[show abstract][hide abstract] ABSTRACT: Although diabetes mellitus is an important risk factor of coronary artery disease (CAD), routine screening for CAD is not recommended for asymptomatic diabetic patients. We assessed the impact of chest pain on CAD risk according to the presence or absence of diabetes mellitus.
We investigated the future CAD event rate in subjects with and without chest pain according to the presence or absence of diabetes in a prospective large-scale community-based study in Korea.
Among 8,574 subjects (4,032 men and 4,542 women) without a history of CAD, 0.8% and 2.2% of non-diabetic and diabetic subjects, respectively, reported newly developed CAD events during 4 years of follow-up. Although the presence of chest pain at baseline was also significantly associated with an increased risk of CAD of more than 2-fold in both non-diabetic and diabetic subjects (P < 0.01), the risk of future CVD event in asymptomatic diabetic patients was not significantly different from that in non-diabetic subjects with chest pain (hazard ratio, 0.907; 95% confidence interval, 0.412 -- 1.998).
The CAD event rate of asymptomatic subjects with diabetes was comparable to that of non-diabetic subjects reporting chest pain. Considering the high risk of CAD in asymptomatic diabetic patients, more clinical trials aimed at formulating strategies to screen asymptomatic diabetic subjects should be carried out.
[show abstract][hide abstract] ABSTRACT: This study focused on the characterization of mesenchymal stromal cells (MSCs) from the chorion of human full term placenta from 15 donors. Chorionic MSCs revealed homologous fibroblast-like morphology and expressed CD73, CD29, CD105, and CD90. The hematopoietic stem cell markers including HLA DR, CD11b, CD34, CD79a, and CD45 were not expressed. The growth kinetics of their serial passage was steady at the later passages (passage 10). The multilineage capability of chorionic MSCs was demonstrated by successful adipogenic, osteogenic and chondrogenic differentiation and associated gene expression. Chorionic MSCs expressed genes associated with undifferentiated cells (NANOG, OCT4, REX1) and cardiogenic or neurogenic markers such as SOX2, FGF4, NES, MAP2, and NF. TERT was negative in all the samples. These findings suggest that chorionic MSCs undifferentiated stem cells and less likely to be transformed into cancer cells. A low HLA DR expression suggests that chorionic MSCs may serve as a great source of stem cells for transplantation because of their immune-privileged status and their immunosuppressive effect. Based on these unique properties, it is concluded that chorionic MSCs are pluripotent stem cells that are probably less differentiated than BM-MSCs, and they have considerable potential for use in cell-based therapies.
Journal of Korean medical science 08/2012; 27(8):857-63. · 0.84 Impact Factor
[show abstract][hide abstract] ABSTRACT: The C1q TNFα-related protein (C1QTNF) families exhibit a C-terminal complement factor C1q globular domain similar to that of TNF. However, their clinical implications are largely unknown. We recently found that the C1q TNFα-related protein isoform 5 (C1QTNF5 or myonectin) level was increased in insulin-resistant rodents and mitochondrial DNA (mtDNA)-depleted myocytes.
We aimed to determine the effects of aerobic exercise training on C1QTNF5 level and its association with insulin resistance and mtDNA density in young and old healthy women.
Fourteen healthy young women aged 22.5 ± 2.7 yr and 14 healthy older women aged 60.3 ± 5.2 yr performed aerobic exercise at 60-80% of maximal oxygen consumption (VO(2)max) over three 1-h sessions per week for 10 wk. Insulin resistance was assessed by homeostasis model assessment of insulin resistance and adiponectin concentration. Serum C1QTNF5 level was estimated by immunoblotting. The mtDNA/28S rRNA ratio was used to determine mtDNA density.
VO(2)max increased significantly after the exercise training from 33.1 ± 6.2 to 35.3 ± 5.3 ml/kg · min in younger women and from 23.2 ± 3.1 to 27.2 ± 4.8 ml/kg · min in older women (P < 0.05). The C1QTNF5 level and homeostasis model assessment of insulin resistance decreased significantly after exercise training and were correlated positively (r = 0.462; P < 0.01). There were negative correlations between the changes in C1QTNF5 level and the changes in VO(2)max, mtDNA density, and adiponectin level (r = -0.495, -0.672, and -0.569, respectively; all P < 0.01).
These findings suggest a physiological function for C1QTNF5 (myonectin) in linking insulin resistance with quantitative changes in mtDNA. Further research exploring the role of C1QTNF5 in the development of insulin resistance is warranted.
The Journal of clinical endocrinology and metabolism 01/2012; 97(1):E88-93. · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: Patients with type 2 diabetes have an increased risk of cardiovascular disease. Few studies have evaluated the cardiovascular disease (CVD) risk simultaneously using the United Kingdom Prospective Diabetes Study (UKPDS) risk engine and non-invasive vascular tests in patients with newly diagnosed type 2 diabetes.
Participants (n=380; aged 20 to 81 years) with newly diagnosed type 2 diabetes were free of clinical evidence of CVD. The 10-year coronary heart disease (CHD) and stroke risks were calculated for each patient using the UKPDS risk engine. Carotid intima media thickness (CIMT), flow mediated dilation (FMD), pulse wave velocity (PWV) and augmentation index (AI) were measured. The correlations between the UKPDS risk engine and the non-invasive vascular tests were assessed using partial correlation analysis, after adjusting for age, and multiple regression analysis.
The mean 10-year CHD and 10-year stroke risks were 14.92±11.53% and 4.03±3.95%, respectively. The 10-year CHD risk correlated with CIMT (P<0.001), FMD (P=0.017), and PWV (P=0.35) after adjusting for age. The 10-year stroke risk correlated only with the mean CIMT (P<0.001) after adjusting for age. FMD correlated with age (P<0.01) and systolic blood pressure (P=0.09). CIMT correlated with age (P<0.01), HbA1c (P=0.05), and gender (P<0.01).
The CVD risk is increased at the onset of type 2 diabetes. CIMT, FMD, and PWV along with the UKPDS risk engine should be considered to evaluate cardiovascular disease risk in patients with newly diagnosed type 2 diabetes.
[show abstract][hide abstract] ABSTRACT: We investigated the prevalence and risk factors of vertebral fractures in Korea. In a community-based prospective epidemiology study, 1,155 men and 1,529 women (mean age 59 years, range 43-74) were recruited from Ansung, a rural Korean community. Prevalent vertebral fractures were identified on the lateral spinal radiographs at T11 to L4 using vertebral morphometry. Bone mineral density (BMD) was measured at the lumbar spine, femur neck and total hip. Of the 2,684 subjects, 137 (11.9%) men and 227 (14.8%) women had vertebral fractures and the standardized prevalence for vertebral fractures using the age distribution of Korean population was 8.8% in men and 12.6% in women. In univariate analysis, older age, low hip circumference, low BMD, low income and education levels in both sexes, previous history of fracture in men, high waist-to-hip circumference ratio, postmenopausal status, longer duration since menopause, and higher number of pregnancies and deliveries in women were associated with an increased risk of vertebral fractures. However, after adjusting for age, only low BMD in both sexes and a previous history of fracture in men were significantly associated with an increased risk of vertebral fractures. Vertebral fractures are prevalent in Korea as in other countries. Older age, low BMD and a previous history of fracture are significant risk factors for vertebral fractures.
Journal of Bone and Mineral Metabolism 07/2011; 30(2):183-92. · 2.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: Food exchange lists are one of the main methods of nutritional education. However, Korean food exchange lists have not been revised since 1994. Therefore, we surveyed the opinions of diabetes educators and patients with diabetes regarding the need for revision of the current food exchange lists.
For two weeks beginning on 10 March 2008, a 12-item questionnaire regarding the opinion and need for revision of the current food exchange lists was e-mailed to diabetes educators nationwide. Another 15-question survey was administered to patients with diabetes in 13 hospitals located in the Seoul and Gyeonggi regions of Korea.
We obtained survey responses from 101 diabetes educators and 209 patients; 65 (64.3%) of the educators answered that the current food exchange lists should be revised. The items that needed revision were the glycemic index, addition of new foods and reaffirmation of exchange standard amounts. The patients demanded specific education about choosing appropriate foods, a balanced meal plan, proper snacks, and dining intake.
Our survey results demonstrate the need to revise the Korean food exchange lists. This process should focus on glycemic index, the addition of new foods and reconfirmation of one exchange reference unit.
[show abstract][hide abstract] ABSTRACT: Decreased mitochondrial function plays a pivotal role in the pathogenesis of type 2 diabetes mellitus (T2DM). Recently, it was reported that mitochondrial DNA (mtDNA) haplogroups confer genetic susceptibility to T2DM in Koreans and Japanese. Particularly, mtDNA haplogroup N9a is associated with a decreased risk of T2DM, whereas haplogroups D5 and F are associated with an increased risk. To examine functional consequences of these haplogroups without being confounded by the heterogeneous nuclear genomic backgrounds of different subjects, we constructed transmitochondrial cytoplasmic hybrid (cybrid) cells harboring each of the three haplogroups (N9a, D5, and F) in a background of a shared nuclear genome. We compared the functional consequences of the three haplogroups using cell-based assays and gene expression microarrays. Cell-based assays did not detect differences in mitochondrial functions among the haplogroups in terms of ATP generation, reactive oxygen species production, mitochondrial membrane potential, and cellular dehydrogenase activity. However, differential expression and clustering analyses of microarray data revealed that the three haplogroups exhibit a distinctive nuclear gene expression pattern that correlates with their susceptibility to T2DM. Pathway analysis of microarray data identified several differentially regulated metabolic pathways. Notably, compared to the T2DM-resistant haplogroup N9a, the T2DM-susceptible haplogroup F showed down-regulation of oxidative phosphorylation and up-regulation of glycolysis. These results suggest that variations in mtDNA can affect the expression of nuclear genes regulating mitochondrial functions or cellular energetics. Given that impaired mitochondrial function caused by T2DM-associated mtDNA haplogroups is compensated by the nuclear genome, we speculate that defective nuclear compensation, under certain circumstances, might lead to the development of T2DM.
PLoS ONE 01/2011; 6(7):e22116. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: We examined the effects of physical activity with or without dietary restriction for 3 months on regional fat and insulin sensitivity and compared the effect of total energy expenditure from all levels of physical activity with that of physical activity energy expenditure from moderate-to-vigorous exercise in obese women with Type 2 diabetes.
In this randomized, controlled trial, we assessed change of body weight, abdominal visceral fat area, subcutaneous fat area and insulin sensitivity, expressed as K(ITT), and monitored total energy expenditure and physical activity energy expenditure using an accelerometer during a 12-week intervention in four groups: control, diet, exercise and diet plus exercise.
The mean body mass index was 28.0 +/- 2.7 kg/m(2) and the mean duration of diabetes was 8 +/- 6 years. Both the diet and diet plus exercise groups showed significant body weight loss compared with the control group (P < 0.05). However, the visceral fat area was reduced only in the diet and exercise group (P = 0.017) and the subcutaneous fat area was reduced only in the diet group (P = 0.009). Mean energy intake was an independent determinant of the change in subcutaneous fat area (P = 0.020) and mean total anergy expenditure was an independent determinant of visceral fat area (P = 0.002). Insulin sensitivity K(ITT) was associated with physical activity energy expenditure (P = 0.006), energy intake (P = 0.047) and the change in fructosamine level (P = 0.016) but not with changes in body weight, subcutaneous fat area, visceral fat area or adipokine level.
Exercise had an additive effect to dietary restriction on visceral fat reduction. Visceral fat area was associated with total energy expenditure, but insulin sensitivity was associated with physical activity energy expenditure.
Diabetic Medicine 09/2010; 27(9):1088-92. · 3.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: The Reg gene has been reported to be expressed in regenerating islets and Reg1 protein to be up-regulated at an early stage of diabetes in mice. As human Reg1α is homologous with murine Reg1, we investigated whether common variants in Reg1α are associated with type 2 diabetes in the Korean population.
We sequenced the Reg1α gene to identify common polymorphisms using 24 Korean DNA samples. Of 11 polymorphisms found, five common ones (g.-385T>C [rs10165462], g.-36T>G [rs25689789], g.209G>T [rs2070707], g.1385C>G [novel], and g.2199G>A [novel]) were genotyped in 752 type 2 diabetic patients and 642 non-diabetic subjects.
No polymorphism was associated with the risk of type 2 diabetes. However, g.-385C and g.2199A lowered the risk of early-onset type 2 diabetes, defined as a diagnosis in subjects whose age at diagnosis was 25 years or more but less than 40 years (odds ratio [OR], 0.721 [0.535 to 0.971] and 0.731 [0.546 to 0.977] for g.-385C and g.2199A, respectively) and g.1385G increased the risk of early-onset diabetes (OR, 1.398 [1.055 to 1.854]). Although adjusting for errors in multiple hypotheses-testing showed no statistically significant association between the three individual polymorphisms and early-onset diabetes, the haplotype H1, composed of g.-385C, g.1385C, and g.2199A, was associated with a reduced risk of early-onset diabetes (OR, 0.590 [0.396 to 0.877], P = 0.009).
Polymorphisms in the Reg1α were not found to be associated with overall susceptibility to type 2 diabetes, though some showed modest associations with early-onset type 2 diabetes in the Korean population.
[show abstract][hide abstract] ABSTRACT: Lipid accumulation in muscle is associated with diminished insulin sensitivity. It was hypothesized that resistance exercise decreases muscular adipose tissue and reduces the level of retinol-binding protein-4 (RBP4), which is linked to adipose tissue and insulin sensitivity in diabetics. Forty-four women with type 2 diabetes were randomly assigned to three groups for a period of 12 weeks: control (asked to maintain a sedentary lifestyle); resistance exercise (elastic band exercise at moderate intensity five times per week); and aerobic exercise (walking for 60 min at moderate intensity five times per week). Subcutaneous (SCAT), subfascial (SFAT) and intramuscular (IMAT) adipose tissues at mid-thigh level were assessed using computed tomography, and RBP4 level and insulin sensitivity (fractional disappearance rate of insulin, k(ITT)) were assessed before and after intervention. Changes in SCAT, SFAT, IMAT, RBP4 and k(ITT) were similar among the three groups. Within-group analysis revealed that body mass index and waist circumference decreased significantly in both exercise groups, but RBP4 decreased significantly only with resistance exercise. Resistance exercise did not alter muscular adipose tissue or improve insulin sensitivity.
The Journal of international medical research 06/2010; 38(3):782-91. · 0.96 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aerobic exercise can effectively reduce visceral fat. However, few studies have examined the effect of daily physical activity on obesity and cardiopulmonary function in the subjects with diabetes. We examined the effect of moderate intensity of walking in obese diabetes patients by monitoring of daily activity and measuring the change in abdominal fat area, muscle are and maximal muscle strength.
We randomly assigned 27 obese women with type 2 diabetes to an aerobic exercise group (AG, n = 13) and control group (CG, n = 14). The AG performed moderate intensity walking for 60 minutes per exercise, 5 times per week, and for 12 weeks. The activity energy expenditure was monitored by a multi-record accelerometer. The CG maintained routine daily activities. At the time of the initiation of the study and after 12 weeks of exercise, the aerobic exercise capacity was assessed using oxygen consumption rate at anaerobic threshold (VO(2)-AT). The abdominal fat area and the quadriceps muscle area were measured by computed tomography, and the maximum muscle strength of the upper and lower limbs was measured by a chest press and a leg press, respectively.
The mean age of the study subjects was 56.6 +/- 8.0 years, the mean duration of diabetes was 6.3 +/- 6.0 years, and the body weight index (BMI) was 27.3 +/- 2.7 kg/m(2). The BMI of the AG was significantly decreased (P = 0.003). In the AG, the visceral fat area and subcutaneous fat area were also significantly decreased (P = 0.018 and P < 0.001, respectively) but not in CG. VO(2)-AT of the AG was significantly improved, while that of the CG did not change (P = 0.009 and P = 0.115, respectively). The quadriceps muscle mass and the maximal muscle strength of the AG did not change, however, the CG showed a significant decrease. Duration of moderate intensity exercise was correlated with the decrease in total abdominal fat area (r = -0.484; P = 0.011) and that of high intensity exercise was correlated with improvement of cardiopulmonary function (r = 0.414; P = 0.032).
Daily moderate intensity aerobic exercise is effective at reducing abdominal fat mass, while high intensity exercise improves cardiopulmonary function.
[show abstract][hide abstract] ABSTRACT: Pallister-Killian syndrome (PKS) is a rare disorder characterized cytogenetically by tetrasomy 12p for isochromosome of the short arm of chromosome 12. PKS is diagnosed by prenatal genetic analysis through chorionic villous sampling, genetic amniocentesis, and cordocentesis, or by chromosomal analysis of skin fibroblasts, but is not usually detected by chromosomal analysis of peripheral blood cells. Herein, we report a case of a gravida at 23 weeks gestation with pulmonary stenosis and right ventricular dilation of the heart which were detected by sonography. Fluorescence in situ hybridization and a multicolor banding technique were performed to verify the diagnosis as 47,XX, +mar.ish i(12)(p10)(TEL++)/46,XX, and an autopsy confirmed the cardiac anomalies detected on antenatal sonography.
The Korean Journal of Laboratory Medicine 09/2009; 29(4):366-70. · 0.72 Impact Factor
[show abstract][hide abstract] ABSTRACT: There is growing evidence for the association between bone mineral density (BMD) and vascular calcification, which is related to cardiovascular disease. Coronary multidetector row computed tomography (MDCT) is a noninvasive tool developed to evaluate coronary status precisely. We used MDCT to evaluate this association.
Eight hundred and fifteen subjects received routine checkups. After excluding subjects with factors affecting bone metabolism and cardiovascular disease, 467 subjects were analysed.
Coronary calcification was measured with MDCT and BMD was measured with dual X-ray absorptiometry (DXA).
The BMD of the femur and the lumbar spine (L-spine) were negatively associated with the coronary calcium score (CCS) after adjusting for age in women but not in men. This inverse correlation was stronger in women with a longer time since menopause (r = -0.35 at femur, postmenopausal women vs. r = -0.10 at femur, premenopausal women, P < 0.05), and it was stronger at the femur than in the L-spine (r = -0.35 at femur vs. r = -0.16 at L-spine, P < 0.01). The relationship was also stronger in postmenopausal women with osteoporosis and osteopaenia than in women with normal BMD. The lower BMD was associated with higher coronary plaque burdens and multidiseased coronary vessels in both men and women (P < 0.01).
Increased CCS and subclinical atherosclerosis of plaque burdens as revealed by MDCT was associated with a low BMD in all women, independent of cardiovascular risk factors and age.
[show abstract][hide abstract] ABSTRACT: Glucocorticoids play an important role in the pathogenesis of obesity and insulin resistance. 11beta-hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive cortisone to active cortisol, has become an emerging therapeutic target for type 2 diabetes mellitus and obesity. In this study, we examined the association between HSD11B1 polymorphisms and type 2 diabetes and metabolic phenotypes in Koreans.
We sequenced all exons including exon-intron boundaries and the promoter region of the HSD11B1 gene. Of 8 polymorphisms identified, we selected 4 common single-nucleotide polymorphisms (g.-19835G>A, g.-19609A>G, g.+27447G>C and g.+27810C>T) based on location, linkage disequilibrium and frequency and which were genotyped in 757 subjects with type 2 diabetes and 644 nondiabetic subjects.
There was no association between the 4 common polymorphisms of HSD11B1 and type 2 diabetes. g.-19835G>A and g.-19609A>G showed modest associations with fasting plasma glucose and body mass index but the significance of these associations was lost after adjustment for multiple comparison. With regard to promoter polymorphisms in the HSD11B1 gene, a haplotype construct carrying both g.-19835A and g.-19609G showed significantly decreased promoter activity compared to other common haplotype constructs.
The variations in HSD11B1 were not associated with susceptibility to type 2 diabetes or metabolic phenotypes in Koreans. However, the common promoter variants of the gene might exert a polymorphic regulatory effect on HSD11B1 expression.
Hormone Research 02/2009; 72(1):25-32. · 2.48 Impact Factor