Plasma angiotensin-converting enzyme 2 (ACE2) is a marker for renal outcome of diabetic kidney disease (DKD) (U-CARE study 3).

INTRODUCTION: ACE cleaves angiotensin I (Ang I) to angiotensin II (Ang II) inducing vasoconstriction via Ang II type 1 (AT1) receptor, while ACE2 cleaves Ang II to Ang (1-7) causing vasodilatation by acting on the Mas receptor. In diabetic kidney disease (DKD), it is still unclear whether plasma or urine ACE2 levels predict renal outcomes or not. RESEARCH DESIGN AND METHODS: Among 777 participants with diabetes enrolled in the Urinary biomarker for Continuous And Rapid progression of diabetic nEphropathy study, the 296 patients followed up for 9 years were investigated. Plasma and urinary ACE2 levels were measured by the ELISA. The primary end point was a composite of a decrease of estimated glomerular filtration rate (eGFR) by at least 30% from baseline or initiation of hemodialysis or peritoneal dialysis. The secondary end points were a 30% increase or a 30% decrease in albumin-to-creatinine ratio from baseline to 1 year. RESULTS: The cumulative incidence of the renal composite outcome was significantly higher in group 1 with lowest tertile of plasma ACE2 (p=0.040). Group 2 with middle and highest tertile was associated with better renal outcomes in the crude Cox regression model adjusted by age and sex (HR 0.56, 95% CI 0.31 to 0.99, p=0.047). Plasma ACE2 levels demonstrated a significant association with 30% decrease in ACR (OR 1.46, 95% CI 1.044 to 2.035, p=0.027) after adjusting for age, sex, systolic blood pressure, hemoglobin A1c, and eGFR. CONCLUSIONS: Higher baseline plasma ACE2 levels in DKD were protective for development and progression of albuminuria and associated with fewer renal end points, suggesting plasma ACE2 may be used as a prognosis marker of DKD. TRIAL REGISTRATION NUMBER: UMIN000011525.

Reduced Immunogenicity of COVID-19 Vaccine in Obese Patients with Type 2 Diabetes: A Cross-Sectional Study.

The global pandemic of coronavirus infection 2019 (COVID-19) was an unprecedented public health emergency. Several clinical studies reported that heart disease, lung disease, diabetes, hypertension, dyslipidemia, and obesity are critical risk factors for increased severity of and hospitalization for COVID-19. This is largely because patients with these underlying medical conditions can show poor immune responses to the COVID-19 vaccinations. Diabetes is one of the underlying conditions most highly associated with COVID-19 susceptibility and is considered a predictor of poor prognosis of COVID-19. We therefore investigated factors that influence the anti-SARS-CoV-2 spike IgG antibody titer after three doses of vaccination in patients with type 2 diabetes. We found that obesity was associated with low anti-SARS-CoV-2 spike IgG antibody titers following three-dose vaccination in type 2 diabetics. Obese patients with type 2 diabetes may have attenuated vaccine efficacy and require additional vaccination; continuous infection control should be considered in such patients.

Molecular and cellular insights into auxin-regulated primary root growth: a comparative study of Arabidopsis and rice.

Auxin regulation of primary root growth in Arabidopsis and rice was compared by analyzing root growth in response to changes in auxin levels. A bell-shaped root-growth curve was identified in both Arabidopsis and rice in response to change in auxin levels. In Arabidopsis, cell division was the main regulator of root growth in response to auxin; in rice, auxin promoted root growth by regulating cell division and cell length. The expression levels of PLETHORA (PLT) genes in response to change in auxin level followed a bell-shaped curve and closely correlated with cell division in Arabidopsis but not in rice, implying that PLT gene expression plays key role to control root growth in Arabidopsis. The level of auxin in Arabidopsis was optimal for primary root elongation, while in rice it was higher than optimal. These differences may explain the species-dependent development of root systems.

Eleven years of data on the Jefferson Scale of Empathy - medical student version: Japanese norm data and tentative cutoff scores.

BACKGROUND: More and more studies investigate medical students' empathy using the Jefferson Scale of Empathy (JSE). However, no norm data or cutoff scores of the JSE for Japanese medical students are available. This study therefore explored Japanese norm data and tentative cutoff scores for the Japanese translation of the JSE-medical student version (JSE-S) using 11 years of data obtained from matriculants from a medical school in Japan. METHODS: Participants were 1,216 students (836 men and 380 women) who matriculated at a medical school in Japan from 2011 to 2021. The JSE-S questionnaire was administered to participants prior to the start of the program. Data were summarized using descriptive statistics and statistical tests were performed to show the norm data and tentative cutoff scores for male and female students separately. RESULTS: The score distributions of the JSE-S were moderately skewed and leptokurtic for the entire sample, with indices -0.75 and 4.78, respectively. The mean score (standard deviation) for all participants was 110.8 (11.8). Women had a significantly higher mean score (112.6) than men (110.0; p < 0.01). The effect size estimate of gender difference was 0.22, indicating a small effect size. The low and high cutoff scores for men were ≤ 91 and ≥ 126, respectively, and the corresponding scores for women were ≤ 97 and ≥ 128, respectively. CONCLUSIONS: This study provides JSE-S norm data and tentative cutoff scores for Japanese medical school matriculants, which would be helpful in identifying those who may need further training to enhance their empathy.

Methylglyoxal Induces Inflammation, Metabolic Modulation and Oxidative Stress in Myoblast Cells.

Uremic sarcopenia is a serious clinical problem associated with physical disability and increased morbidity and mortality. Methylglyoxal (MG) is a highly reactive, dicarbonyl uremic toxin that accumulates in the circulatory system in patients with chronic kidney disease (CKD) and is related to the pathology of uremic sarcopenia. The pathophysiology of uremic sarcopenia is multifactorial; however, the details remain unknown. We investigated the mechanisms of MG-induced muscle atrophy using mouse myoblast C2C12 cells, focusing on intracellular metabolism and mitochondrial injury. We found that one of the causative pathological mechanisms of uremic sarcopenia is metabolic flow change to fatty acid synthesis with MG-induced ATP shortage in myoblasts. Evaluation of cell viability revealed that MG showed toxic effects only in myoblast cells, but not in myotube cells. Expression of mRNA or protein analysis revealed that MG induces muscle atrophy, inflammation, fibrosis, and oxidative stress in myoblast cells. Target metabolomics revealed that MG induces metabolic alterations, such as a reduction in tricarboxylic acid cycle metabolites. In addition, MG induces mitochondrial morphological abnormalities in myoblasts. These changes resulted in the reduction of ATP derived from the mitochondria of myoblast cells. Our results indicate that MG is a pathogenic factor in sarcopenia in CKD.

Silica-associated systemic lupus erythematosus with lupus nephritis and lupus pneumonitis: A case report and a systematic review of the literature.

INTRODUCTION: Several epidemiological studies have shown that silica exposure triggers the onset of systemic lupus erythematosus (SLE); however, the clinical characteristics of silica-associated SLE have not been well studied. PATIENT CONCERNS: A 67-year-old man with silicosis visited a primary hospital because of a fever and cough. His respiratory condition worsened, regardless of antibiotic medication, and he was referred to our hospital. DIAGNOSIS: The patient showed leukopenia, lymphopenia, serum creatinine elevation with proteinuria and hematuria, decreased serum C3 level, and was positive for anti-double stranded DNA antibody, anti-nuclear antibody, and direct Coombs test. He was diagnosed with SLE. Renal biopsy was performed, and the patient was diagnosed with lupus nephritis (class IV-G(A/C) + V defined by the International Society of Nephrology/Renal Pathology Society classification). Computed tomography revealed acute interstitial pneumonitis, bronchoalveolar lavage fluid showed elevation of the lymphocyte fraction, and he was diagnosed with lupus pneumonitis. INTERVENTIONS: Prednisolone (50 mg/day) with intravenous cyclophosphamide (500 mg/body) were initiated. OUTCOMES: The patient showed a favorable response to these therapies. He was discharged from our hospital and received outpatient care with prednisolone slowly tapered off. He had cytomegalovirus and herpes zoster virus infections during treatment, which healed with antiviral therapy. REVIEW: We searched for the literature on sSLE, and selected 11 case reports and 2 population-based studies. The prevalence of SLE manifestations in sSLE patients were comparative to that of general SLE, particularly that of elderly-onset SLE. Our renal biopsy report and previous reports indicate that lupus nephritis of sSLE patients show as various histological patterns as those of general SLE patients. Among the twenty sSLE patients reported in the case articles, three patients developed lupus pneumonitis and two of them died of it. Moreover, two patients died of bacterial pneumonia, one developed aspergillus abscesses, one got pulmonary tuberculosis, and one developed lung cancer. CONCLUSION: Close attention is needed, particularly for respiratory system events and infectious diseases, when treating patients with silica-associated SLE using immunosuppressive therapies.

Circulating GPIHBP1 levels and microvascular complications in patients with type 2 diabetes: A cross-sectional study.

BACKGROUND: Glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 (GPIHBP1) plays a crucial role in lipolytic processing. Previous studies have shown that GPIHBP1 mutations cause severe hypertriglyceridemia and that serum GPIHBP1 levels are marginally higher in patients with coronary heart disease; however, the role of GPIHBP1 in type 2 diabetes mellitus (T2DM) remains unknown. OBJECTIVE: We investigated the association between circulating GPIHBP1 levels and the prevalence of microvascular complications in T2DM. METHODS: A total of 237 subjects with T2DM and 235 non-diabetic control subjects were enrolled in this study. Their serum GPIHBP1 levels were evaluated using ELISA assays. RESULTS: Circulating GPIHBP1 levels were higher in patients with T2DM (952.7 pg/mL [761.3-1234.6], p < 0.0001) than in non-diabetic subjects (700.6 [570.8-829.6]), but did not differ in T2DM patients with or without hypertriglyceridemia. Serum GPIHBP1 levels were significantly higher in patients with T2DM with diabetic retinopathy (DR), diabetic nephropathy (DN), and microvascular complications than in those without these complications. Multivariable logistic regression and receiver operating characteristic (ROC) curve analyses revealed that the presence of microvascular complications, but not macrovascular complications, was independently associated with serum GPIHBP1 levels, which could predict the presence of diabetic microvascular complications. CONCLUSIONS: Elevated GPIHBP1 levels are associated with microvascular complications in T2DM and may help to predict their progression.

Longitudinal observation of insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes mellitus: A report of two cases.

Immune checkpoint inhibitor-induced diabetes mellitus is a rare immune-related adverse event. This report illustrates clinical data and insulin secretory ability before and after the onset of immune checkpoint inhibitor-induced diabetes.

The effect of Humanitude care methodology on improving empathy: a six-year longitudinal study of medical students in Japan.

BACKGROUND: Empathy, which involves understanding another person's experiences and concerns, is an important component for developing physicians' overall competence. This longitudinal study was designed to test the hypothesis that medical students' empathy can be enhanced and sustained by Humanitude Care Methodology, which focuses on perception, emotion and speech. METHODS: This six-year longitudinal observational study examined 115 students who entered Okayama University Medical School in 2013. The study participants were exposed to two empathy-enhancing programs: (1) a communication skills training program (involving medical interviews) and (2) a Humanitude training program aimed at enhancing their empathy. They completed the Jefferson Scale of Empathy (JSE) seven times: when they entered medical school, before participation in the first program (medical interview), immediately after the first program, before the second program (Humanitude exercise), immediately after the second program, and in the 5th and 6th year (last year) of medical school. A total of 79 students (69% of the cohort) completed all seven test administrations of the JSE. RESULTS: The mean JSE scores improved significantly after participation in the medical interview program (p < 0.01) and the Humanitude training program (p = 0.001). However, neither program showed a sustained effect. CONCLUSIONS: The Humanitude training program as well as medical interview training program, had significant short-term positive effects for improving empathy among medical students. Additional reinforcements may be necessary for a long-term sustained effect.

Novel Urinary Glycan Biomarkers Predict Cardiovascular Events in Patients With Type 2 Diabetes: A Multicenter Prospective Study With 5-Year Follow Up (U-CARE Study 2).

Background: Although various biomarkers predict cardiovascular event (CVE) in patients with diabetes, the relationship of urinary glycan profile with CVE in patients with diabetes remains unclear. Methods: Among 680 patients with type 2 diabetes, we examined the baseline urinary glycan signals binding to 45 lectins with different specificities. Primary outcome was defined as CVE including cardiovascular disease, stroke, and peripheral arterial disease. Results: During approximately a 5-year follow-up period, 62 patients reached the endpoint. Cox proportional hazards analysis revealed that urinary glycan signals binding to two lectins were significantly associated with the outcome after adjustment for known indicators of CVE and for false discovery rate, as well as increased model fitness. Hazard ratios for these lectins (+1 SD for the glycan index) were UDA (recognizing glycan: mixture of Man5 to Man9): 1.78 (95% CI: 1.24-2.55, P = 0.002) and Calsepa [High-Man (Man2-6)]: 1.56 (1.19-2.04, P = 0.001). Common glycan binding to these lectins was high-mannose type of N-glycans. Moreover, adding glycan index for UDA to a model including known confounders improved the outcome prediction [Difference of Harrel's C-index: 0.028 (95% CI: 0.001-0.055, P = 0.044), net reclassification improvement at 5-year risk increased by 0.368 (0.045-0.692, P = 0.026), and the Akaike information criterion and Bayesian information criterion decreased from 725.7 to 716.5, and 761.8 to 757.2, respectively]. Conclusion: The urinary excretion of high-mannose glycan may be a valuable biomarker for improving prediction of CVE in patients with type 2 diabetes, and provides the rationale to explore the mechanism underlying abnormal N-glycosylation occurring in patients with diabetes at higher risk of CVE. Trial Registration: This study was registered with the University Hospital Medical Information Network on June 26, 2012 (Clinical trial number: UMIN000011525, URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000013482).

Effect of uremic toxins on hippocampal cell damage: analysis in vitro and in rat model of chronic kidney disease.

One third of the patients with chronic kidney disease (CKD) develop cognitive impairment, which is also an independent risk factor for mortality. However, the concise mechanism of cerebro-renal interaction has not been clarified. The present study examines the effects of uremic toxins on neuronal cells and analyzes the pathological condition of the brain using mouse hippocampal neuronal HT-22 cells and adenine-induced CKD model rats. Among the uremic toxins analyzed, indoxyl sulfate, indole, 3-indoleacetate, and methylglyoxal significantly decreased viability and glutathione level in HT-22 cells. The mixture of these uremic toxins also decreased viability and glutathione level at a lower dose. Adenine-induced CKD rat showed marked renal damage, increased urinary oxidative stress markers, and increased numbers of pyknotic neuronal cells in hippocampus. CKD rats with damaged hippocampus demonstrated poor learning process when tested using the Morris water maze test. Our results suggest that uremic toxins have a toxic effect on hippocampal neuronal cells and uremic CKD rats shows pyknosis in hippocampus.

Effect of an auxin biosynthesis inhibitor, p-phenoxyphenyl boronic acid, on auxin biosynthesis and development in rice.

p-Phenoxyphenyl boronic acid (PPBo) is a specific inhibitor of auxin biosynthesis in Arabidopsis. We examined the inhibitory activity of PPBo in rice. The activity of OsYUCCA, a key enzyme for auxin biosynthesis, was inhibited by PPBo in vitro. The endogenous indole-3-acetic acid (IAA) level and the expression levels of auxin-response genes were significantly reduced in PPBo-treated rice seedlings, which showed typical auxin-deficiency phenotypes. Seminal root growth was promoted by 1 µM PPBo, which was reversed by co-treatment of IAA and PPBo. By contrast, the inhibition of root growth by 10 µM PPBo was not recovered by IAA. The root meristem morphology and cell division were restored by IAA at 60 µM, but that concentration may be too high to support root growth. In conclusion, PPBo is an inhibitor of auxin biosynthesis that targets YUCCA in rice.

The hypoglycemia-prevention effect of sensor-augmented pump therapy with predictive low glucose management in Japanese patients with type 1 diabetes mellitus: a short-term study.

AIMS/INTRODUCTION: The predictive low glucose management (PLGM) system was introduced in March 2018 in Japan. Although there are some reports demonstrating the benefit of PLGM in preventing hypoglycemia, no data are currently available in Japanese patients with type 1 diabetes mellitus (T1DM). The aim of the present study is to evaluate the effect of PLGM with sensor-augmented pump therapy in the prevention of hypoglycemia in Japanese patients. MATERIALS AND METHODS: We included 16 patients with T1DM who used the MiniMed®640G system after switching from the MiniMed®620G system. We retrospectively analysed the data of the continuous glucose monitoring system in 1 month after switching to MiniMed®640G. RESULTS: The area under the curve (AUC) of hypoglycemia of < 70 mg/dL was lowered from 0.42 ± 0.43 mg/dL day to 0.18 ± 0.18 mg/dL day (P = 0.012). Correspondingly, the duration of severe hypoglycemia (< 54 mg/dL) was reduced significantly from 15.3 ± 21.7 min/day to 4.8 ± 6.9 min/day (P = 0.019). The duration of hypoglycemia was reduced, but the reduction was not significant. Regarding the AUC for hyperglycemia > 180 mg/dL and the duration of hyperglycemia did not change. With the PLGM function, 79.3% of the predicted hypoglycemic events were avoided. CONCLUSIONS: The hypoglycemia avoidance rate was comparable to those in previous reports. In addition, we demonstrated that PLGM can markedly suppress severe hypoglycemia without deteriorating glycemic control in Japanese T1DM patients. It is necessary to further investigate the effective use of the PLGM feature such as establishing a lower limit and the timing of resumption.

A Patient with Type 3 Autoimmune Polyglandular Syndrome who Developed Systemic Lupus Erythematosus 8 years after the Diagnosis of Autoimmune Hepatitis.

Eight years prior to her present admission, a 61-year-old Japanese woman was diagnosed with autoimmune hepatitis, slowly progressive insulin-dependent diabetes mellitus, and chronic thyroiditis; she had been treated with oral prednisolone (PSL). After she suddenly discontinued PSL, she newly developed systemic lupus erythematosus. A combination therapy of oral PSL and intravenous cyclophosphamide resulted in remission. She was finally diagnosed with autoimmune polyglandular syndrome (APS) type 3 (3A ,3B, 3D), complicated with four different autoimmune diseases. Since patients with type 3 APS may present many manifestations over a long period of time, they should be carefully monitored.

Risk Factors for the Requirement of Antenatal Insulin Treatment in Gestational Diabetes Mellitus.

Poor maternal glycemic control increases maternal and fetal risk for adverse outcomes, and strict management of gestational diabetes mellitus (GDM) is recommended to prevent neonatal and maternal complications. However, risk factors for the requirement of antenatal insulin treatment (AIT) are not well-investigated in the pregnant women with GDM. We enrolled 37 pregnant women with GDM and investigated the risk for AIT by comparing the patients with AIT (AIT group; n = 10) and without insulin therapy (Diet group; n = 27). The 1-h and 2-h plasma glucose levels and the number of abnormal values in 75 g OGTT were significantly higher in AIT group compared with Diet group. By logistic regression analysis, plasma glucose level at 1-h was significant predictor for AIT and the odds ratios were 1.115 (1.004-1.239) using forward selection method and 1.192 (1.006-1.413) using backward elimination method. There were no significant differences in obstetrical outcomes and neonatal complications. 1-h plasma glucose levels in 75 g OGTT are useful parameters in predicting the requirement for AIT in GDM. Both maternal and neonatal complications are comparable in GDM patients with and without insulin therapy.

Association of cystatin C with leptin and TNF-α in elderly Japanese women.

BACKGROUND AND OBJECTIVES: Determinants of cystatin C, a novel marker of mortality in the elderly, have not been extensively studied in Asian elderly population. METHODS AND STUDY DESIGN: Associations of cystatin C with anthropometric, cardiometabolic, hematological, nutritional variables and inflammatory markers were examined in 159 community-living elderly Japanese women whose BMI averaged 22.6±2.9 (SD) kg/m2. RESULTS: Serum creatinine and cystatin C averaged 0.73±0.16 mg/dL and 0.85±0.20 mg/L, respectively. Creatinine-based estimated glomerular filtration rate (standardized ß, -0.538, p<0.001), age (standardized ß, 0.274, p<0.001), serum leptin (standardized ß, 0.218, p<0.001) and tumour necrosis factor-α (TNF-α, standardized ß, 0.165, p=0.002) emerged as significant predictors of serum cystatin C independent of percentage body fat, homeostasis model assessment of insulin resistance, high-sensitivity C-reactive protein, systolic blood pressure and HDL cholesterol (cumulative R2=0.674). CONCLUSIONS: Elevated serum levels of leptin and TNF-α contributed to elevated cystatin C independent of kidney function, fat mass, insulin resistance and inflammation in community-living elderly women and may represent confounders of associations between cystatin C and mortality in this population.

Direct association of visit-to-visit HbA1c variation with annual decline in estimated glomerular filtration rate in patients with type 2 diabetes.

BACKGROUND/AIMS: This study examined associations of visit-to-visit variability of glycemic control with annual decline in estimated glomerular filtration rate (eGFR) in patients with type 2 diabetes attending an outpatient clinic. METHODS: Intrapersonal mean and coefficient of variation (CV) of 8-12 measurements of HbA1c and those of 4-6 measurements of fasting and post-breakfast plasma glucose (FPG and PPG, respectively) during the first 12 months after enrollment were calculated in a cohort of 168 patients with type 2 diabetes. Annual changes in eGFR were computed using 52 (median) creatinine measurements obtained over a median follow-up of 6.0 years. Multivariate linear regressions assessed the independent correlates of changes in eGFR. RESULTS: CV-HbA1c (standardized ß、-0.257、p = 0.004) were significantly and log urine albumin/creatinine ratio (standardized ß、-0.155、p = 0.085) and smoking (standardized ß、-0.186、p = 0.062) tended to be associated with annual eGFR decline independently of mean HbA1c, age, sex, BMI, waist circumference, diabetes duration and therapy, means and CVs of FPG, PPG and systolic blood pressure, baseline eGFR, and uses of anti-hypertensive and lipid-lowering medications. Association between HbA1c variability and renal function decline was stronger in patients with albumin/creatinine ratio ≧ 30 mg/g than in those with normoalbuminuria (r = -0.400, p = 0.003 and r = -0.169, p = 0.07, respectively). CONCLUSIONS: Consistency of glycemic control is important to preserve kidney function in type 2 diabetic patients, in particular, in those with nephropathy.

Associations of decreased serum transthyretin with elevated high-sensitivity CRP, serum copper and decreased hemoglobin in ambulatory elderly women.

BACKGROUND: Transthyretin (TTR), a sensitive indicator of malnutrition and inflammation, has been shown to be associated with mortality in elderly population. METHODS: We examined relationships between serum TTR and a range of risk factors for mortality in 185 free-living elderly women. Blood was drawn between breakfast and lunch. RESULTS: TTR was correlated negatively with age (r=-0.30, p<0.001). After controlling for age, TTR was negatively associated with log high-sensitivity CRP (hsCRP) and serum copper. It was positively associated with albumin, serum iron and hemoglobin. In addition, TTR was positively correlated with systolic and diastolic blood pressure and postprandial triglyceride (TG). In multiple regression analysis for TTR as a dependent variable, hemoglobin (standardized ß, 0.244), serum copper (standardized ß, -0.134), postprandial TG (standardized ß, 0.223) and log hsCRP (standardized ß, -0.190) emerged as determinants of TTR independently of age, albumin, serum iron, systolic and diastolic blood pressure, and explained 22.8% of TTR variability. CONCLUSIONS: Subclinical low-grade inflammation, elevated serum copper and decreased hemoglobin were associated with decreased serum TTR in community-living elderly Japanese women and may represent important confounders of the relationship between low TTR and mortality in the elderly. The positive association of TTR with postprandial TG warrants further investigation.

Serum copper, zinc and risk factors for cardiovascular disease in community-living Japanese elderly women.

BACKGROUND: Associations of copper (Cu) and zinc (Zn) serum levels with risk factors for cardiovascular disease (CVD) have not been extensively studied in elderly Asian people. METHODS: Relationships to CVD risk factors were examined in 202 freely-living elderly Japanese women. RESULTS: By univariate analysis, log high-sensitivity C-reactive protein (hsCRP) and non-HDL cholesterol were associated with serum Cu concentrations. An independent predictor of Cu was log hsCRP. Serum Zn concentrations decreased with age. After adjustment for age, serum albumin, HDL cholesterol and red blood cell (RBC) were positively and serum insulin and log hsCRP were inversely associated with serum Zn. In stepwise multiple regression analysis (model 1), serum albumin and HDL cholesterol were associated with serum Zn. In analysis excluding albumin from model 1 (model 2), independent determinants were log hsCRP (inverse) and the total number of RBC. In analysis including serum creatinine in model 2, creatinine has emerged as a determinant in addition to log hsCRP and RBC number. In analysis including estimated glomerular filtration rate (eGFR) instead of creatinine and excluding age in model 2, eGFR has emerged as a determinant of serum Zn in addition to log hsCRP and RBC number. CONCLUSIONS: Systemic low-grade inflammation may contribute to elevated serum Cu and decreased serum Zn concentrations in the elderly, and may represent an important confounder of the relationship between the serum trace elements and mortality in this population.

Association of adiponectin with serum preheparin lipoprotein lipase mass in women independent of fat mass and distribution, insulin resistance, and inflammation.

UNLABELLED: Abstract Background: Substantially increased lipoprotein lipase (LPL) activity was reported in mice overexpressing adiponectin. METHODS: Associations of serum adiponectin with serum preheparin LPL mass (serum LPL), fat mass, and fat distribution and markers of insulin resistance and inflammation were examined in 311 young and 148 middle-aged women. RESULTS: In young women, serum adiponectin was positively associated with high-density lipoprotein cholesterol (HDL-C) and serum LPL and inversely with body mass index (BMI), abdominal girth, trunk fat mass, trunk/lower-body fat ratio, serum leptin, and log high-sensitivity C-reactive protein. These associations were confirmed in middle-aged women. Adiponectin showed positive association with the Matsuda insulin sensitivity index and inverse associations with homeostasis model assessment of insulin resistance, serum triglycerides, leukocyte count, interleukin-6, and plasminogen activator inhibitor-1 in middle-aged women but not in young women. Multivariate analysis revealed that serum LPL and trunk/lower-body fat ratio were significant determinants of adiponectin, not only in young women but also in middle-aged women. These associations were independent of markers of inflammation and insulin sensitivity/resistance. CONCLUSIONS: LPL mass in preheparin serum was associated with adiponectin levels independently of fat mass and distribution, systemic inflammation, and insulin resistance in healthy women. Therefore, LPL may represent a link between low adiponectin and dyslipidemia found in metabolic syndrome and type 2 diabetes mellitus.