Atrial fibrillation (AF) is prevalent in patients with type 2 diabetes mellitus (T2DM). Obesity commonly accompanies T2DM, and increases the risk of AF. However, the dose-relationship between body ...mass index (BMI) and AF risk has seldom been studied in patients with diabetes.
This cohort study utilized a database from National Taiwan University Hospital, a tertiary medical center in Taiwan. Between 2014 and 2019, 64,339 adult patients with T2DM were enrolled for analysis. BMI was measured and categorized as underweight (BMI < 18.5), normal (18.5 ≤ BMI < 24), overweight (24 ≤ BMI < 27), obesity class 1 (27 ≤ BMI < 30), obesity class 2 (30 ≤ BMI < 35), or obesity class 3 (BMI ≥ 35). Multivariate Cox regression and spline regression models were employed to estimate the relationship between BMI and the risk of AF in patients with T2DM.
The incidence of AF was 1.97 per 1000 person-years (median follow-up, 70.7 months). In multivariate Cox regression, using normal BMI as the reference group, underweight (HR 1.52, 95% CI 1.25-1.87, p < 0.001) was associated with a significantly higher risk of AF, while overweight was associated with significantly reduced risk of AF (HR 0.82, 95% CI 0.73-0.89, p < 0.001). Kaplan-Meier analysis showed AF risk was highest in the underweight group, followed by obesity class 3, while the overweight group had the lowest incidence of AF (log-rank test, p < 0.001). The cubic restrictive spline model revealed a "J-shaped" or "L-shaped" relationship between BMI and AF risk.
Underweight status confers the highest AF risk in Asian patients with T2DM.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Adipocyte fatty acid binding protein (A-FABP) is associated with atherosclerosis, and endothelial dysfunction is one of the reasons for adverse cardiovascular outcomes in patients undergoing ...hemodialysis (HD). This study investigated the correlation between serum A-FABP levels and endothelial function in HD patients. Fasting blood samples were collected from 90 HD patients. A-FABP levels were measured using a commercial enzyme immunoassay kit. Endothelial function was evaluated by a digital thermal monitoring test to measure vascular reactivity index (VRI). VRI < 1.0, 1.0 ≤ VRI < 2.0, and VRI ≥ 2.0 indicated poor, intermediate, and good vascular reactivity, respectively. In total, 14 (15.6%), 38 (42.2%), and 38 (42.2%) HD patients had poor, intermediate, and good VRI, respectively. Patients with poor VRI had lower pre-HD and post-HD body weight, body mass index, and serum creatinine level but higher serum A-FABP level (
= 0.001) than those with intermediate and good VRI. Log-transformed VRI (log-VRI) positively correlated with serum creatinine and negatively correlated with A-FABP by multivariate linear regression analysis. We concluded that A-FABP correlated with endothelial dysfunction in chronic HD patients.
Osteoprotegerin (OPG), a potent osteoclast activation inhibitor, decreases bone resorption and plays a role in mediating bone mineral density (BMD). Our aim was to evaluate the relationship between ...BMD and serum OPG in maintenance hemodialysis (MHD) patients.
Fasting blood samples were obtained from 75 MHD patients. BMD was measured by dual-energy X-ray absorptiometry in lumbar vertebrae (L2-L4). The WHO classification criteria were applied to define osteopenia and osteoporosis. A commercial enzyme-linked immunosorbent assay was used to measure serum OPG values.
Among all MHD patients, seven (9.3%) and 20 patients (26.7%) were defined as osteoporosis and osteopenia, respectively. Female patients had lower lumbar BMD than males (
= 0.002). Older age (
= 0.023), increased serum OPG (
< 0.001) urea reduction rate (
= 0.021), Kt/V (
= 0.027), and decreased body mass index (
= 0.006) and triglycerides (
= 0.020) were significantly different between the normal, osteopenia, and osteoporosis groups. Lumbar spine BMD was positively correlated with body mass index (BMI) (
< 0.001) but negatively correlated with OPG (
< 0.001) and age (
= 0.003). After grouping patients into T scores < -1 and < -2.5, female sex and OPG (adjusted odds ratio aOR 1.022, 95% confidence interval C.I. 1.011-1.034,
< 0.001) were predictors of T scores < -1, whereas only OPG was predictive of T scores < -2.5 (aOR 1.015, 95% C.I. 1.005-1.026,
= 0.004) by multivariate stepwise logistic regression analysis. The areas under the curve for predicting T scores < -1 or < -2.5 were 0.920 (95% C.I. 0.834-0.970,
< 0.001) and 0.958 (95% C.I. 0.885-0.991,
< 0.001), respectively.
Increased serum OPG negatively correlated with lumbar BMD and could be a potential biomarker predictive of osteoporosis in MHD patients.
p-Cresyl sulfate (PCS) is a uremic toxin that causes cardiovascular injury and progression in patients with chronic kidney disease (CKD). Peripheral arterial stiffness (PAS) as measured using the ...brachial-ankle pulse wave velocity (baPWV) is considered a valuable predictor of cardiovascular event risk in the general population. The study investigated the correlation between serum PCS levels and PAS (baPWV > 18.0 m/s) in 160 patients with stage 3−5 CKD. Liquid chromatography−mass spectrometry was used to assay serum PCS levels. PAS was detected in 54 patients (33.8%), and it was linked to older age, a higher prevalence of hypertension, higher systolic and diastolic blood pressure, higher serum calcium−phosphorus product and PCS levels, and lower height and body weight. Multivariable logistic regression analysis for independent factors associated with PAS illustrated that, in addition to age and diastolic blood pressure, serum PCS levels exhibited an odds ratio (OR) of 1.098 (95% confidence interval = 1.029−1.171, p = 0.005). These findings demonstrated that serum PCS levels were associated with PAS among patients with stage 3−5 CKD.
The role of indoxyl sulfate (IS), an important protein-bound uremic toxin, in arterial stiffness (AS) in patients with chronic kidney disease (CKD) is unclear.
We investigated the association between ...serum IS levels and AS in a cross-sectional study of 155 patients with CKD. Patients in the AS group was defined as carotid-femoral pulse wave velocity (cfPWV) value >10 m/s measured by a validated tonometry system (SphygmoCor), while values ≤10 m/s were regarded as without AS group Serum IS was measured by liquid chromatography-mass spectrometry analysis.
Of these CKD patients, AS was present in 51 (32.9%) patients, who were older, had a higher rate of diabetes, higher systolic blood pressure (SBP), and higher IS levels compared to those without AS. By multivariable logistic regression analysis, IS (adjusted odds ratio aOR 1.436, 95% confidence interval CI 1.085-1.901, p = 0.011), age (aOR 1.058, 95% CI 1.021-1.097, p = 0.002), and SBP (aOR 1.019, 95%CI 1.000-1.038, p = 0.049) were independent predictors of AS. By multivariable stepwise linear regression analysis, logarithmically transformed IS, age, DM, and SBP were significantly correlated with cfPWV. The area under the receiver-operating characteristic curve for serum log-IS was 0.677 (95%CI 0.598-0.750, p = 0.0001) to predict the development of AS in patients with CKD.
These finding demonstrate that in addition to older and higher SBP, a high serum IS level is a significant biomarker associated with AS in patients with CKD.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Angiopoietin-like protein 3 (ANGPTL3) plays an important role in lipid and lipoprotein trafficking and metabolism and is positively correlated with cardiovascular disease. Our objective was to ...evaluate the association between serum ANGPTL3 levels and endothelial function in patients on maintenance hemodialysis (MHD). We enrolled 116 patients on MHD and obtained their blood test results from their medical records. Using a noninvasive digital thermal monitor, we determined the vascular reactivity index (VRI) as a measure of endothelial function. Serum ANGPTL3 concentration was measured by a commercial-enzyme-linked immunosorbent assay. Vascular reactivity was classified as poor in 17 (14.7%) patients, intermediate (1.0 ≤ VRI < 2.0) in 50 (43.1%) patients, and high (VRI ≥ 2.0) in 49 (42.2%) patients. Serum levels of ANGPTL3 (
< 0.001) and alkaline phosphatase (ALP,
= 0.025) increased significantly as the VRI decreased. The log-transformed serum ALP (log-ALP,
= -0.187,
= 0.045) and log-ANGPTL3 (
= -0.319,
< 0.001) showed a negative correlation with the VRI on univariate linear regression analysis. A significant negative correlation was found between log-ANGPTL3 and VRI (
< 0.001) on multivariate stepwise linear regression analysis. The findings of our investigation showed that, in patients with MHD, the ANGPTL3 concentration had a negative correlation with the VRI.
Sarcopenia is highly prevalent in patients with advanced chronic kidney disease (CKD), yet a reliable serum index has not been established. The product of serum creatinine and the estimated ...glomerular filtration rate based on cystatin C (Cr×eGFRcys) was recently proposed as a sarcopenia index (SI), approximately to 24-h filtered creatinine through the glomerulus. We aimed to evaluate the diagnostic validity of the novel SI in advanced CKD. In 297 patients with non-dialysis stage 3b-5 CKD, aged 68.8 ± 12.9 years, the total skeletal muscle mass (SMM), handgrip strength (HGS), and usual gait speed were assessed. Sarcopenia was defined based on the Asian Working Group for Sarcopenia 2019 consensus update. The prevalence of sarcopenia in this cohort was 20.2%. The SI correlated moderately with SMM (
= 0.503,
< 0.001), HGS (
= 0.508,
< 0.001), and gait speed (
= 0.381,
< 0.001); the independency of the SI with three muscle metrics was confirmed after extensive adjustment. For sarcopenia prediction, the SI had acceptable discriminative powers in males area under the receiver operating characteristic curve (AUC) 0.646, 95% confidence interval (CI) 0.569-0.718 and females (AUC 0.754, 95% CI 0.670-0.826). In males, the best cut-off was 53.9, which provided 71.1% sensitivity, 58.0% specificity, 32.9% positive predictive value (PPV), and 87.4% negative predictive value (NPV); in females, the best cut-off was 45.8, which provided 81.8% sensitivity, 62.3% specificity, 31.0% PPV, and 94.3% NPV. In conclusion, Cr×eGFRcys could be served as a surrogate marker for sarcopenia and may be helpful for sarcopenia screening in advanced CKD. Further studies are needed to expand our investigation.
TAR DNA-binding protein 43 (TDP-43) has been identified as the major ubiquitinated aggregates in the inclusion bodies in the patients of amyotrophic lateral sclerosis (ALS) since 2006 and become a ...crucial culprit for ALS and related motor neuron diseases. Recent literature has further indicated that the major components of these aggregates are hyper-phosphorylated TDP-43 C-terminus. In an effort to clarify the conformational and physical properties of its disordered C-terminal domain, we have synthesized several peptide fragments and shown that only D1 within D1−4 can form twisted fibrils with a cross section of ∼11 nm in width under the incubation of phosphate buffer. In contrast, the D2−4 peptides all formed amorphous aggregates, showing different aggregation propensities. In addition to D1, two pathological mutant peptides, A315T and G294A, can also form fibrils that share similar shape and morphology with neuronal cytoplasmic inclusions. We propose that the residues with this region (287−322), which contains myriads of glycine repeats, may contribute significantly to the fiber formation as well as aggregation propensity. Moreover, from the conformational characterizations of D1, A315T, and G294A with EM, CD, fluorescence, and Raman spectroscopy, we found that all three peptides formed an amyloid structure, providing insights into the nature of its aggregation vis a vis the other fragments in the C-terminus of TDP-43.
Background and Objectives: Sclerostin and Dickkopf-1 (DKK1) modulate osteoblastogenesis, but their role in bone loss in hemodialysis (HD) patients is inconclusive. This study investigated ...relationships among lumbar bone mineral density (BMD), serum sclerostin, and DKK1 in HD patients. Materials and Methods: Blood samples were obtained from 75 HD patients. Dual-energy X-ray absorptiometry measured lumbar BMD of the lumbar vertebrae (L2−L4). Enzyme-linked immunosorbent assay revealed serum sclerostin and DKK1 concentrations. Results: There were 10 (13.3%), 20 (26.7%), and 45 (60%) patients defined as presenting with osteoporosis, osteopenia, or normal BMD, respectively. Age, alkaline phosphatase, urea reduction rate, fractional clearance index for urea, sclerostin level, and percentage of female patients are significantly negatively associated with the lumbar BMD and T-score, while the body mass index and waist circumference significantly positively associated with the lumbar BMD and T-score. Multivariate forward stepwise linear regression analysis indicated that serum sclerostin (β = −0.546, adjusted R2 change = 0.454; p < 0.001), age (β = −0.216, adjusted R2 change = 0.041; p = 0.007), and percentage of female HD patients (β = −0.288, adjusted R2 change = 0.072; p = 0.0018) were significantly negatively associated with lumbar BMD in HD patients. Conclusions: Advanced age, female gender, and serum sclerostin level, but not DKK1, were negatively associated with BMD in HD patients.
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