cells were significantly higher in diabetic groups than in control group. Cavernous tissue phospho-eNOS and cGMP expression and the number of endothelial and smooth muscle cells were lower in diabetic groups than in control group. Both diabetic models resulted in similar structural and functional derangements in the corpus cavernosum; however, the mortality rate was higher in mice receiving single high-dose of STZ than in those receiving multiple low-doses. CONCLUSION The mouse model of type I diabetes is useful and technically feasible for the study of the pathophysiologic mechanisms involved in diabetic erectile dysfunction.

Effect of lifestyle modification on serum chemerin concentration and its association with insulin sensitivity in overweight and obese adults with type 2 diabetes

Chemerin, a recently identified adipokine, has been linked to adiposity, insulin resistance, metabolic syndrome risk factors and inflammation. Here, we evaluated whether a 12‐week lifestyle intervention in overweight and obese adults with type 2 diabetes could significantly affect the average blood glucose and serum chemerin levels over time.

Direct Medical Costs for Patients with Type 2 Diabetes and Related Complications: A Prospective Cohort Study Based on the Korean National Diabetes Program

We analyzed the direct medical costs for Korean patients with type 2 diabetes according to the type of complications and the number of microvascular complications. We analyzed costs for type 2 diabetes and associated complications in 3,125 patients. These data were obtained from the Korean National Diabetes Program (KNDP), a large, ongoing, prospective cohort study that began in 2005. The cost data were prospectively collected, using an electronic database, for the KNDP cohort at six hospitals. The costs were analyzed according to complications for 1 yr from enrollment in the study. Among 3,125 patients, 918 patients had no vascular complications; 1,883 had microvascular complications only; 51 had macrovascular complications only; and 273 had both complications. The annual direct medical costs for a patient with only macrovascular, only microvascular, or both macrovascular and microvascular complications were 2.7, 1.5, and 2.0 times higher than the medical costs of patients without complications. Annual direct medical costs per patient increased with the number of microvascular complications in patients without macrovascular complications. The economic costs for type 2 diabetes are attributable largely to the management of microvascular and macrovascular complications. Proper management of diabetes and prevention of related complications are important for reducing medical costs.

A novel 111/121 diplotype in the Calpain-10 gene is associated with type 2 diabetes

AbstractGenetic variations in the Calpain-10 gene, CAPN10, have been reported to be associated with the risk of type 2 diabetes mellitus (T2DM) in Mexican-Americans and Northern Europeans whereas these variations are not associated with T2DM in other populations. The aim of this study was to determine whether there is an association between specific CAPN10 diplotype (SNP-43, -19, and -63) and T2DM in the Korean population. Overall, 454 Korean patients with T2DM (male 230, female 224) and 236 non-diabetic controls (male 124, female 112) with no family history of diabetes were enrolled in this study. All the subjects were genotyped according to CAPN10 SNP-43, -19, and -63. The restriction fragment length polymorphism method was used for the three SNPs. There were eight estimated haplotype allelic variations. After adjusting for gender and age, the 111 haplotype was associated with a high risk of T2DM (P <0.0001). The 111/121 diplotype was associated with a high risk of T2DM (odds ratio =2.580, 95% confidence interval =1.602-4.155, P =0.001). The high-risk haplotype (112/121) in Mexican-Americans was not significant in our study population. In conclusion, we found that a novel 111/121 diplotype in Calpain-10 gene is associated with T2DM in the Korean population.

Psychometric properties of a Korean version of the summary of diabetes self-care activities measure

BACKGROUND The summary of diabetes self-care activities (SDSCA) questionnaire is one of the most widely used self-report instruments for measuring diabetes self-management in adults. OBJECTIVES This study aimed to examine the psychometric properties of a Korean version of the SDSCA questionnaire. METHODS The 11-item English version of the SDSCA was translated into Korean following the standard translation methodology. The questionnaire was administered to 208 patients with type 2 diabetes. Exploratory and confirmatory factor analyses (EFA and CFA) were carried out for construct validity. Content validity index (CVI), internal consistency and a diabetes management self-efficacy scale (DMSES) were assessed. RESULTS The CVI of a Korean version of the SDSCA was .83. The EFA yielded a 9-item measure with a four factor solution with the same labels for original scales. The results of CFA showed the goodness of fit in the 9-item Korean SDSCA version (SDSCA-K). The internal consistency of SDSCA-K was moderate (Cronbachs α=.69) and the positive correlation between the SDSCA-K and the DMSES was identified. CONCLUSION The current study provides the initial psychometric properties of SDSCA-K modified to 9 items and supports SDSCA-K as a reliable and valid measure of diabetes self-management in Korean patients.

Development and Validation of a Semi-Quantitative Food Frequency Questionnaire to Assess Diets of Korean Type 2 Diabetic Patients

Background Our aim was to assess the validity of a semi-quantitative food frequency questionnaire (FFQ) by comparison with the 3-day diet record (DR) in patients with type 2 diabetes. Methods Eighty five type 2 diabetic patients (aged 33 to 70 years) from the Korean National Diabetes Program (KNDP) completed 3-day DR and FFQ. The FFQ was designed to reflect the eating pattern of Korean type 2 diabetic patients, and was based on the 2003 Korean National Health and Nutrition Examination Survey. The FFQ consists of 85 food items and 12 food groups. The validity of FFQ was assessed by comparison with the 3-day DR. Results The mean age was 49 ± 10 years. Clinical characteristic including body weight, diabetic duration, and HbA1c were not different from the total cohort subjects (n = 1,478). There were no significant differences in the mean intake of protein, fat and calcium estimated by the FFQ and the 3-day DR. Energy and carbohydrate estimated by the FFQ were higher than those estimated by the 3-day DR. The correlation coefficient was highest for energy (r = 0.740; P < 0.00) and lowest for iron (r = 0.269; P < 0.05). The Kappa values for energy, carbohydrate, protein, fat and calcium were 0.54, 0.37, 0.36, 0.46, and 0.19, respectively. Conclusion The FFQ is a reasonable instrument for assessing the intake of most macronutrients in Korean type 2 diabetes, although careful consideration is required for the food groups and nutrients for which the FFQ had low validity.

The C609T variant of NQO1 is associated with carotid artery plaques in patients with type 2 diabetes.

OBJECTIVE Atherosclerosis in patients with type 2 diabetes has been linked to oxidative stress. NADP[1]:quinone oxidoreductase 1 (NQO1) plays a key role in cellular antioxidant defense. Recent reports suggest that highly expressed and inducible endogenous NQO1 from cardiovascular cells may act as a potential superoxide scavenger. We examined the relationship between the risk of NQO1 C609T polymorphism and carotid artery atherosclerosis in patients with type 2 diabetes. METHODS We recruited 601 (Seoul set) and 233 (Koyang set) unrelated patients with type 2 diabetes from independent groups. The C609T variant of NQO1 was genotyped by Taqman RT-PCR. Mean and maximum carotid intima-media thickness (IMT) and carotid artery plaques were measured by high-resolution ultrasonography. RESULTS Patients with the T allele exhibited a higher prevalence of atherosclerotic plaques than non-T allele carriers in both sets (Seoul set vs. Koyang set, p=0.021, p=0.023, respectively). After adjusting for age, sex, duration of diabetes, systolic blood pressure, body mass index, current smoking, HDL-cholesterol, LDL-cholesterol and HbA1c, subjects with the T allele had a significantly higher risk of carotid artery plaques (Seoul set vs. Koyang set, OR=1.65, p=0.015; OR=2.00, p=0.037, respectively) than subjects with the CC genotype. CONCLUSION These results suggest that the C609T polymorphism of NQO1 is associated with carotid artery plaques in type 2 diabetic patients.

VIBRATION CONTROL EVALUATION OF A COMMERCIAL VEHICLE FEATURING MR SEAT DAMPER

This paper presents vibration control responses of a commercial vehicle installed with electro-rheological (ER) primary suspensions and a magneto-rheological (MR) seat damper. After formulating the governing equation of motion of the full-vehicle system associated ER and MR dampers, the sky-hook controllers are designed by imposing semi-active actuating conditions. The control algorithms are then implemented via the hardware-in-the-loop simulation, and control responses of vertical displacement and acceleration at the driver’s seat are evaluated under two road conditions; bump and random road.