Effects of Sodium-Glucose Cotransporter 2 Inhibitors on Transcription Regulation of AgRP and POMC Genes.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors regulate plasma glucose levels in patients with type 2 diabetes mellitus (T2DM) by inhibiting renal glucose reabsorption. This study investigated the impact of empagliflozin (EMPA), an SGLT2 inhibitor, on hypothalamic energy regulation. To directly investigate the role of SGLT2 inhibitors in the hypothalamus, we administered EMPA through intracerebroventricular (i.c.v.) injections into the murine ventricles. After dental cementing the i.c.v. cannula onto the skull, the mice were given 5 days to recover before receiving vehicle or EMPA (50 nM/2 µL) injections. In a high-fat diet (HFD)-induced obesity model, we determined the gene expression levels of agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) in the hypothalamus. Additionally, we assessed FoxO1 expression, which regulates AgRP and POMC gene transcription in hypothalamic cell lines. We found that EMPA directly influenced the expression of endogenous mRNA of POMC and AgRP, which are critical for energy homeostasis, and modulated their transcription in high-fat diet-induced obese mice. Additionally, EMPA affected the expression of FoxO1, a key transcriptional regulator of glucose homeostasis, thereby regulating the transcriptional activity of POMC and AgRP. These results indicate that EMPA significantly influences hypothalamic energy homeostasis, highlighting its potential as a regulator in obesity and T2DM management.

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.

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.

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.

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.

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.

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.

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.

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.

Hyperhomocysteinaemia as a potential marker of early renal function decline in middle-aged Asian people without chronic kidney disease.

PURPOSE: High levels of serum total homocysteine (tHcy), often observed in chronic kidney disease (CKD) patients, are a risk factor for cardiovascular disease. However, little is known about the relationship between tHcy and renal function in healthy individuals. We examined whether tHcy levels are related to renal function in Asian individuals without CKD. METHODS: This cross-sectional study examined 2032 subjects, aged 40-64 years. Individuals with kidney diseases or other conditions that could affect tHcy were excluded. Renal function was determined by estimated glomerular filtration rate (eGFR) from levels of serum creatinine (sCr) and cystatin C. RESULTS: Age, tHcy, sCr, and cystatin C of the subjects were 54.1 ± 6.0 years, 9.5 (8.0-11.4) µmol/L, 0.81 ± 0.1 mg/dL, and 0.82 ± 0.1 mg/L, respectively. In a multiple linear regression analysis, tHcy was a significant independent determinant of sCr and cystatin C in men (ß = 0.206 and ß = 0.282, respectively) and women (ß = 0.247 and ß = 0.229, respectively). Highest tHcy levels were independently associated with increased cystatin C (>s1.10 mg/L) with an odds ratio (OR) of 5.00 [95% confidence interval (CI) 2.81-8.09] and decreased eGFR (<90 mL/min/1.73 m(2)) with an OR of 1.69 (95% CI 1.36-2.11) compared to tHcy levels in the 1st-3rd quartiles. CONCLUSIONS: Higher levels of tHcy are independently associated with sCr and cystatin C elevation. Our study suggests that tHcy levels may be influenced by renal function in Asian populations without CKD. Future studies are needed to define the role of tHcy in renal function.

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.

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.

Low serum TNF-related apoptosis-inducing ligand (TRAIL) levels are associated with acute ischemic stroke severity.

BACKGROUND: TNF-related apoptosis-inducing ligand (TRAIL) is a member of the tumor necrosis factor receptor superfamily and its serum level is known to be closely associated with future cardiovascular events and prognosis of various cardiovascular diseases. We investigated whether serum TRAIL levels are associated with the severity of acute ischemic stroke and specific stroke subtype. METHODS: We used an enzyme-linked immunosorbent assay to measure the serum TRAIL levels of 293 patients with acute ischemic stroke within 7 days of onset. Stroke subtype was classified as large artery atherosclerosis, cardioembolism, small vessel occlusion and other determined etiology. We used National Institute of Health Stroke Scale (NIHSS) score of first hospital day and stroke volume on diffusion-weighted imaging within 7 days of stroke onset for measuring the severity of acute ischemic stroke. RESULTS: The level of serum TRAIL showed significant negative correlations with NIHSS score and stroke volume. Serum TRAIL levels significantly decreased as the tertile of NIHSS score and stroke volume increased. The relative risk of patients with serum TRAIL<64.0 pg/mL for the presence of highest tertile of NIHSS score was significantly increased (adjusted OR [95%CI]; 7.07 [3.64-13.74]). Regarding stroke volume, the relative risk of patients with serum TRAIL<71.5 pg/mL for the presence of highest tertile of stroke volume was also significantly increased (adjusted OR [95%CI]; 2.81 [1.61-4.92]). There are no significant differences of serum TRAIL level among stroke subtypes. CONCLUSIONS: Low serum TRAIL levels were significantly associated with the acute ischemic stroke severity. This finding suggests that serum TRAIL might also have a role in acute ischemic stroke as well as other cardiovascular diseases.

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.

Comparison of serum ferritin and vitamin d in association with the severity of nonalcoholic Fatty liver disease in korean adults.

BACKGROUND: Increased serum ferritin and decreased vitamin D levels associated with nonalcoholic fatty liver disease (NAFLD). However, their association with the severity of NAFLD has not been fully evaluated. The aim of this study was to compare the association of serum ferritin and 25(OH)D3 levels with the severity of ultrasonographically detected NAFLD (US-NAFLD) and hepatic steatosis defined by fatty liver index (FLI) in Korean adults. METHODS: A cross-sectional analysis of clinical and anthropometric data, including serum ferritin and 25(OH)D3, from men (n=295) and women (n=263) who underwent a routine health check-up in 2012. RESULTS: In men, with an increase in the quartile of serum ferritin level, the incidences of subjects with metabolic syndrome (P=0.002), US-NAFLD (P=0.041), and FLI ≥60 (P=0.010) were significantly elevated. In women, the incidence of subjects with US-NAFLD was also significantly elevated with increases in the serum ferritin quartile (P=0.012). Regarding 25(OH)D3, no statistical differences were observed among the different quartiles in either gender. Serum ferritin level significantly increased as the severity of US-NAFLD increased (P<0.001); however, no significant differences in 25(OH)D3 level were observed in men. No significant differences in either serum ferritin or 25(OH)D3 level were observed among women with different levels of severity of US-NAFLD. CONCLUSION: Increased serum ferritin level showed a closer association with severity of NAFLD compared with level of serum vitamin D, suggesting that serum ferritin level may be a better marker than vitamin D level for predicting the severity of US-NAFLD and hepatic steatosis in a clinical setting.