[show abstract][hide abstract] ABSTRACT: Aging is associated with chronic low-grade inflammation, and interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are key mediators of the inflammatory process. IL-6, especially muscle-derived IL-6, is expected to mediate the beneficial metabolic effects of exercise. There was no report that directly compares the effects of chronic endurance exercise on cytokine responses between old and young subjects in the same situation. Therefore, we compared the effects of endurance exercise on the expression of IL-6 and TNF-α in old and young rats. Young (3-month-old) and old (20-month-old) male Fisher rats were trained for 12 weeks on the treadmill. We measured serum TNF-α and IL-6 concentrations by enzyme-linked immunosorbent assay and examined mRNA expression of TNF-α and IL-6 in muscle, liver, and white adipose tissue using reverse transcription - polymerase chain reaction. We found that old rats had higher basal IL-6 levels in the liver, as well as in the serum and the muscle. After chronic endurance exercise, young rats exhibited significant decreases in serum TNF-α levels and hepatic IL-6 expression. However, old rats exhibited no significant changes in either serum or tissue cytokine levels after endurance exercise. These findings suggest that chronic endurance exercise could influence the inflammatory response of hepatic tissues, as well as muscle, and that the effects of chronic endurance exercise on inflammatory cytokine levels are different between old and young rats and an exercise program tailored for old subjects will be needed to obtain beneficial anti-inflammatory effects from exercise.
[show abstract][hide abstract] ABSTRACT: The N-end rule pathway is a proteolytic system in which N-terminal residues of short-lived proteins are recognized by recognition components (N-recognins) as essential components of degrons, called N-degrons. Known N-recognins in eukaryotes mediate protein ubiquitylation and selective proteolysis by the 26S proteasome. Substrates of N-recognins can be generated when normally embedded destabilizing residues are exposed at the N terminus by proteolytic cleavage. N-degrons can also be generated through modifications of posttranslationally exposed pro-N-degrons of otherwise stable proteins; such modifications include oxidation, arginylation, leucylation, phenylalanylation, and acetylation. Although there are variations in components, degrons, and hierarchical structures, the proteolytic systems based on generation and recognition of N-degrons have been observed in all eukaryotes and prokaryotes examined thus far. The N-end rule pathway regulates homeostasis of various physiological processes, in part, through interaction with small molecules. Here, we review the biochemical mechanisms, structures, physiological functions, and small-molecule-mediated regulation of the N-end rule pathway.
Annual review of biochemistry 04/2012; 81:261-89. · 29.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: Latent autoimmune diabetes in adults (LADA) refers to a specific type of diabetes characterized by adult onset, presence of islet auto-antibodies, insulin independence at the time of diagnosis, and rapid decline in β-cell function. The prevalence of LADA among patients with type 2 diabetes varies from 2% to 20% according to the study population. Since most studies on the prevalence of LADA performed in Korea were conducted in patients who had been tested for anti-glutamic acid decarboxylase antibody (GADAb), a selection bias could not be excluded. In this study, we examined the prevalence and clinical characteristics of LADA among adult patients recently diagnosed with type 2 diabetes.
We included 462 patients who were diagnosed with type 2 diabetes within 5 years from the time this study was performed. We measured GADAb, fasting insulin level, fasting C-peptide level, fasting plasma glucose level, HbA1c, and serum lipid profiles and collected data on clinical characteristics.
The prevalence of LADA was 4.3% (20/462) among adult patients with newly diagnosed type 2 diabetes. Compared with the GADAb-negative patients, the GADAb-positive patients had lower fasting C-peptide levels (1.2±0.8 ng/mL vs. 2.0±1.2 ng/mL, P=0.004). Other metabolic features were not significantly different between the two groups.
The prevalence of LADA is 4.3% among Korean adult patients with recently diagnosed type 2 diabetes. The Korean LADA patients exhibited decreased insulin secretory capacity as reflected by lower C-peptide levels.
[show abstract][hide abstract] ABSTRACT: A role of Rho-associated coiled-coil-containing protein kinase (ROCK)1 in regulating whole-body glucose homeostasis has been reported. However, cell-autonomous effects of ROCK1 on insulin-dependent glucose transport in adipocytes and muscle cells have not been elucidated. To determine the specific role of ROCK1 in glucose transport directly, ROCK1 expression in 3T3-L1 adipocytes and L6 myoblasts was biologically modulated. Here, we show that small interfering RNA-mediated ROCK1 depletion decreased insulin-induced glucose transport in adipocytes and myoblasts, whereas adenovirus-mediated ROCK1 expression increased this in a dose-dependent manner, indicating that ROCK1 is permissive for glucose transport. Inhibition of ROCK1 also impaired glucose transporter 4 translocation in 3T3-L1 adipocytes. Importantly, the ED₅₀ of insulin for adipocyte glucose transport was reduced when ROCK1 was expressed, leading to hypersensitivity to insulin. These effects are dependent on actin cytoskeleton remodeling, because inhibitors of actin polymerization significantly decreased ROCK1's effect to promote insulin-stimulated glucose transport. Unlike ROCK2, ROCK1 binding to insulin receptor substrate (IRS)-1 was not detected by immunoprecipitation, although cell fractionation demonstrated both ROCK isoforms localize with IRS-1 in low-density microsomes. Moreover, insulin's ability to increase IRS-1 tyrosine 612 and serine 632/635 phosphorylation was attenuated by ROCK1 suppression. Replacing IRS-1 serine 632/635 with alanine reduced insulin-stimulated phosphatidylinositol 3-kinase activation and glucose transport in 3T3-L1 adipocytes, indicating that phosphorylation of these serine residues of IRS-1, which are substrates of the ROCK2 isoform in vitro, are crucial for maximal stimulation of glucose transport by insulin. Our studies identify ROCK1 as an important positive regulator of insulin action on glucose transport in adipocytes and muscle cells.
[show abstract][hide abstract] ABSTRACT: Free fatty acid-induced pancreatic β-cell dysfunction plays a key role in the pathogenesis of type 2 diabetes. We conducted gene expression microarray analysis to comprehensively investigate the transcription machinery of palmitate-regulated genes in pancreatic β-cells in vitro. In particular, mouse pancreatic βTC3 cells were treated with palmitate in the presence or absence of cycloheximide (CHX), which blocks protein synthesis and thereby allows us to distinguish immediate early genes (IEGs) from their target genes. The microarray experiments identified 34 palmitate-regulated IEGs and 74 palmitate-regulated target genes. In silico promoter analysis revealed that transcription factor binding sites for NF-κB were over-represented, regulating approximately one-third of the palmitate-regulated target genes. In cells treated with CHX, nfkb1 showed an up-regulation by palmitate, suggesting that NF-κB could be an IEG. Functional enrichment analysis of 27 palmitate-regulated genes with NF-κB binding sites showed an over-representation of genes involved in immune response, inflammatory response, defense response, taxis, regulation of cell proliferation, and regulation of cell death pathways. Electrophoretic mobility shift assay showed that palmitate stimulates NF-κB activity both in the presence and absence of CHX. In conclusion, by identifying IEGs and target genes, the present study depicted a comprehensive view of transcription machinery underlying palmitate-induced inflammation and cell proliferation/death in pancreatic β-cells and our data demonstrated the central role of NF-κB.
[show abstract][hide abstract] ABSTRACT: Knowledge regarding the genetic risk loci for gestational diabetes mellitus (GDM) is still limited. In this study, we performed a two-stage genome-wide association analysis in Korean women. In the stage 1 genome scan, 468 women with GDM and 1,242 nondiabetic control women were compared using 2.19 million genotyped or imputed markers. We selected 11 loci for further genotyping in stage 2 samples of 931 case and 783 control subjects. The joint effect of stage 1 plus stage 2 studies was analyzed by meta-analysis. We also investigated the effect of known type 2 diabetes variants in GDM. Two loci known to be associated with type 2 diabetes had a genome-wide significant association with GDM in the joint analysis. rs7754840, a variant in CDKAL1, had the strongest association with GDM (odds ratio 1.518; P=6.65×10(-16)). A variant near MTNR1B, rs10830962, was also significantly associated with the risk of GDM (1.454; P=2.49×10(-13)). We found that there is an excess of association between known type 2 diabetes variants and GDM above what is expected under the null hypothesis. In conclusion, we have confirmed that genetic variants in CDKAL1 and near MTNR1B are strongly associated with GDM in Korean women. There seems to be a shared genetic basis between GDM and type 2 diabetes.
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Treatment with trimetazidine (TMZ), 1-[2,3,4-trimethoxybenzyl] piperazine, dihydrochloride, improves cardiac function and ameliorates endothelial dysfunction. However, its potential efficacy against restenosis after balloon injury has not been addressed. We investigated the effect of TMZ on reducing the occurrence of restenosis in the carotid artery in response to balloon injury and explored potential mechanisms for the effects. MATERIAL AND METHODS: Streptozotocin (40mg/kg)-injected Sprague-Dawley rats and Otsuka Long-Evans Tokushima Fatty rats were used for type 1 and type 2 diabetes models, respectively. Both types of rats were divided into three groups: control and TMZ treatment 10 and 20mg/kg per day (n=10 per group). TMZ or normal saline was given orally from 2weeks before to 2weeks after carotid injury. RESULTS: Four weeks of TMZ treatment resulted in a significant and dose-dependent reduction in the intima-media ratio in diabetic rats. This effect was accompanied by decreased proliferation of vascular smooth muscle cells (VSMCs) and accelerated re-endothelialization after carotid balloon injury. In vitro study with VSMCs decreased proliferation and migration, while human umbilical vein endothelial cells (HUVECs) increased proliferation and decreased apoptosis after TMZ treatment. Antioxidative effects of TMZ were observed in both VSMCs and HUVECs. CONCLUSIONS: Reduction of restenosis by TMZ treatment involved changes in antioxidative and anti-inflammatory properties, which are cell-specific effects on either survival or apoptosis. The specific actions and physiological effects of TMZ may contribute to better understanding of the pathogenesis of atherosclerosis, which is a major complication of diabetes mellitus.
International journal of cardiology 01/2012; · 7.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent studies suggest an association between vitamin D activity and cardiometabolic risk.
We investigated vitamin D status and its association with subclinical atherosclerosis in a population-based cohort study, the Korean Longitudinal Study on Health and Aging (KLoSHA).
Participants were 439 men and 561 women aged 65 yr or older who were recruited by random stratified sampling for KLoSHA.
Anthropometric and biochemical parameters, the concentration of 25-hydroxyvitamin D (25-OHD), and intact PTH were measured.
We evaluated the coronary artery calcium score and stenosis using multidetector-row cardiac computed tomography, the intima-media thickness using carotid sonography, pulse wave velocity, and the ankle-brachial index.
Among the participants, 49.8, 44.2, and 6.0% had 25-OHD deficiency (<15 ng/ml), insufficiency (15-29.9 ng/ml), and adequacy (≥30 ng/ml), respectively. The frequency of coronary artery stenosis (>50%) differed between 25-OHD categories: 18.5, 12.9, and 1.9% in the 25-OHD-deficient, -insufficient, and -adequate groups, respectively (P < 0.05). After adjusting for cardiometabolic risks and intact PTH concentration, multivariate regression analysis showed that participants with a low 25-OHD concentration had a higher risk of significant coronary artery stenosis; the odds ratios were 2.08 for 25-OHD concentration of 15-29.9 ng/ml vs. at least 30 ng/ml and 3.12 for 25-OHD concentration below 15 ng/ml vs. at least 30 ng/ml (both P < 0.05).
The association between 25-OHD inadequacy and subclinical atherosclerosis underscores the clinical implications of vitamin D status. An intervention strategy to increase vitamin D level through vitamin D-fortified diet and adequate sun exposure may mitigate the consequences of vitamin D deficiency.
The Journal of clinical endocrinology and metabolism 01/2012; 97(1):169-78. · 6.50 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether the reported intercellular mitochondrial transfer could be replicated in different types of cells or under different experimental conditions, and tried to elucidate possible mechanism. Using biochemical selection methods, we found exponentially growing cells in restrictive media (uridine(-) and bromodeoxyuridine [BrdU](+)) during the coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mitochondrial DNA (mtDNA) identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B ρ(0) cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. Cytochalasin B, an inhibitor of chemotaxis and cytoskeletal assembly, blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential cell therapy-based mitochondrial restoration or mitochondrial gene therapy for human diseases caused by mitochondrial dysfunction.
PLoS ONE 01/2012; 7(3):e32778. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recently, it has been suggested that enhancement of incretin effect improves cardiac function. We investigated the effect of a DPP-IV inhibitor, des-fluoro-sitagliptin, in reducing occurrence of restenosis in carotid artery in response to balloon injury and the related mechanisms.
Otsuka Long-Evans Tokushima Fatty rats were grouped into four: control (normal saline) and sitagliptin 100, 250 and 500 mg/kg per day (n = 10 per group). Sitagliptin or normal saline were given orally from 1 week before to 2 weeks after carotid injury. After 3 weeks of treatment, sitagliptin treatment caused a significant and dose-dependent reduction in intima-media ratio (IMR) in obese diabetic rats. This effect was accompanied by improved glucose homeostasis, decreased circulating levels of high-sensitivity C-reactive protein (hsCRP) and increased adiponectin level. Moreover, decreased IMR was correlated significantly with reduced hsCRP, tumor necrosis factor-α and monocyte chemoattractant protein-1 levels and plasminogen activator inhibitor-1 activity. In vitro evidence with vascular smooth muscle cells (VSMCs) demonstrated that proliferation and migration were decreased significantly after sitagliptin treatment. In addition, sitagliptin increased caspase-3 activity and decreased monocyte adhesion and NFκB activation in VSMCs.
Sitagliptin has protective properties against restenosis after carotid injury and therapeutic implications for treating macrovascular complications of diabetes.
PLoS ONE 01/2012; 7(4):e35007. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Diabetic nephropathy (DN) is a long-term complication of diabetes mellitus that leads to end-stage renal disease. Microalbuminuria is used for the early detection of diabetic renal damage, but such levels do not reflect the state of incipient DN precisely in type 2 diabetic patients because microalbuminuria develops in other diseases, necessitating more accurate biomarkers that detect incipient DN. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify urinary proteins that were differentially excreted in normoalbuminuric and microalbuminuric patients with type 2 diabetes where 710 and 196 proteins were identified and quantified, respectively. Some candidates were confirmed by 2-DE analysis, or validated by Western blot and multiple reaction monitoring (MRM). Specifically, some differentially expressed proteins were verified by MRM in urine from normoalbuminuric and microalbuminuric patients with type 2 diabetes, wherein alpha-1-antitrypsin, alpha-1-acid glycoprotein 1, and prostate stem cell antigen had excellent AUC values (0.849, 0.873, and 0.825, resp.). Moreover, we performed a multiplex assay using these biomarker candidates, resulting in a merged AUC value of 0.921. Although the differentially expressed proteins in this iTRAQ study require further validation in larger and categorized sample groups, they constitute baseline data on preliminary biomarker candidates that can be used to discover novel biomarkers for incipient DN.
Experimental Diabetes Research 01/2012; 2012:168602. · 1.89 Impact Factor
[show abstract][hide abstract] ABSTRACT: Chemosignals from human body fluids may modulate biological functions in humans. The objective of this study was to examine whether chemosignals from human sad tears and postprandial plasma modulate appetite. We obtained fasting and postprandial plasma from male participants and sad tears and saline, which was trickled below the eyelids, from female volunteers. These samples were then randomly distributed to male participants to sniff with a band-aid containing 100 µl of each fluid on four consecutive days in a double-blind fashion. We checked appetite by a visual analogue scale (VAS) and food intake by measuring the consumption of a test meal. In addition, the serum levels of total testosterone and LH were measured. Twenty men (mean age 26.3±4.6 years) were enrolled in this study. They could not discriminate between the smell of fasting and postprandial plasma and the smell of sad tears and trickled saline. Appetite and the amount of food intake were not different between the groups. Although the VAS ratings of appetite correlated with the food intake upon sniffing fasting plasma, postprandial plasma, and trickled saline, there was no such correlation upon sniffing sad tears. In addition, the decrease in serum testosterone levels from the baseline was greater with sad tears than with the trickled saline (-28.6±3.3% vs. -14.0±5.2%; P = 0.019). These data suggest that chemosignals from human sad tears and postprandial plasma do not appear to reduce appetite and food intake. However, further studies are necessary to examine whether sad tears may alter the appetite-eating behavior relation.
PLoS ONE 01/2012; 7(8):e42352. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Gestational diabetes mellitus (GDM) is known to increase the risk of cardiovascular diseases. Measuring the carotid artery intimal-medial thickness (CIMT) is a non-invasive technique used to evaluate early atherosclerosis and to predict future cardiovascular diseases. We examined the association between CIMT and cardiovascular risk factors in young Korean women with previous GDM.
One hundred one women with previous GDM and 19 women who had normal pregnancies (NP) were recruited between 1999 and 2002. At one year postpartum, CIMT was measured using high-resolution B-mode ultrasonography, and oral glucose tolerance tests were performed. Fasting glucose, glycated hemoglobin A1c (HbA1c), insulin levels and lipid profiles were also measured. CIMTs in the GDM and NP groups were compared, and the associations between CIMT and cardiovascular risk factors were analyzed in the GDM group.
CIMT results of the GDM group were not significantly different from those of the NP group (GDM, 0.435±0.054 mm; NP, 0.460±0.046 mm; P=0.069). In the GDM group, a higher HbA1c was associated with an increase in CIMT after age adjustment (P=0.011). CIMT results in the group with HbA1c >6.0% were higher than those of the normal HbA1c (HbA1c ≤6.0%) (P=0.010). Nine of the patients who are type 2 diabetes mellitus converters within one year postpartum but showed no significant difference in CIMT results compared to NP group.
Higher HbA1c is associated with an increase in CIMT in women with previous GDM. However, CIMT at one year postpartum was not increased in these women compared to that in NP women.
[show abstract][hide abstract] ABSTRACT: We assessed the predictive parameters for therapeutic efficacy of initial combination therapy with sitagliptin and metformin in drug-naïve type 2 diabetic patients. DeSIGN, PATIENTS, AND MEASUREMENTS: In this 52-week treatment study, 150 patients (mean age, 54·9 ± 12·5 years) with type 2 diabetes and HbA1c of 7·0-10% were treated with sitagliptin 100 mg once and metformin 500 mg twice daily. To assess the predictive parameters for therapeutic efficacy, a multivariate regression analysis was performed with baseline fasting glucose, insulin, C-peptide, and glucagon levels, homoeostasis model assessment-insulin resistance (HOMA-IR) and β-cell function (HOMA-B), insulinogenic index (IGI, defined as 30-0 min insulin/30-0 min glucose), and area under the curve for glucose, insulin, and C-peptide obtained after 75-g oral glucose tolerance test.
After 52 weeks, mean HbA1c levels and fasting and postload 2-h glucose were significantly decreased from 8·7 ± 1·4% to 7·2 ± 1·3%, 9·2 ± 3·0 to 7·2 ± 1·8 mm, and 17·5 ± 5·1 to 10·9 ± 3·6 mm, respectively (P < 0·01). HOMA-B and IGI increased significantly from 50·3 ± 33·5 to 75·1 ± 32·8 and from 11·3 ± 1·3 to 35·0 ± 6·3 at 52 weeks, respectively (P < 0·01). Multivariate regression analysis indicated that the reduction in HbA1c was significantly associated with high baseline HbA1c, low IGI, and short duration of diabetes after adjusting for age, sex, body mass index, blood pressure, triglycerides, creatinine, high-sensitivity CRP, glucagon, C-peptide, HOMA-B, and HOMA-IR. No severe adverse events were observed.
These results suggest that drug-naïve type 2 diabetic patients with low β-cell function would benefit the most from early initial combination therapy of sitagliptin and metformin.
[show abstract][hide abstract] ABSTRACT: To investigate the prevalence and severity of subclinical coronary atherosclerosis and plaque characteristics in asymptomatic subjects according to the presence or absence of metabolic syndrome (MS) with multidetector computed tomography (CT).
This study was approved and the requirement for informed patient consent was waived by the local institutional review board. Degree of coronary artery stenosis, multivessel involvement, and plaque characteristics, as well as coronary artery calcium score (CACS), were assessed with 64-detector row CT in 3000 age- and sex-matched asymptomatic individuals (mean age, 50.2 years ± 8.9 [standard deviation]; age range, 30-79 years). Anthropometric and metabolic profiles were also measured. Multivariate logistic regression analyses were performed to identify variables related to coronary atherosclerosis and plaque types.
Subjects with MS had significant coronary artery stenosis (>50% stenosis), multivessel involvement, more positive remodeling, more atherosclerotic coronary segments, and higher CACS than subjects without MS (P < .01 for all). Mixed and noncalcified plaques were also more prominent in subjects with MS than in those without MS (14.2% ± 4.4 vs 7.6% ± 3.1 and 13.1% ± 4.3 vs 7.3% ± 2.8, respectively; P < .01 for both). After adjustment for confounding factors, MS was strongly associated with significant coronary artery stenosis, multivessel involvement, and mixed plaque.
Multidetector CT is useful in the early diagnosis and evaluation of subclinical coronary atherosclerosis in asymptomatic patients with MS; however, future prospective studies are needed to address the clinical implications of these findings.
[show abstract][hide abstract] ABSTRACT: 11β-Hydroxysteroid dehydrogenase type 1 (HSD11B1), which converts inactive glucocorticoid to active glucocorticoid, plays a critical role in the pathogenesis of visceral obesity, metabolic syndrome, and diabetes. Hexose-6-phosphate dehydrogenase (H6PD) supplies a crucial cofactor, reduced nicotinamide adenine dinucleotide phosphate (NADPH), which allows HSD11B1 to maintain reductase activity. The association of common SNPs in HSD11B1 [IVS3-29G/T (rs12086634), IVS4-11120A/G (rs1000283)] and H6PD [R453Q (rs6688832), P554L (rs17368528)], either separately or combined, with type 2 diabetes and metabolic syndrome was examined in 427 Korean subjects with type 2 diabetes and in 358 nondiabetic Korean subjects. HSD11B1 polymorphisms (rs12086634 and rs1000283) were associated with metabolic syndrome among type 2 diabetic subjects and an H6PD polymorphism (rs17368528) was a risk factor for metabolic syndrome in nondiabetic subjects. However, no significant association of these SNPs with type 2 diabetes and metabolic syndrome was found after considering the multiple comparisons in the total study population. In conclusion, HSD11B1 and H6PD polymorphisms may not be associated with type 2 diabetes and metabolic syndrome. Further investigation of the role of these gene polymorphisms on the pathogenesis of metabolic syndrome is required.
[show abstract][hide abstract] ABSTRACT: Optimal cut points of central obesity identifying subjects at risk for MetS were proposed ethnic-specifically, but have not been established yet. Of particular interest are the values for elderly persons, which have not been identified previously. We investigated the appropriate cut points of WC and VFA for elderly in a community-based cohort in Korea. We recruited 294 men and 313 women aged 65 or over who participated in the KLoSHA. A receiver operating characteristic (ROC) curve analysis was used to estimate the optimal cut points of WC and VFA indicative of MetS. The optimal cut points for predicting MetS were 87 cm for WC, 140 cm(2) for VFA in men, and 85 cm for WC, 100 cm(2) for VFA in women with the Youden index. Similar cut points were obtained with the closest-to-(0, 1) criterion except for VFA in men, which was 122 cm(2). When adjusted for age, exercise, smoking, and alcohol consumption, men with ≥122 cm(2) and women with ≥100 cm(2) of VFA had a higher risk of MetS than subjects with lower values. The cut points of VFA and WC at risk for MetS were higher in men than women. In this community-based elderly cohort, the optimal cut points of WC at risk for MetS were lower than the Western criteria. Compared with the cut points in middle-aged Koreans, the cut points for elderly were lower in men and similar in women.
Archives of gerontology and geriatrics 08/2011; 54(2):e29-34. · 1.36 Impact Factor
[show abstract][hide abstract] ABSTRACT: Serotonin is involved in appetite regulation and energy homeostasis. Recently, it has been reported that 5-hydroxytryptamine receptor 2B (Htr2b) and tryptophan hydroxylase 1 (Tph1) play major role in β-cell proliferation in mouse during pregnancy. We investigated the genetic association of HTR2B and TPH1 with risk of gestational diabetes mellitus (GDM) and measures of obesity, in 869 Korean GDM women and carefully selected 632 nondiabetic control subjects. Six single-nucleotide polymorphisms (SNPs) in HTR2B and ten SNPs in TPH1 were selected for genotyping according to their tagging status. Genetic variants in HTR2B and TPH1 were not associated with the risk of GDM. In GDM women, SNPs of TPH1 were significantly associated with weight gain during pregnancy. In nondiabetic controls, SNPs of TPH1 were associated with waist circumference and BMI. We also found that a variant of TPH1 (rs623580) was associated with BMI in a genome-wide association study comprised of 8,842 subjects. Although genetic variants in HTR2B and TPH1 were not associated with risk of GDM, we found significant association of these variants with measures of obesity. However, further replication studies in a different population are required to confirm our findings.
[show abstract][hide abstract] ABSTRACT: Abdominal fat accumulation is known to be strongly implicated in development of metabolic syndrome (MetS). We examined diagnostic values of obesity-related parameters in 95 men and 185 women, and we determined optimal cutoff values of visceral fat area (VFA) and waist circumference (WC) for predicting the presence of multiple non-adipose components of MetS. Receiver operating characteristic (ROC) curve analysis revealed that VFA was the best indicator of MetS. WC and VFA exhibited similar diagnostic values for men and postmenopausal women, whereas WC was inferior to VFA for premenopausal women (area under ROC curve of VFA and WC was 0.76 and 0.52, respectively; P < 0.001). Optimal cutoff points of VFA and WC for predicting MetS were 136 cm(2) and 89 cm in men and 95 cm(2) and 82 cm in women, respectively. Subjects with VFA and WC above these cutoff values exhibited increased insulin resistance and increased carotid intima-media thickness. In conclusion, WC has a diagnostic value similar to VFA for predicting MetS in men and postmenopausal women, but not in premenopausal women. Further studies are necessary to develop a simple clinical parameter that reflects visceral fat in premenopausal women.
Journal of Korean medical science 07/2011; 26(7):906-13. · 0.84 Impact Factor