Effect of statin treatment on mortality in elderly patients with type 2 diabetes mellitus patients: a retrospective cohort study.

BACKGROUND: The effects of statins on the reduction of mortality in individuals aged 75 years or older remain controversial. We conducted this study to investigate whether there is an association between statin therapy and mortality in patients with type 2 diabetes mellitus (T2DM) who are over the age of 75 years. METHODS: The present study used data from the Staged Diabetes Targeting Management Study, which began in 2005. A total of 518 T2DM patients older than 75 years were included. Cox regression analyses were used to evaluate the association between statins and specific causes of death in patients with T2DM. RESULTS: After a follow-up period of 6.09 years (interquartile range 3.94-8.81 years), 111 out of 518 patients died. The results of Cox regression analyses showed that there was no significant association between statin use and all-cause mortality (HR 0.75; 95% CI 0.47, 1.19) after adjustment for all potential confounders. Subgroup analysis indicated that statins had no association with the risk of all-cause mortality or deaths caused by ischemic cardiovascular diseases in T2DM patients with or without coronary heart disease. CONCLUSIONS: Our study found no significant association between all-cause mortality and statin use in T2DM patients over the age of 75 years. More evidence is needed to support the use of statins in the elderly T2DM patients.

Association between serum uric acid/HDL-cholesterol ratio and chronic kidney disease: a cross-sectional study based on a health check-up population.

OBJECTIVE: Evidence suggests that both serum uric acid (SUA) and high-density lipoprotein cholesterol (HDL-C) are risk factors for chronic kidney disease (CKD). The SUA-to-HDL-C ratio (UHR) has recently attracted attention as a new biomarker to evaluate the role between inflammatory and anti-inflammatory substances. Thus, we explored the association between UHR and CKD in a large Chinese population. DESIGN: A cross-sectional study. SETTING: Annual health check-up population in Nanjing. PARTICIPANTS: 19 458 individuals who underwent an annual health check-up in 2019 were included in our study. MAIN OUTCOME MEASURE: CKD was diagnosed according to an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. RESULTS: Correlation analysis showed that UHR was negatively associated with eGFR after adjusting for confounding factors (r=-0.34). In addition, participants in the highest quartile of UHR had a higher risk of CKD than those in the lowest quartiles (OR=9.28, p<0.001). CONCLUSION: We found that high UHR values were positively associated with CKD risk in health check-up population. An increased UHR may be a useful measure by which to assess CKD risk in the preclinical stage.

Total extract of Abelmoschus manihot L. alleviates uric acid-induced renal tubular epithelial injury via inhibition of caspase-8/caspase-3/NLRP3/GSDME signaling.

Purpose: The incidence of uric acid (UA)-induced kidney injury is increasing owing to the high incidence of hyperuricemia in recent years. The flower of Abelmoschus manihot (Linneus) Medik is a traditional Chinese medicinal herb widely used in the treatment of some kidney diseases. In our previous study, we reported that the total extract of A. manihot L. flower (TEA) attenuated adriamycin-induced renal tubular cell injury. In this study, we aimed to evaluate the role of TEA in UA-induced tubular cell injury. Methods: Normal rat proximal epithelial NRK-52E cells were incubated with UA to mimic hyperuricemia conditions. The role of TEA in the renal tubular cells was also assessed. The cellular morphology was observed using phase-contrast microscopy, and cell viability was analyzed using the Cell Counting kit-8. Living and dead cells were stained using a Calcein-AM/PI double stain kit. The release of lactate dehydrogenase (LDH) was analyzed by LDH cytotoxicity Assay Kit. The expression of target proteins was analyzed using western blot analysis. Results: UA triggered NRK-52E cell injury, as evidenced by morphological changes, detachment of cells from the bottom, cell swelling, large bubbles blowing from cell membrane and loss of cell viability. UA increased release of LDH. UA induced the expression of p-ERK1/2 and the subsequent activation of caspase-8, caspase-3, and NLRP3 inflammasomes. Pyroptosis was elicited by UA after gasdermin E N-terminal (GSDME-NT) was cleaved from gasdermin E (GSDME). Z-DEVD-FMK, a caspase-3 inhibitor, suppressed the expression of both NLRP3 and GSDME-NT, but not that of caspase-8. INF39, an NLRP3 inhibitor, altered the expression of GSDME-NT expression, but not that caspase-3 and caspase-8. TEA alleviated UA-induced cell injury by suppressing ERK1/2/caspase-8/caspase-3/NLRP3/GSDME signaling. Conclusion: GSDME-mediated pyroptosis was involved in UA-induced renal tubular cell injury. This is the first study to report that TEA protects renal tubular epithelial cells against UA by inhibiting the ERK/1/2/caspase-8/caspase-3/NLRP3/GSDME pathway.

The association between the serum uric acid to creatinine ratio and all-cause mortality in elderly hemodialysis patients.

BACKGROUND: Elderly hemodialysis patients have a higher rate of mortality than nonelderly hemodialysis patients. Recent studies shown that the serum uric acid to creatinine ratio (SUA/Scr) was associated with all-cause mortality in general adults. The purpose of the present study was to investigate the association between the SUA/Scr and all-cause and cardiovascular disease mortality among elderly hemodialysis patients. METHODS: A total of 222 patients (≥ 60 years) who received hemodialysis more than 8 h per week at Taizhou Second People's Hospital for at least 3 months were enrolled in the present study from January 2015 to December 2019. Clinical characteristics including age, sex and height et. al, were obtained from the hemodialysis database. The laboratory data, including albumin (ALB), total cholesterol (TC), serum uric acid (SUA), serum creatinine (Scr) and so on, were collected before hemodialysis and analyzed by automatic biochemical analyzer. Survival information was recorded during the follow-up period. Multiple Cox regression was carried out to analyze the association between SUA/Scr and all-cause mortality. The survival rate of each group was calculated by the Kaplan-Meier method, and the ratio of survival curves was analyzed by the log-rank test. The contribution of SUA/Scr for predicting all-cause mortality risk was evaluated by net reclassification improvement (NRI). RESULTS: During the 19-month observation period, 78 patients died. Individuals in the nonsurviving group had significantly older ages (P < 0.001), body mass index (BMI) (P = 0.004), serum creatinine (P = 0.005) and prealbumin (P = 0.006) than surviving patients. After adjusting for age, sex, BMI, prealbumin, dialysis vintage, dialysis frequency, single-pool Kt/V (spKt/V), DM, hypertension and comorbidities, a higher ratio of SUA/Scr was independently associated with a higher risk of all-cause mortality (HR: 1.292; 95% CI: 1.013-1.648; P = 0.039). The predict value on all-cause mortality of SUA/Scr was superior to SUA (additive NRI = 0.214, P = 0.015) and Scr (additive NRI = 0.476, P < 0.001) among elderly hemodialysis patients. CONCLUSION: The serum uric acid to creatinine ratio is strongly associated with all-cause mortality in elderly hemodialysis patients which is more predictive than SUA or Scr alone.

Time trend of cardiometabolic risk factors over a 10-year period in the office-working population in China.

OBJECTIVES: Recent dramatic increases in cardiovascular disease mortality in China can be mostly explained by adverse changes in hypertension, dyslipidaemia, diabetes and obesity, known as cardiometabolic risk factors. Our study aimed to assess the trend of these four signatures by a 10-year lag in Nanjing, China. METHODS: 8017 subjects attended the routine health examination in 2008, and 9379 subjects in 2017, from multiple work units of Nanjing, were included in the present study. The prevalence and trend of four cardiometabolic risk factors: hypertension, dyslipidaemia, diabetes and obesity were analysed. RESULTS: From 2008 to 2017, the prevalence of hypertension declined, while the prevalence of dyslipidaemia, diabetes and obesity increased. Besides, the population in 2008 and 2017 had an average of 0.66 and 0.78 risk factors, respectively. CONCLUSION: Cardiometabolic risk factors are common for the staff in administrative agencies and institutions of Nanjing, China. Effective screening and interventions against these risk factors should be adopted in high-risk populations such as the office-working population in China.

Association of Thyroid Function With the Estimated Glomerular Filtration Rate in a Large Chinese Euthyroid Population.

BACKGROUND/AIMS: We aimed to explore whether thyroid function within a normal range is associated with the estimated glomerular filtration rate (eGFR) and the incidence of chronic kidney disease (CKD) in a large Chinese population. METHODS: We conducted a cross-sectional study that included 10,859 euthyroid individuals who underwent an annual regular health checkup in Jiangsu Province Official Hospital between August 2012 and August 2013. We measured the thyroid-stimulating hormone (TSH), free triiodothyronine (FT3) and free thyroxine (FT4) levels using a Roche modular analytics E170 and then calculated the eGFR using the Chinese modified Modification of Diet in Renal Disease (CMDRD) equation. RESULTS: In multiple linear regression models, TSH was negatively associated with eGFR after adjusting for confounding factors (ß = -0.072, P = 1.994×10-22). The significance remained in both males and females. No significant association was observed between FT4 and eGFR. In the logistic regression model, we did not observe significant associations of TSH or FT3 with CKD. Participants in the highest quartile of FT4 versus the lowest quartile (reference) had an increased risk of CKD (OR = 1.763, P = 0.012). The risk of CKD was more pronounced in females with the highest quartile of FT4 (OR = 2.424, P = 0.029). CONCLUSION: Our findings suggest that TSH is associated with eGFR in euthyroid individuals and that higher FT4 is associated with an increased risk of CKD. More cohort studies are warranted to confirm whether the association is causal.

Serum uric acid to creatinine ratio correlates with ß-cell function in type 2 diabetes.

BACKGROUND: The correlation between serum uric acid (SUA) and ß-cell function remains controversial. The present study aims to use a new index, renal function-normalized SUA, to observe its correlation with ß-cell function in patients with type 2 diabetes (T2DM). METHODS: A total of 713 patients with T2DM received standard 75-g oral glucose tolerance and insulin release test. Renal function-normalized SUA was calculated using SUA/creatinine and ß-cell function was assessed by HOMA-B. Binary logistic regression analysis was used to estimate the association between SUA/creatinine and ß-cell function. RESULTS: There are positive correlations between SUA/creatinine and HOMA-B (r = 0.143, P < 0.001), as well as other indexes of ß-cell function including modified ß-cell function index (r = 0.104, P = 0.007), InsAUC30 (r = 0.100, P = 0.008), and InsAUC120 (r = 0.124, P = 0.001). SUA/creatinine also positively correlates with insulin resistance (HOMA-IR: r = 0.161, P < 0.001). Moreover, multivariate analysis revealed that SUA/creatinine was significantly associated with preserved ß-cell function, independently of potential confounders including sex, BMI, and renal function. CONCLUSIONS: SUA to creatinine ratio correlates with ß-cell function in T2DM patients.

PFOA is associated with diabetes and metabolic alteration in US men: National Health and Nutrition Examination Survey 2003-2012.

Exposure to perfluoroalkyl substances (PFAS) is associated with a range of adverse health effects. However, it remains unclear whether PFAS at environmentally relevant exposure levels are related to diabetes and metabolite concentrations in adults. Using cross-sectional data from 7904 adults (age≥20years) in the 2003-2012 National Health and Nutrition Examination Survey (NHANES), we examined the association of PFAS with the prevalence of diabetes and metabolite concentrations. A multivariate logistic regression was applied to investigate the associations of diabetes prevalence with serum perfluorooctanoate (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonate (PFHxS) and perfluorononanoate (PFNA) levels. A multivariate generalised linear regression was further performed to investigate the associations between PFAS exposure and some metabolites. We identified a strong positive association between serum PFOA and diabetes prevalence in men with an adjusted model (OR: 2.66, 95% CI: 1.63-4.35; P for trend=0.001). No significant association between serum PFOA and diabetes prevalence was observed in women (OR: 1.47, 95% CI: 0.88-2.46; P for trend=0.737). Furthermore, diabetes was not related to PFOS, PFHxS and PFNA, regardless of gender. In the gender-stratified generalised linear models, men and women with the highest PFOA levels demonstrated a 1.43% (95% CI: 0.62%-2.34%) and a 1.07% (95% CI: 0.27%-1.97%) greater increase in serum total cholesterol (P for trend=0.006 and 0.001) compared to those with the lowest PFOA levels. There were no significant associations between serum PFOA and other metabolites. These results provide epidemiological evidence that environment-related levels of serum PFOA may be positively associated with the prevalence of diabetes in men and with total cholesterol in adults. Further clinical and animal studies are urgently needed to elucidate putative causal relationships and shed light on the potential mode of action involved.

Effects of Medical Insurance on the Health Status and Life Satisfaction of the Elderly.

BACKGROUND: Population aging has become increasingly serious in China. The demand for medical insurance of the elderly is increasing, and their health status and life satisfaction are becoming significant issues. This study investigates the effects of medical insurance on the health status and life satisfaction of the elderly. METHODS: The national baseline survey data of the China Health and Retirement Longitudinal Survey in 2013 were adopted. The Ordered Probit Model was established. The effects of the medical insurance for urban employees, medical insurance for urban residents, and new rural cooperative medical insurance on the health status and life satisfaction of the elderly were investigated. RESULTS: Medical insurance could facilitate the improvement of the health status and life satisfaction of the elderly. Accordingly, the health status and life satisfaction of the elderly who have medical insurance for urban residents improved significantly. The regression coefficients were 0.348 and 0.307. The corresponding regression coefficients of the medical insurance for urban employees were 0.189 and 0.236. The regression coefficients of the new rural cooperative medical insurance were 0.170 and 0.188. CONCLUSION: Medical insurance can significantly improve the health status and life satisfaction of the elderly. This development is of immense significance for the formulation of equal medical security.

Rhein Inhibits Autophagy in Rat Renal Tubular Cells by Regulation of AMPK/mTOR Signaling.

Rhubarb and its bioactive component rhein are frequently used for the treatment of chronic kidney diseases (CKD) in eastern Asia countries. However, the potential therapeutic mechanism remains unclear. Autophagy plays an important role in CKD. However, there were some important related issues that remained unresolved in the role of autophagy in CKD and treatment by rhubarb and rhein. We designed a number of experiments to examine whether rhubarb may reduce renal fibrosis and autophagy in rats with adenine (Ade)-induced renal tubular injury, and whether rhein could affect autophagic pathways in rat renal tubular cells. We found that, autophagic activation accompanied with renal fibrosis in rats with Ade-induced renal tubular injury, and both autophagy and renal fibrosis were attenuated by rhubarb. In addition, we observed that rhein could inhibit autophagy through regulating the key molecules in the AMPK-dependent mTOR signaling pathways, as well as the Erk and p38 MAPKs signaling pathways. These findings may partly explain the therapeutic mechanisms of rhubarb and rhein in treating CKD patients in clinic, and further suggest that targeting autophagy and related signaling pathways may provide new strategies for the treatment of renal fibrosis in CKD.

Serum uric acid to creatinine ratio: A predictor of incident chronic kidney disease in type 2 diabetes mellitus patients with preserved kidney function.

BACKGROUND: Serum uric acid has shown to be a predictor of renal disease progression in most but not all studies. This study aims to test whether renal function-normalized serum uric acid is superior to serum uric acid as the predictor of incident chronic kidney disease in type 2 diabetes mellitus patients. METHODS: In this study, 1339 type 2 diabetes mellitus patients with estimated glomerular filtration rate ⩾60 mL/min/1.73 m2 and normouricemia were included. Renal function-normalized serum uric acid was calculated using serum uric acid/creatinine. Cox regression analysis was used to estimate the association between serum uric acid, renal function-normalized serum uric acid and incident chronic kidney disease. RESULTS: In total, 74 (5.53%) patients developed to chronic kidney disease 3 or greater during a median follow-up of 4 years, with older ages, longer diabetes duration and lower estimated glomerular filtration rate at baseline. The decline rate of estimated glomerular filtration rate was positively correlated with serum uric acid/creatinine ( r = 0.219, p < 0.001), but not serum uric acid ( r = 0.005, p = 0.858). Moreover, multivariate analysis revealed that serum uric acid was not an independent risk factor for incident chronic kidney disease ( p = 0.055), whereas serum uric acid to creatinine ratio was significantly associated with incident chronic kidney disease independently of potential confounders including baseline estimated glomerular filtration rate. CONCLUSION: serum uric acid to creatinine ratio might be a better predictor of incident chronic kidney disease in type 2 diabetes mellitus patients.

Evaluation of glycemic control in patients with type 2 diabetes mellitus in Chinese communities: a cross-sectional study.

This study aimed to evaluate the glycemic levels in Chinese patients with type 2 diabetes mellitus (T2DM) and to explore the factors related to the results of glycemic control. A total of 2454 T2DM patients from 11 communities were examined for glycosylated hemoglobin levels and glycemic control options. Potential factors related to the results of glycemic control were analyzed using logistic regression. Of all the patients, 55.3 % achieved the glycemic control target of HbA1c < 7 %. Multivariate analysis showed that male sex (OR 1.345, 95 % CI 1.022-1.769; P = 0.034), higher levels of fasting blood glucose (OR 1.954, 95 % CI 1.778-2.147; P < 0.001), and low-density lipoprotein cholesterol (OR 1.181, 95 % CI 1.020-1.367; P = 0.026) were significantly associated with poor glycemic control. The complexity of antidiabetics was also associated with poor glycemic control (P < 0.05). Compared to diet and exercise, insulin injection was most strongly associated with poor glycemic control (OR 6.210, 95 % CI 4.054-9.514; P < 0.001). Male patients with higher levels of total cholesterol, lower levels of high-density lipoprotein cholesterol, or longer diabetic durations showed poor glycemic control, which was not found in female patients. Glycemic control was not satisfactory in T2DM patients of Nanjing communities. Various factors are associated with poor results of glycemic control.

Huaiqihuang Granules () reduce proteinuria by enhancing nephrin expression and regulating necrosis factor κB signaling pathway in adriamycin-induced nephropathy.

OBJECTIVE: To investigate the effects of Huaiqihuang Granules (, HQH), a mixture of Chinese herbs including Trametes robiniophila Murr, Fructus Lycii and Polygonatum sibiricum, on adriamycininduced nephropathy (ADRN) in rats and its underlying mechanisms. METHODS: Rats with ADRN were divided into four groups: the sham group, the model group (distilled water), the low-dose HQH-treated (2 g/kg) group, and the high-dose HQH-treated (4 g/kg) group. Body weight and 24-h urinary protein (Upro) were checked every week. After 5-week intervention, at the end of the study, the rats were sacrificed and blood samples were collected for examination of biochemical parameters, including glomerular morphological makers, podocyte shape, cellular apoptosis, expressions of nephrin, inflammatory and apoptosis markers. RESULTS: HQH ameliorated the rat's general status, proteinuria, renal morphological appearance and glomerulosclerosis. The decreased expression of nephrin in ADRN rats was increased by HQH, as well as the impaired podocyte foot process fusion. Cytosolic levels of p65 and inhibitor of nuclear factor κBα (IκBα) were decreased in ADRN rats, and recovered by the treatment of HQH. Consistently, the induced expression of tumor necrosis factor α (TNF-α), phosphorylated nuclear factor κB p65 (p-NFκB p65) and IκBα in ADRN were markedly suppressed by HQH. In addition, induction of Bax, cleaved caspase-3 and cytochrome C in ADRN rats were suppressed by HQH, indicating the amelioration of apoptosis. CONCLUSION: HQH could ameliorate renal impairments in ADRN rats by increasing nephrin expression, inhibiting NF-κB signaling pathway via the down-regulation of p-NF-κB p65 and p-IκBα, and suppression of glomerular and tubular apoptosis.

Lack of association between anemia and renal disease progression in Chinese patients with type 2 diabetes.

AIMS/INTRODUCTION: Anemia has a close interaction with renal dysfunction in diabetes patients. More proof is still awaited on the relationship between anemia and the progression of renal disease in this population. MATERIALS AND METHODS: In the present longitudinal study, 1,645 Chinese type 2 diabetes patients without end-stage renal disease were included in the analysis in Nanjing, China, during January 2006 and December 2012. All patients were managed by staged diabetes management protocol, and clinical parameters were collected at each visit. The end-point of progression of renal disease was evaluated during the follow up. Cox regression analysis was used to estimate the risk of anemia on renal disease progression. RESULTS: On recruitment, 350 (21.3%) patients had anemia, which was more common among those with older ages, longer diabetes duration, lower estimated glomerular filtration rate or more albuminura. On median follow up of 49 months (range 28-62 months), 37 patients (2.2%) developed the defined renal end-point. Compared with those without anemia, patients with anemia had a higher risk of renal disease progression. However, multivariate analysis showed that anemia lost its statistical significance once estimated glomerular filtration rate was added into the model. Although the incidence of renal disease progression markedly increased by anemia status in patients of estimated glomerular filtration rate <60 mL/min/1.73 m(2), anemia was still not an independent risk factor for renal disease progression in this subgroup. CONCLUSIONS: Anemia was a common finding in Chinese type 2 diabetes patients. Anemia was a risk factor for renal disease progression, but lost its significance once baseline renal function was adjusted.

Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro by activating autophagy.

AIM: A previous report shows that emodin extracted from the Chinese herbs rhubarb and giant knotweed rhizome can ameliorate the anticancer drug cisplatin-induced injury of HEK293 cells. In this study, we investigated whether and how emodin could protect renal tubular epithelial cells against cisplatin-induced nephrotoxicity in vitro. METHODS: The viability and apoptosis of normal rat renal tubular epithelial cells (NRK-52E) were detected using formazan assay and flow cytometry analysis, respectively. The expression levels of cleaved caspase-3, autophagy maker LC3 I/II, and AMPK/mTOR signaling pathway-related proteins were measured with Western blot analysis. The changes of morphology and RFP-LC3 fluorescence were observed under microscopy. RESULTS: Cisplatin (10-50 µmol/L) dose-dependently induced cell damage and apoptosis in NRK-52E cells, whereas emodin (10 and 100 µmol/L) significantly ameliorated cisplatin-induced cell damage, apoptosis and caspase-3 cleavage. Emodin dose-dependently increased LC3-II levels and induced RFP-LC3-containing punctate structures in NRK-52E cells. Furthermore, the protective effects of emodin were abolished by bafilomycin A1 (10 nmol/L), and mimicked by rapamycin (100 nmol/L). Moreover, emodin increased the phosphorylation of AMPK and suppressed the phosphorylation of mTOR. The AMPK inhibitor compound C (10 µmol/L) not only abolished emodin-induced autophagy activation, but also emodin-induced anti-apoptotic effects. CONCLUSION: Emodin ameliorates cisplatin-induced apoptosis of rat renal tubular cells in vitro through modulating the AMPK/mTOR signaling pathways and activating autophagy. Emodin may have therapeutic potential for the prevention of cisplatin-induced nephrotoxicity.

[Molecular mechanism of emodin on inhibiting autophagy induced by HBSS in renal tubular cells].

OBJECTIVE: To explore the regulative effects and possible mechanisms of emodin on autophagy induced by starvation in rat's renal tubular epithelial cells (NRK-52E). METHOD: Firstly, Hank's balanced salt solution (HBSS) was used to induce starvation and the protein expression of microtubule-associated protein 1 light chain 3 (LC3) I/II, an autophagic marker of mammalian congener, was detected by Western blot with or without the treatment of emodin. Secondly, the changes of red fluorescent protein-microtubule associated protein light chain3 (RFP-LC3) fluorescent particles, treated by HBSS (1 mL) and bafilomycin A1 (10 nmol x L(-1)) with or without emodin, were observed through fluorescence microscopy in NRK-52E cells transient transfected by RFP-LC3 plasmid. With the intervention of mammalian target of rapamycin mTOR inhibitor rapamycin (100 nmol x L(-1)) , the effect of blocking mTOR signaling pathway on autophagic inhibition of emodin was observed. Finally, the effect of mTOR signaling pathway on autophagic inhibition of emodin was further evaluated through the over-expression of endogenous mTOR inhibitory protein DEP domain-containing mTOR-interacting protein-(DEPTOR). RESULT: HBSS hunger could induce high protein expression of LC3 II in NRK-52E cells, and the intervention of emodin could reverse the unregulated protein expression of LC3 II induced by HBSS. The number of RFP-LC3 fluorescent particles was increased after the co-treatment of HBSS and bafilomycin A1, and this increase was inhibited by emodin. After the co-treatment of rapamycin, emodin and HBSS, the LC3 II protein expression restored in NRK-52E cells, compared with the treatment of HBSS. Over-expression of DEPTOR could also block the inhibitive effect of emodin on LC3 II protein expression. CONCLUSION: Emodin could inhibit HBSS-induced LC3 II protein expression and the activation of autophagy in NRK-52E cells, and the effect of blocking autophagy may be mediated through mTOR signaling pathway.

Anthropometric parameters and their associations with cardio-metabolic risk in Chinese working population.

BACKGROUND: There remains controversy regarding which of the anthropometric indicators best defines obesity. In this study, we compared the efficacy of using body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) in the diagnosis of obesity and assessed their associations with diabetes, hypertension, and dyslipidemia in an urban working population in China. METHODS: Anthropometric measurements, blood pressure, plasma lipids, fasting and 2-hour plasma glucose (PG) levels by a 75 gram oral glucose tolerance test (OGTT) were obtained from 2603 working Chinese who had no history of cardiovascular diseases or diabetes. Cardio-metabolic risk factors including high blood pressure, dyslipidemia, and glucose intolerance were evaluated. The diagnoses of overweight and obesity were based on the WHO definitions with BMI for general obesity and WC and WHR for central obesity. RESULTS: Based on BMI, WC and WHR, there were 31.3%, 16.6%, 35.2% of the studied subjects, respectively, being overweight and 2.0%, 5.6%, 9.2% being obese. Among women but not men, more overweight and obese subjects were diagnosed using WHR and WC. The number of cardio-metabolic risks was higher by WC criterion than BMI and WHR in the whole group (p <0.05) and female subjects (p <0.01). Comparing the three anthropometric indexes predicting hypertension, hyperglycemia, dyslipidemia and multiple cardio-metabolic risks, for women, it was WC having the largest areas under ROC curves (0.759, 0.746, 0.701 and 0.773 respectively); while in men, it was WC for hypertension, WHR for hyperglycemia, BMI for dyslipidemia and WC for multiple cardio-metabolic risks (areas under ROC curves were 0.658, 0.686, 0.618 and 0.695 respectively). CONCLUSIONS: Among Chinese working population, the need of lower cutoff values to define overweight and obesity were observed. Central obesity indicator (WC) is the preferred measure to predict the presence of cardio-metabolic risk in Chinese female subjects.

[Clinical implication of urinary protein markers in diabetic nephropathy and interventional effects of Chinese herbal medicine].

In clinic, some urinary protein makers can dynamically and noninvasively reflect the degree of renal tubular injury in patients with diabetic nephropathy (DN). These urinary biomarkers of tubular damage are broadly divided into two categories. One is newfound, including kidney injury molecule-1 (Kim-1), neutrophil getatinase-associated lipocalin (NGAL), liver-type fatty acid-binding protein (L-FABP) and cystatin C (CysC); the other one is classical, including beta2 microglobulin (beta2-MG), retinal binding protein (RBP) and N-acetyl-beta-D-glucosaminidase (NAG). It is reported that, the increases in urinary protein markers are not only closely related to the damage of tubular epithelial cells in DN patients, but also can be ameliorated by the treatment with Chinese herbal compound preparations or Chinese herbal medicine. Recently, although urinary proteomics are used in the protein separation and identification, the traditional associated detection of urinary protein markers is more practical in clinic. At present, it is possible that the associated detection of urinary biomarkers of glomerular and tubular damages may be a feasible measure to reveal the clinical significance of urinary protein markers in DN patients and the interventional effects of Chinese herbal medicine.

[Molecular mechanism of rhein on inhibiting autophagic protein expression in renal tubular epithelial cells via regulating mTOR signaling pathway activation].

OBJECTIVE: To explore the effects and molecular mechanisms of rhein on reducing starvation-induced autophagic protein expression in renal tubular epithelial ( NRK-52E) cells. METHOD: Hank's balanced salt solution (HBSS) was used to induce NRK-52E cells to be in the state of starvation. After the intervention of HBSS for 0, 0.5,1, 2 and 6 hours, firstly, the protein expression of microtubule-associated protein 1 light chain 3(LC3 I/II), which is a key protein in autophagy, was detected. Secondly, the protein expressions of mammalian target of rapamycin (mTOR) and phosphorylated-mTOR Ser2448 (p-mTOR S2448) were examined. And then, after the co-treatment of rhein (5 mg x L(-1)) and HBSS (1 mL) without or with mTOR inhibitor, rapamycin (100 nmol x L(-1)), the protein expressions of LC3 I/II, mTOR and p-mTOR S2448 were tested, respectively. RESULT: HBSS could induce the up-regulation of LC3 II and the down-regulation of p-mTOR S2448 at protein expression level in NRK-52E cells. The co-treatment of rhein and HBSS could reversely regulate the protein expressions of LC3 II and p-mTOR S2448 in NRK-52E cells significantly. The co-treatment of rapamycin, rhein and HBSS could recover the level of LC3 II protein expression in HBSS-intervened NRK-52E cells. CONCLUSION: HBSS induces autophagy in renal tubular epithelial cells by inhibiting mTOR signaling pathway activation. Rhein reduces the autophagic protein expression in renal tubular epithelial cells through regulating mTOR signaling pathway activation, which is the possible effects and molecular mechanisms.

[Mechanisms of cordycepin on improving renal interstitial fibrosis via regulating eIF2α/TGF-ß/Smad signaling pathway].

OBJECTIVE: To investigate the effects and mechanisms of cordycepin,an effective component of cordyceps militaris, on renal interstitial fibrosis (RIF) and its related eIF2α/TGF-ß/Smad signaling pathway. METHOD: Firstly, 15 C57BL/6 mice were randomly divided into 3 groups,the control group (Group A), the model group (Group B) and the cordycepin-treated group (Group C). After renal interstitial fibrotic model was successfully established by unilateral ureteral obstruction (UUO), the mice in Group C were intraperitoneally administrated with cordycepin(5 mg x kg(-1) d(-1)) and the ones in Group A and B were administrated with physiological saline for 5 days. At the end of the study, the obstructed kidneys were collected and detected for the pathological changes of RIF, and the mRNA expressions of collagen type I (Col I) and α-smooth muscle actin (α-SMA) in the kidney by Northern blot. Secondly, after renal tubular epithelial (NRK-52E) cells cultured in vitro were exposed to transforming growth factor (TGF) -ß with or without cordycepin, the mRNA expressions of Col I and collagen type IV( Col IV) by Northern blot, and the protein expressions of eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α ( p-eIF2α), Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were tested by Western blot. RESULT: In vivo, cordycepin alleviated RIF in model mice, including improving fibrotic pathological characteristics and mRNA expressions of Col I and α-SMA. In vitro, cordycepin induced the high expression of p-elF2α, and inhibited the expressions of p-Smad2/3, Col I and Col IV induced by TGF-ß in NRK-52E cells. CONCLUSION: Cordycepin attenuates RIF in vivo and in vitro, probably by inducing the phosphorylation of eIF2α, suppressing the expression of p-Smad2/3, a key signaling molecule in TGF-ß/Smad signaling pathway, and reducing the expressions of collagens and α-SMA in the kidney.