Long Term Effect of High Glucose and Phosphate Levels on the OPG/RANK/RANKL/TRAIL System in the Progression of Vascular Calcification in rat Aortic Smooth Muscle Cells.

Osteoprotegerin (OPG), receptor activator of NF-κB ligand (RANKL)/receptor activator of NF-κB (RANK) axis, and TNF-related apoptosis-inducing ligand (TRAIL) participate in vascular calcification process including atherosclerosis, but their contributions under high glucose (HG) and phosphate (HP) condition for a long-term period (more than 2 weeks) have not been fully determined. In this study, we evaluated the effects of HG and HP levels over 2 or 4 weeks on the progression of vascular calcification in rat vascular smooth muscle cells (VSMCs). Calcium deposition in VSMCs was increased in medium containing HG (30 mmol/L D-glucose) with ß-glycerophosphate (ß-GP, 12 mmol/L) after 2 weeks and increased further after 4 weeks. OPG mRNA and protein expressions were unchanged in HG group with or without ß-GP after 2 weeks. However, after 4 weeks, OPG mRNA and protein expressions were significantly lower in HG group with ß-GP. No significant expression changes were observed in RANKL, RANK, or TRAIL during the experiment. After 4 weeks of treatment in HG group containing ß-GP and rhBMP-7, an inhibitor of vascular calcification, OPG expressions were maintained. Furthermore, mRNA expression of alkaline phosphatase (ALP), a marker of vascular mineralization, was lower in the presence of rhBMP-7. These results suggest that low OPG levels after long term HG and phosphate stimulation might reduce the binding of OPG to RANKL and TRAIL, and these changes could increase osteo-inductive VSMC differentiation, especially vascular mineralization reflected by increased ALP activity during vascular calcification.

Multiple hypointense vessels on susceptibility-weighted imaging in acute ischemic stroke: surrogate marker of oxygen extraction fraction in penumbra?

BACKGROUND: Multiple hypointense vessels (MHV) on susceptibility-weighted imaging (SWI) are frequently observed in patients with acute cerebral ischemia, but their implication has not been clearly established. To elucidate the clinical significance of MHV on SWI, we investigated the association of MHV on SWI with clinical data and other MR markers in patients with acute ischemic stroke. METHODS: We enrolled acute stroke patients with internal carotid or proximal middle cerebral artery occlusion who underwent MRI including SWI within 3 days from stroke onset. Baseline clinical data were reviewed. Stroke severity was measured by the National Institutes of Health Stroke Scale (NIHSS). We graded the degree of MHV on SWI as four groups of none, subtle, relative, or extensive by the modified Alberta Stroke Program Early CT Scan (ASPECTS) system. To evaluate the degree of collateral flow, distal hyperintense vessels (DHV) on FLAIR and vessels on post-contrast time-of-flight MR angiography (TOF MRA) source images were graded respectively as 3 groups: none/subtle/prominent and poor/moderate/good. Diffusion and perfusion lesion volume and diffusion-perfusion mismatch (DPM) ratio were measured in all patients. We analyzed the association of the degree of MHV on SWI with clinical data and MR markers. RESULTS: Eighty patients were included in the study. The mean MR time from stroke onset was 12.4 h (range 0.5-63.0). There is no difference in MR time from stroke onset between groups of MHV on SWI. MHV were observed in 68 (85%) of 80 patients: none in 12, subtle in 11, relative in 13, and extensive in 44. There were no statistically significant associations between MHV on SWI and vascular risk factors. Patients with more extensive MHV on SWI had a smaller diffusion volume (p < 0.001), larger DPM (p < 0.001), and lower initial NIHSS scores (p = 0.022). Prominent DHV was presented in 29 of 44 patients with extensive MHV (p < 0.001). Good collateral flow on TOF MRA source images was presented in 37 of 44 patients with extensive MHV (p < 0.001). CONCLUSIONS: More extensive MHV on SWI in acute ischemic stroke is associated with lower initial NIHSS scores, smaller diffusion lesion volume, better collateral flow, and larger DPM. Our results show the possibility that MHV on SWI may be a useful surrogate marker for predicting increased oxygen extraction fraction and diffusion-perfusion mismatch in acute ischemic hemisphere.

Triglyceride-glucose index predicts type 2 diabetes mellitus more effectively than oral glucose tolerance test-derived insulin sensitivity and secretion markers.

AIMS: We explored the role of the triglyceride-glucose (TyG) index as an early and superior predictor of type 2 diabetes mellitus (T2DM) in individuals with normal glucose tolerance (NGT) using a community-based Korean cohort over 18 years. METHODS: We retrospectively examined 6,072 adults with NGT from the Korean Genome and Epidemiology Study. Cox proportional hazard regression models were employed to evaluate the risk of incidence of T2DM and receiver operating characteristic analysis was used to calculate the area under the curve (AUC). RESULTS: At baseline, the TyG index correlated with the homeostasis model assessment of insulin resistance (HOMA-IR) and the composite insulin sensitivity index (ISI) (ß: 0.045, p < 0.001; ß: -0.105, p < 0.001, respectively). Over the 18-year follow-up period, 999 individuals developed T2DM. An increase in the TyG quartile independently predicted the incidence of T2DM [hazard ratio, 2.36 (1.9-2.93) for Q4]. The AUC value of the TyG index was 0.642, the highest value among HOMA-IR and OGTT-derived insulin sensitivity and secretion markers. CONCLUSIONS: The TyG index is associated with HOMA-IR and composite ISI even with NGT. The TyG index demonstrated independent predictability for T2DM incidence in individuals with NGT, better than OGTT-derived insulin sensitivity and secretion markers.

The Ratio of Estimated Glomerular Filtration Rate Based on Cystatin C and Creatinine Reflecting Cardiovascular Risk in Diabetic Patients.

BACKGROUND: The ratio of estimated glomerular filtration rate (eGFR) based on cystatin C and creatinine (eGFRcystatin C/eGFRcreatinine ratio) is related to accumulating atherosclerosis-promoting proteins and increased mortality in several cohorts. METHODS: We assessed whether the eGFRcystatin C/eGFRcreatinine ratio is a predictor of arterial stiffness and sub-clinical atherosclerosis in type 2 diabetes mellitus (T2DM) patients, who were followed up during 2008 to 2016. GFR was estimated using an equation based on cystatin C and creatinine. RESULTS: A total of 860 patients were stratified according to their eGFRcystatin C/eGFRcreatinine ratio (i.e., <0.9, 0.9-1.1 [a reference group], and >1.1). Intima-media thickness was comparable among the groups; however, presence of carotid plaque was frequent in the <0.9 group (<0.9 group, 38.3%; 0.9-1.1 group, 21.6% vs. >1.1 group, 17.2%, P<0.001). Brachial-ankle pulse wave velocity (baPWV) was faster in the <0.9 group (<0.9 group, 1,656.3±333.0 cm/sec; 0.9-1.1 group, 1,550.5±294.8 cm/sec vs. >1.1 group, 1,494.0±252.2 cm/sec, P<0.001). On comparing the <0.9 group with the 0.9-1.1 group, the multivariate-adjusted odds ratios of prevalence of high baPWV and carotid plaque were 2.54 (P=0.007) and 1.95 (P=0.042), respectively. Cox regression analysis demonstrated near or over 3-fold higher risks of the prevalence of high baPWV and carotid plaque in the <0.9 group without chronic kidney disease (CKD). CONCLUSION: We concluded that eGFRcystatin C/eGFRcreatinine ratio <0.9 was related to an increased risk of high baPWV and carotid plaque in T2DM patients, especially, those without CKD. Careful monitoring of cardiovascular disease is needed for T2DM patients with low eGFRcystatin C/eGFRcreatinine ratio.

Low relative hand grip strength is associated with a higher risk for diabetes and impaired fasting glucose among the Korean population.

OBJECTIVE: This study investigated the association between relative hand grip strength (HGS) and glycemic status, such as impaired fasting glucose (IFG) and diabetes, using data from the Korea National Health and Nutrition Examination Survey (KNHANES). METHODS: We performed a cross-sectional study using the data from the KNHANES of 27,894 individuals from 2014 to 2019. Relative HGS was defined as the absolute HGS divided by body mass index and divided into quartiles in men and women. Odds ratios (OR) for diabetes and IFG were calculated using multivariate logistic regression analysis. All analyses were stratified by sex, and subgroup analysis was age-stratified. RESULTS: The lowest relative HGS quartile had a significant increase in the risk for diabetes (men: OR 2.72, 95% confidence interval [CI] 2.12-3.50; women: OR 3.38, 95% CI 2.70-4.24) and IFG (men: OR 1.35, 95% CI 1.15-1.59; women: OR 1.60, 95% CI 1.40-1.84). The ORs for diabetes and IFG according to the decreasing quartiles of relative HGS gradually increased in both sexes (P for trend <0.001). ORs and 95% CI of the lowest relative HGS quartile for diabetes were higher in the younger age group than that of the older age group (men: 4.47 and 2.80-7.14 for young adults; 2.41 and 1.37-4.25 for older adults; women: 5.91 and 3.06-9.38 for young adults; 1.47 and 0.92-2.33 for older adults). ORs and 95% CI for IFG was similar with the trend of ORs for diabetes (men: 1.80 and 1.43-2.26 for young adults; 1.17 and 0.75-1.84 for older adults; women: 2.20 and 1.77-2.72 for young adults; 1.33 and 0.86-2.07 for older adults). CONCLUSION: Lower relative HGS was associated with a higher risk of not only diabetes but also IFG in both sexes. These trends were stronger in younger adults than in older adults.

Association between serum uric acid and relative hand grip strength in comparison with metabolic syndrome components.

Objectives: To investigate the association between serum uric acid (UA) and relative hand grip strength (HGS) in comparison with metabolic syndrome components. Methods: We analyzed the data of 5247 Korean adults aged ≥ 20 years (2422 men and 2825 women) who participated in the KNHNES VII (2018). Results: Among women, relative HGS was significantly lower in participants with hyperuricemia (1.65 ± 0.04) than in those without (1.95 ± 0.01) and was significantly decreased in the highest quartile (4Q: 1.77 ± 0.02) of serum UA compared with that in the lowest quartile (1Q: 1.98 ± 0.02). Among men, relative HGS was lower in participants with hyperuricemia (3.09 ± 0.04 vs. 3.16 ± 0.02) and decreased in 4Q (3.08 ± 0.03) of serum UA compared with that in 1Q (3.15 ± 0.03); however, these results were not statistically significant. In age- and multivariate-adjusted analyses in men, relative HGS was significantly lower in 4Q compared with that in 1Q in model 1 (adjusted for age), but there were no significant differences in model 2 (adjusted for age, BMI, and waist circumference) and model 3 (adjusted for age, BMI, waist circumference, systolic and diastolic blood pressure, fasting blood glucose, triglycerides, and high-density lipoprotein cholesterol). Meanwhile, in women, relative HGS was significantly decreased in 4Q compared with that in 1Q in all models. Conclusions: A significant inverse correlation was observed between serum UA levels and relative HGS in women, and their significance was maintained even after adjusting for age and metabolic syndrome components.

Synergistic Interaction between Hyperuricemia and Abdominal Obesity as a Risk Factor for Metabolic Syndrome Components in Korean Population.

BACKGROUND: The present study investigated the role of synergistic interaction between hyperuricemia and abdominal obesity as a risk factor for the components of metabolic syndrome. METHODS: We performed a cross-sectional study using the data of 16,094 individuals from the seventh Korean National Health and Nutrition Examination Survey (2016 to 2018). The adjusted odds ratios of metabolic syndrome and its components were analyzed by multivariate logistic regression analysis. The presence of synergistic interaction between hyperuricemia and abdominal obesity was evaluated by calculating the additive scales-the relative excess risk due to interaction, attributable proportion due to interaction, and synergy index (SI). RESULTS: There was a synergistic interaction between hyperuricemia and abdominal obesity in hypertriglyceridemia (men: SI, 1.39; 95% confidence interval [CI], 1.01 to 1.98; women: SI, 1.61; 95% CI, 1.02 to 2.69), and low high-density lipoprotein cholesterol (HDL-C) (men: SI, 2.03; 95% CI, 1.41 to 2.91; women: SI, 1.70; 95% CI, 1.05 to 2.95). There was no significant synergistic interaction between hyperuricemia and abdominal obesity for the risk of high blood pressure (men: SI, 1.22; 95% CI, 0.85 to 1.77; women: SI, 1.53; 95% CI, 0.79 to 2.97), and hyperglycemia (men: SI, 1.03; 95% CI, 0.72 to 1.47; women: SI, 1.39; 95% CI, 0.75 to 2.57). CONCLUSION: Hyperuricemia and abdominal obesity synergistically increased the risk of hypertriglyceridemia and low HDL-C in both sexes.

Bone morphogenetic protein-7 inhibits vascular calcification induced by high vitamin D in mice.

Vascular calcification refers to the deposition of calcium phosphate in cardiovascular tissues, including arteries and myocardium. Vascular calcification is frequently associated with cardiovascular disease. Recently, bone morphgenetic protein-7 (BMP-7) has been proposed to play an inhibitory role in vascular calcification, but its inhibitory effect has not been fully elucidated. We therefore tested the hypothesis that BMP-7 inhibits vascular calcification by using two conditions, high levels of vitamin D and phosphate, each of which could enhance vascular calcification. C57BL/6 mice were treated for 3 days with high vitamin D (500,000 IU/kg/day) in the presence or absence of recombinant human BMP-7 (rhBMP-7). Expression levels of osteopontin and osteocalcin, markers of the osteoblastic phenotype, were assessed by immunohistochemical staining or Western blotting analysis. Vitamin D increased calcium staining in thoracic aortas and hearts and the expression levels of osteopontin and osteocalcin in mice. Importantly, pretreatment for 7 days and subsequent treatment for 3 days with rhBMP-7 (10 microg/kg/day) abolished the vitamin D-mediated increases in the above parameters. In addition, human aortic smooth muscle cells (HASMCs) were cultured with high beta-glycerophosphate, a phosphate donor, for 2 weeks in the presence or absence of rhBMP-7. High beta-glycerophosphate increased expression levels of osteopontin and osteocalcin as well as calcium staining in HASMCs, but these changes were attenuated by treatment with BMP-7. Thus, BMP-7 inhibits vascular calcification associated with high levels of vitamin D or phosphate. We propose that BMP-7 treatment may be helpful in reducing the risks of cardiovascular disease related to vascular calcification.

The prevalence of low triiodothyronine according to the stage of chronic kidney disease in subjects with a normal thyroid-stimulating hormone.

BACKGROUND: We hypothesized that the prevalence of low T3 would be increased according to the increase in CKD stage. This study was performed to explore the prevalence in each stage of CKD and relationship with eGFR. METHODS: A total of 2284 cases with normal thyroid-stimulating hormone (TSH) level were enrolled and retrospectively analysed during the recent period, from July 2005 to December 2007. RESULTS: There was an increasing trend for the population of low T3 according to the increase of a CKD stage (eGFR > or = 90, 8.2%; > or = 60 eGFR < 90, 10.9%; > or = 30 eGFR < 60, 20.8%; > or = 15 eGFR < 30, 60.6%; eGFR < 15, 78.6%). Also, there was positive relationship between eGFR and serum T3 in male, female and total subjects. After adjusting for age and sex, compared with eGFR > or = 60 ml/min/ 1.73 m2, eGFR < 60 ml/min/1.73 m2 was associated with an increased odds of low T3 [odds ratio 2.40 (CI: 1.5315 to 3.1731)]. In multiple regression analysis, eGFR was positively related with T3 (standardized coefficient 0.143, R2 = 0.055, P < 0.001), independent of age and serum albumin. CONCLUSION: This study showed that low T3 syndrome was highly prevalent in CKD and was a remarkable finding in early CKD. Furthermore, serum T3 levels were associated with severity of CKD even in the normal TSH level.

The fatty liver index, a simple and useful predictor of metabolic syndrome: analysis of the Korea National Health and Nutrition Examination Survey 2010-2011.

PURPOSE: Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide, and it is the hepatic manifestation of metabolic syndrome (MetS). We aimed to estimate the prevalence of NAFLD defined by the fatty liver index (FLI), in order to investigate the association between FLI and metabolic disorders and to determine the cutoff value of FLI to screen for MetS. SUBJECTS AND METHODS: This study utilized a national representative sample of Korean adults (the Korean National Health and Nutrition Examination Surveys) which was conducted in 2010-2011. A total of 10,107 adults aged 19 years or older were selected. NAFLD was diagnosed on the basis of an increased FLI (≥60) after the exclusion of alcohol or viral liver disease. RESULTS: NAFLD was identified in 1,134 subjects (age-standardized prevalence, 10.0%). When subjects were categorized into three groups by FLI (<20, 20-59, and ≥60), the higher FLI group showed a higher prevalence of hypertension (49.7% vs 14.4%), diabetes mellitus (DM; 20.4% vs 3.8%), and MetS (74.9% vs 7.4%). FLI was positively associated with age, body mass index, blood pressure, hemoglobin A1c, and homeostasis model assessment of insulin resistance (P for trend <0.001). In the multivariate analysis, the higher FLI group had a significantly higher risk for hypertension (OR =2.92, 95% CI =2.18-3.90, P<0.001), DM (OR =4.38, 95% CI =2.96-6.49, P<0.001), and MetS (OR =24.85, 95% CI =17.33-35.64, P<0.001). However, no increase was observed for cardiovascular disease after adjustment of other risk factors. The cutoff value of the FLI estimated to predict the presence of MetS was 20 (area under the curve 0.849, sensitivity 0.828, and negative predictive value 91.9%). CONCLUSION: NAFLD prevalence using FLI is significantly higher in subjects with metabolic disorder including MetS. FLI might be a useful screening tool to detect subjects who may require early management of MetS and who have a high cardiovascular risk.

Serum cystatin C is related to pulse wave velocity even in subjects with normal serum creatinine.

We hypothesized that serum cystatin C can be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based glomerular filtration rate (GFR). The aim of this study is to evaluate whether serum cystatin C is related to arterial stiffness independently of serum creatinine in subjects for whom serum creatinine is normal. A total of 2,018 individuals (1,120 males, 898 females) were enrolled. Mean brachial-ankle pulse wave velocity (baPWV) was used as a marker of arterial stiffness and sex-specific analysis was performed. A positive relationship between baPWV and serum cystatin C (Y=1109.0548+329.9102X, r(2)=0.056, p<0.001) was found in males. Stepwise multivariate regression analysis in males showed that age, waist circumference, heart rate, cystatin C level, triglyceride level, and fasting glucose were independent contributors to baPWV. In females, a positive relationship between baPWV and serum cystatin C (Y=1035.7828+402.2970X, r(2)=0.090, p<0.001) was found. Stepwise multivariate regression analysis showed that age, heart rate, cystatin C level, fasting glucose and insulin level were independent contributors to baPWV. Age, heart rate, fasting glucose and serum cystatin C were the significant variables in both genders that contributed to baPWV. In conclusion, this study confirmed that serum cystatin C was related to pulse wave velocity even in subjects with normal serum creatinine. This finding suggested that cystatin C could be a more predictable marker of arterial stiffness than serum creatinine and creatinine-based GFR.

Comparison of alanine aminotransferase, white blood cell count, and uric acid in their association with metabolic syndrome: a study of Korean adults.

The aim of this study is to investigate the respective associations of alanine aminotransferase (ALT), white blood cell (WBC) count, and uric acid with metabolic syndrome and compare the magnitude in their association with metabolic syndrome, using modified Adult Treatment Panel III (ATP III) and its components. We studies 5,020 Korean adults (20-70 years of age; 2,501 men and 2,519 women) who visited Center for Health Promotion in Pusan National University Hospital for routine health examinations. Metabolic parameters and biochemical markers including ALT, WBC count, and uric acid were obtained. Alcohol intake, smoking status, and the presence of fatty liver were also evaluated. The prevalence of metabolic syndrome was 17.3%. In the partial correlation coefficients adjusted for age, alcohol consumption, smoking status, and presence of fatty liver, ALT was correlated significantly with all components of metabolic syndrome among three markers in men and women respectively. Moreover, ALT showed the highest correlation with HOMA-IR (r=0.311, P<0.001 in men and r=0.285, P<0.001 in women) in both genders. With the increase in the number of metabolic syndrome components, the mean values of all three markers were also significantly increased. In addition, the adjusted mean values of each marker were all significantly increased in metabolic syndrome. In ALT, the adjusted mean values were significantly increased in subjects with all metabolic component disorders. When we calculated odd ratios (ORs) for metabolic syndrome prevalence of the highest quartiles in three markers using multivariate logistic regression analyses, ALT was associated most strongly with metabolic syndrome in both genders (OR 5.65 [95% CI, 3.80 to 8.40]; P<0.001 in men, OR 3.23 [95% CI, 2.15 to 4.86]; P<0.001 in women). The cut-off value for ALT using the ROC curve was 27 IU/L (area under the curve=0.717, sensitivity 62.5%, specificity 70.4%, P<0.001) in men and 18 IU/L (area under the curve=0.735, sensitivity 61.3%, specificity 72.3%, P<0.001) in women. In conclusion, ALT, WBC count, and uric acid play important role as an additional markers for metabolic syndrome. Among three markers, in overlap the multiple risk factors, ALT might have a strong association with metabolic syndrome in Korean adults.

Relative handgrip strength as a marker of metabolic syndrome: the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2014-2015).

Purpose: Muscles play an important role in energy metabolism. Several studies have investigated the association between muscle mass and metabolic syndrome (MetS), reporting conflicting results. However, studies concerning the association between muscle strength and MetS are limited. We aimed to investigate the association between relative handgrip strength (HGS) and MetS in Korean adults. Participants and methods: We analyzed data from 5,014 Korean adults aged ≥20 years (2,472 men and 2,542 women) who participated in the Korea National Health and Nutrition Examination Survey (KNHANES) VI (2014-2015). Results: The increasing quartiles of relative HGS (defined as the sum of both hands' HGS divided by body mass index) were inversely associated with the risk of MetS in both men and women (OR, 0.37; 95% CI, 0.30-0.45, vs OR, 0.19; 95% CI, 0.14-0.27, respectively) after multivariable adjustment for age, region of residence, smoking status, heavy alcohol consumption, regular exercise, family income, and education level. On multivariable logistic regression analyses, participants with the highest relative HGS had a significant decrease in relative risk of MetS, compared with those with the lowest relative HGS. The multivariable-adjusted ORs (with 95% CIs) for MetS in quartiles 1, 2, 3, and 4 were 1.00, 0.72 (0.55-0.94), 0.34 (0.26-0.46), and 0.22 (0.15-0.32) in men and 1.00, 0.50 (0.36-0.68), 0.26 (0.17-0.40), and 0.16 (0.09-0.27) in women, respectively. Conclusion: Relative HGS showed a highly significant inverse association with the risk of MetS in Korean adults, and it can be a novel biomarker for assessing the risk of MetS.

The association of serum gamma glutamyltransferase with components of the metabolic syndrome in the Korean adults.

The metabolic syndrome (MS) is a cluster of risk factors for cardiovascular disease related to insulin resistance. Recently, serum gamma glutamyltransferase (GGT) has been proposed as a marker of oxidative stress and is associated with a marked increase in the risk of cardiovascular disease. So, we investigated the association between serum GGT and components of the metabolic syndrome in the Korean adults. A total 3246 adults (aged 20-70 years, 1622 men and 1624 women) who visited Center for Health Promotion in Pusan National University Hospital for a medical checkup were included. We measured serum GGT and lipid profiles, fasting glucose, fasting insulin and blood pressure. As the quartile of serum GGT increased, the number of components of MS and prevalence of MS were increased. Serum GGT was also increased according as the number of components of MS was increased. A significant correlation (r=0.200, p<0.001 in men and r=0.133, p<0.001 in women) was noted between the numbers of the components of the MS and serum GGT. In addition, serum GGT was correlated significantly (r=0.266, p<0.001 in men and r=0.264, p<0.001 in women) with homeostasis model assessment of insulin resistance (HOMA-IR). In linear regression model, serum GGT was mainly influenced by the concentration of triglycerides and fasting glucose. In conclusion, serum GGT is closely related with insulin resistance and the increased number of components of MS. Among components of MS, serum GGT may be more associated with dyslipidemia and abnormal glucose tolerance, suggesting that serum GGT has more relationship with hepatic insulin resistance regardless of non-alcoholic fatty liver disease.

Association between serum cystatin C and bone mineral density in Korean adults.

Background: Serum cystatin C has been known as a novel marker of preclinical renal dysfunction, and higher cystatin C levels are associated with increased risks of hip and nonvertebral fractures. However, there are few reports on the association between serum cystatin C and bone mineral density (BMD), especially in the Asian population. We evaluated the association between cystatin C levels and BMD of the spine and hip in Korean adults. Methods: A cross-sectional study was performed in 865 Korean adults (325 men and 540 women) who participated in a comprehensive medical examination program and underwent bone densitometry. Renal function was assessed by the estimated glomerular filtration rate (eGFR), which was calculated using an equation based on creatinine (eGFRcre) and cystatin C (eGFRcys). Results: The serum cystatin C level was negatively correlated with different types of BMD, including the lowest lumbar, total lumbar, femoral neck, and total femur BMD, in women, but not in men. Higher cystatin C levels were associated with a higher prevalence of osteoporosis in women (odds ratio [OR], 3.68; 95% confidence interval [CI], 1.69-8.03; P=0.001), but not in men (OR, 0.85; 95% CI, 0.30-2.38; P=0.761). However, this association was attenuated in the multivariable model adjusted for age, body mass index, serum 25-hydroxyvitamin D3, and creatinine (OR, 1.01; 95% CI, 0.38-2.71) in women. In addition, the eGFRcys showed a stronger positive correlation with BMD than the eGFRcre. Conclusion: Our findings suggest that serum cystatin C levels might help identify women with osteoporosis who are susceptible to fractures.

Characterization of follicular thyroid nodules at fine needle aspiration biopsy using double phase thallium-201 imaging: comparison of visual and semiquantitative analyses.

OBJECTIVE: To compare visual and semiquantitative indices of double phase thallium-201 thyroid scintigraphy (DTS) for differentiation of malignant nodules by indeterminate fine needle aspiration biopsy (FNAB) results. DESIGN: DTS (early; 15 minutes; delayed, 2 hour) were performed after injection of 37MBq of thallium-201 in 60 patients with indeterminate FNAB. MAIN OUTCOME: With grade 4 and 5, sensitivity and specificity were 51.4% and 78.3%, respectively. With early lesion to nonlesion ratio (L/N) 1.49, sensitivity and specificity were 97.3% and 39.1%, respectively. With delayed L/N 1.89, sensitivity and specificity were 70.3% and 78.3%, respectively. With wash-out rate (WR) 18.93%, sensitivity and specificity were 89.2% and 82.6%. Early L/N was superior to delayed L/N and WR for the detection of malignant thyroid nodules. CONCLUSION: Visual assessment had a limited value for differentiation of follicular nodules. The optimal semiquantitative indices were 1.49 for early L/N and 1.89 for delayed L/N. Also, optimal WR was 18.93%. The early L/N was superior to delayed L/N and WR for the detection of malignant thyroid nodular lesions. However, visual assessment and early L/N of DTS showed similar results. Visual analysis and semiquantitative indices of DTS could not differentiate follicular carcinoma and follicular variant of papillary thyroid cancer.

Prevalence of Reduced Kidney Function by Estimated Glomerular Filtration Rate Using an Equation Based on Creatinine and Cystatin C in Metabolic Syndrome and Its Components in Korean Adults.

BACKGROUND: It is known that metabolic syndrome (MetS) is associated with chronic kidney disease. We evaluated and compared the prevalence of reduced kidney function in MetS and its components by estimated glomerular filtration rate (eGFR) using an equation based on creatinine (eGFRcr), cystatin C (eGFRcys), and combined creatinine-cystatin C (eGFRcr-cys) in Korean adults. METHODS: We analyzed data from 3,649 adults who participated in a comprehensive health examination. RESULTS: Mean values of eGFRcys were higher compared with mean values of eGFRcr (96.1±18.2 mL/min/1.73 m² vs. 91.2±13.6 mL/min/1.73 m²) in total subjects. The prevalence of reduced kidney function increased with age (9.6% for eGFRcys vs. 5.8% for eGFRcr-cys vs. 4.9% for eGFRcr, in subjects aged ≥60 years), and significantly increased with MetS, abdominal obesity, hypertension, high triglyceride, low high density lipoprotein (HDL), and high insulin resistance. The prevalence of MetS, abdominal obesity, hypertension, high insulin resistance, low HDL, and hepatic steatosis was significantly increased in subjects with reduced kidney function. This increased prevalence and the odds ratio of reduced kidney function for prevalence of MetS was highest for eGFRcys, followed by those of eGFRcr-cys, and eGFRcr. CONCLUSION: The prevalence of reduced kidney function by eGFR was significantly increased in subjects with MetS and its related components. eGFRcys and eGFRcr-cys were superior to eGFRcr in detecting reduced kidney function.

Prevalent Rate of Nonalbuminuric Renal Insufficiency and Its Association with Cardiovascular Disease Event in Korean Type 2 Diabetes.

BACKGROUND: Nonalbuminuric renal insufficiency is a unique category of diabetic kidney diseases. The objectives of the study were to evaluate prevalent rate of nonalbuminuric renal insufficiency and to investigate its relationship with previous cardiovascular disease (CVD) event in Korean patients with type 2 diabetes mellitus (T2DM). METHODS: Laboratory and clinical data of 1,067 subjects with T2DM were obtained and reviewed. Study subjects were allocated into four subgroups according to the CKD classification. Major CVD events were included with coronary, cerebrovascular, and peripheral vascular events. RESULTS: Nonalbuminuric stage ≥3 CKD group, when compared with albuminuric stage ≥3 CKD group, had shorter diabetic duration, lower concentrations of glycated hemoglobin, high density lipoprotein cholesterol, and high-sensitivity C-reactive protein, lower prevalent rates of retinopathy and previous CVD, and higher rate of treatment with angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers. Nonalbuminuric stage ≥3 CKD group showed a greater association with prior CVD events than no CKD group; however, albuminuric stage ≥3 CKD group made addition to increase prevalence of prior CVD events significantly when CKD categories were applied as covariates. Association of prior CVD events, when compared with normal estimated glomerular filtration rate (eGFR) and nonalbuminuria categories, became significant for declined eGFR, which was higher for eGFR of <30 mL/min/1.73 m², and albuminuria. CONCLUSION: The results show that subjects with nonalbuminuric stage ≥3 CKD is significantly interrelated with occurrence of prior CVD events than those with normal eGFR with or without albuminuria. Comparing with normal eGFR and nonalbuminuria categories, the combination of increased degree of albuminuria and declined eGFR is becoming significant for the association of prior CVD events.

The Association of Serum Cystatin C with Glycosylated Hemoglobin in Korean Adults.

BACKGROUND: Cystatin C has been known to be associated not only with early renal impairment but also with the incidence of diabetic conditions (prediabetes plus diabetes). However, it is not clear whether cystatin C levels are associated with the prevalence of diabetic conditions in Asian populations. We evaluated this association using glycosylated hemoglobin (HbA1c) levels as the definition of diabetes in Korean adults. METHODS: We analyzed data from 1,559 Korean adults (937 men and 622 women) with available serum cystatin C and HbA1c values. RESULTS: The serum cystatin C levels in subjects with prediabetes and diabetes were significantly increased (0.91±0.14 mg/L in prediabetes and 0.91±0.17 mg/L in diabetes vs. 0.88±0.13 mg/L in patients with normal glucose levels, P=0.001). At increasing cystatin C levels, the prevalence of subjects with prediabetes (30.2% vs. 14.6%, P<0.001) and those with diabetes (10.6% vs. 8.0%, P<0.001) significantly increased in the group with the highest cystatin C levels. The group with the highest cystatin C levels had a significantly increased odds ratio (OR) for the presence of diabetic conditions compared to the group with the lowest values in total subjects (OR, 2.35; 95% confidence interval [CI], 1.54 to 3.58; P<0.001) and in women (OR, 4.13; 95% CI, 1.97 to 8.65; P<0.001), though there was no significant increase after adjusting for multiple variables. CONCLUSIONS: Higher levels of serum cystatin C are associated with an increased prevalence of diabetic conditions in Korean adults. Our findings may extend the positive association of cystatin C with diabetes incidence to an Asian population.