Glucose Metabolism Indices and the Development of Chronic Kidney Disease: A Cohort Study of Middle-Aged and Elderly Chinese Persons.

Objective: Chronic kidney disease (CKD) has become a major global health issue, and abnormalities of glucose metabolism are a risk factor responsible for development of CKD. We aimed to investigate associations between glucose metabolism indices and CKD in a Chinese population and determine which index is superior for predicting incident CKD. Methods: We performed a community-based population on 5232 subjects aged ≥40 years without baseline CKD. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) ≥30 mg/g. We examined the associations of glucose metabolism indices, including fasting plasma glucose (FPG), 2-hour (2 h) oral glucose tolerance test (OGTT), hemoglobin A1c (HbA1c), fasting insulin level, homeostasis model assessment of insulin resistance (HOMA-IR), and HOMA-ß and the development of CKD. Results: With an average follow-up of 3.6 years, 6.4% of the subjects developed CKD. Pearson's correlation analysis revealed that FPG, HbA1c, fasting insulin, and HOMA-IR were all significantly correlated with UACR and eGFR. The association persisted in multivariate linear regression analysis adjusted for age and sex. Compared with other glucose indices, HOMA-IR exhibited the strongest associations with CKD in COX multivariate regression analysis (HR = 1.17, 95% CI: 1.04-1.31). Conclusion: HOMA-IR is superior to other routine indices of glucose metabolism for predicting the development of CKD in middle-aged Chinese persons. Screening with HOMA-IR may help prevent the development of CKD in the general population.

Association between uric acid lowering and renal function progression: a longitudinal study.

BACKGROUND: This study aimed to explore the association between uric acid lowering and renal function. MATERIALS AND METHODS: We conducted a population-based cohort study with 1,534 subjects for 4 years from 2012 to 2016. The population was divided into four groups according to the interquartile range of changes in serum uric acid with quartile 1 representing lower quarter. Renal function decline was defined as eGFR decreased more than 10% from baseline in 2016. Renal function improvement was defined as eGFR increased more than 10% from baseline in 2016. Cox regression analysis was used to calculate the hazard ratio (HR) and 95% confidence interval (CI). RESULTS: In the adjusted Cox regression models, compared to quartile 4, quartile 1 (HR = 0.64, 95% CI [0.49-0.85]), quartile 2 (HR = 0.65, 95% CI [0.50-0.84]) and quartile 3 (HR = 0.75, 95% CI [0.58-0.96]) have reduced risk of renal function decline. An increasing hazard ratio of renal function improvement was shown in quartile 1 (HR = 2.27, 95% CI [1.45-3.57]) and quartile 2 (HR = 1.78, 95% CI [1.17-2.69]) compared with quartile 4. CONCLUSIONS: Uric acid lowering is associated with changes in renal function. The management of serum uric acid should receive attention in clinical practice and is supposed to be part of the treatment of chronic kidney disease.

Intraoperative radiotherapy (IORT) versus whole-breast external beam radiotherapy (EBRT) in early stage breast cancer: results from SEER database.

PURPOSE: Intraoperative radiotherapy (IORT) has emerged as an alternative to whole-breast external beam radiotherapy (EBRT) for early breast cancer. This study aimed to investigate the risk factors for survival after IORT or whole-breast EBRT in breast cancer patients. MATERIALS AND METHODS: Breast cancer patients undergoing IORT or whole-breast EBRT were included from the surveillance, epidemiology, and end results database. Risk factors for overall survival (OS) and cancer-specific survival (CSS) were identified by Cox proportional hazards regression analysis. RESULTS: The IORT and EBRT groups did not differ significantly in OS and CSS. T2 stage (tumor size > 2 cm) was associated with poorer OS (aHR 3.49, 95% CI 1.05-11.62, P = 0.042), whereas ER-positive tumors were associated with better OS (aHR 0.26, 95% CI 0.09-0.76, P = 0.014). CONCLUSION: IORT was not inferior than EBRT considering the OS and CSS in the short-term follow-up of early breast cancer. It may be a reasonable alternative to EBRT for early breast cancer in select patients with favorable tumor size and receptor status, given the need for long-term monitoring of local control and radiation toxicity.

Discordant associations of lipid parameters with albuminuria and chronic kidney disease: a population-based study.

BACKGROUND: Although dyslipidemia is related to the pathogenesis of renal insufficiency, which routinely available lipid measure is more applicable in estimation of kidney function is still uncertain. Our objective was to evaluate inconsistent associations of lipid profiles with both albuminuria and chronic kidney disease (CKD). METHODS: We performed a population-based study in 9730 subjects aged 40 years or older. Definitions of abnormalities in albumin excretion were according to the latest guidelines of American Diabetes Association's Standards of Medical Care. CKD was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min per 1.73 m(2) or the presence of albuminuria. RESULTS: There were 2274 (23.4%) participants categorized as low-grade albuminuria, 639 (6.6%) participants categorized as increased urinary albumin excretion and 689 (7.1%) participants categorized as CKD. Triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), Non HDL-C to HDL-C ratio, TG to HDL-C ratio were significantly correlated with urinary albumin to creatinine ratio (ACR), serum creatinine and eGFR (all P < 0.0001). Compare with other lipid parameters, TG to HDL-C ratio have shown the strongest correlation with increased odds of both increased urinary albumin excretion and CKD. No significant associations between lipid parameters and low-grade albuminuria were observed after adjustments for potential confounding factors. CONCLUSION: Our study lends support to discordant associations of lipid parameters with albuminuria and renal function. TG to HDL-C ratio is a better marker than other routine lipid measures for identifying renal insufficiency and should be given more consideration in the clinical practice.

Association between habitual daytime napping and metabolic syndrome: a population-based study.

OBJECTIVE: Our objective was to evaluate the association between habitual daytime napping and the prevalence of metabolic syndrome. MATERIALS AND METHODS: We conducted a population-based study of 8,547 subjects aged 40 years or older. Metabolic syndrome was defined according to a harmonized definition from a joint statement and the recommended thresholds for the Chinese population. Information about sleep duration was self-reported. RESULTS: The prevalence of metabolic syndrome in the no daytime napping group, the 0 to 1 hour daytime napping group and the more than 1 hour daytime napping group were 35.0%, 36.0% and 44.5% among the females (P<0.0001). Increased daytime napping hours were positively associated with parameters of metabolic syndrome in the female subjects, including waist circumference, systolic blood pressure, triglycerides and fasting plasma glucose (P<0.05 for all). Multivariate adjusted logistic regression analysis revealed that, compared to the no habitual daytime napping females, napping for more than 1 hour was independently associated with an increased prevalence of metabolic syndrome (odds ratio 1.39, 95% confidence interval, 1.13-1.72). Compared to the female subjects in the no daytime napping group, those habitually napped for more than 1 hour exhibited 46% and 26% increases in the prevalence of central obesity and hypertriglyceridemia (all P<0.05). No statistically significant associations were detected between daytime napping hours and metabolic syndrome among the male subjects. CONCLUSION: Daytime napping is associated with an increased prevalence of metabolic syndrome in middle-aged non-obese Chinese women.

Changes in biological behaviors of rat dermal fibroblasts induced by high expression of MMP9.

BACKGROUND: The high level of matrix metalloproteinase 9 (MMP9) is thought to slow down the healing of diabetic foot ulcers. Whether it can influence the biological behaviors of skin fibroblasts and affect wound healing is still unclear. The present study aimed to observe changes in the biological behaviors of rat dermal fibroblasts induced by high expression of MMP9 and to clarify the possible mechanisms of wound healing for diabetic foot. METHODS: A cell model of skin fibroblast with high expression of MMP9 was established by co-culture of high glucose (22.0 mmol/L) and homocysteine (100 µmol/L). A control group was incubated with normal glucose (5.5 mmol/L). Realtime PCR, ELISA and gelatin zymography were used to detect the MMP9 mRNA, protein expression and activity of MMP9. Flow cytometry, CCK-8, ELISA assay, scratch test and transwell were used to detect cell proliferation, viability, collagen (hydroxyproline) secretion, horizontal migration and vertical migration of cells. The data were expressed as mean±SD. P value less than 0.05 was considered statistically significant. RESULTS: The expression of MMP9 mRNA, protein levels and the activity of MMP9 were much higher in the high MMP9 group than in the control group (7.05±1.02 vs. 1.00±0.00, 206.9±33.6 pg/mL vs. 40.4±5.9 pg/mL, and 1.47±0.13 vs. 0.57±0.12, respectively, P<0.01). The proportion of S-phase cells, proliferation index, cell viability, collagen (hydroxyproline) secretion, horizontal migration rate and the number of vertical migration cells were lower in the high MMP9 group than in the control group (P<0.01). CONCLUSION: Fibroblasts with a high expression of MMP9 decreased proliferation, activity, secretion and migration of collagens, suggesting that MMP9 may inhibit the biological behaviors of fibroblasts.

Sdc1 overexpression inhibits the p38 MAPK pathway and lessens fibrotic ventricular remodeling in MI rats.

Expression of the proteoglycan syndecan-1 (Sdc1) is increased in rats with myocardial infarction (MI). This study investigated the effects of Sdc1 overexpression on ventricular remodeling and cardiac function in MI and explored the possible mechanism through in vivo transfection of rats with recombinant adenovirus-carrying rat Sdc1 cDNA. Sprague-Dawley rats (n = 48) underwent intramyocardial injection in the marginal zone of the infarcted area immediately after ligation of the left anterior descending artery. The rats were divided into four groups according to the solution injected: MI Ad-GFP-Sdc1 transfection group, MI Ad-GFP control group, MI saline group, and sham operation group. Cardiac function and collagen expression of each group were examined, and the roles of inflammation, apoptosis, and p38 MAKP signal transduction pathway were investigated. Compared with the rats in the sham operation group, ventricular weight and collagen content increased in MI rats, and cardiac function declined. Substantial inflammatory cell infiltration was seen in the marginal zone of the infarction area, and a great number of myocardial cells were apoptotic. The p38 MAPK signaling pathway was clearly activated. Rats in the MI Ad-GFP-Sdc1 transfection group showed decreased ventricular weight, reduced collagen synthesis, and significant improvement of ventricular remodeling and cardiac function. Post-MI inflammatory cell infiltration and apoptosis was reduced, and the p38 MAPK signaling pathway was inhibited. Overexpression of Sdc1 can improve post-MI ventricular remodeling, and it is possible that the improvement is achieved through reducing apoptosis and suppressing inflammatory response and through the p38 MAPK signal transduction pathway.

The biological behaviors of rat dermal fibroblasts can be inhibited by high levels of MMP9.

AIMS: To explore the effects of the high expression of MMP9 on biological behaviors of fibroblasts. METHODS: High glucose and hyperhomocysteine were used to induce MMP9 expression in skin fibroblasts. Cell proliferation was detected by flow cytometry and cell viability by CCK-8. ELISA assay was used to detect collagen (hydroxyproline) secretion. Scratch test was employed to evaluate horizontal migration of cells and transwell method to evaluate vertical migration of cells. RESULTS: The mRNA and protein expressions of MMP9 and its protease activity were significantly higher in cells treated with high glucose and hyperhomocysteine than those in control group. At the same time, the S-phase cell ratio, proliferation index, cell viability, collagen (hydroxyproline) secretion, horizontal migration rate, and the number of vertical migration cells decreased in high-glucose and hyperhomocysteine-treated group. Tissue inhibitor of metalloproteinase 1 (TIMP1), which inhibits the activity of MMP9, recovered the above biological behaviors. CONCLUSIONS: High expression of MMP9 in skin fibroblasts could be induced by cultureing in high glucose and hyperhomocysteine medium, which inhibited cell biological behaviors. Inhibitions could be reversed by TIMP1. The findings suggested that MMP9 deters the healing of diabetic foot ulcers by inhibiting the biological behaviors of fibroblasts.

[Effects of matrix metallopeptidase 9 on the proliferation, apoptosis, type I and III procollagen synthesis of rat dermal fibroblasts].

OBJECTIVE: To explore the effects of matrix metallopeptidase 9 (MMP-9) on the proliferation, apoptosis, type I and III procollagen synthesis of rat dermal fibroblasts. METHODS: Lipopolysaccharide (LPS) at 0.1 and 1.0 µg/ml was used to stimulate fibroblasts to up-regulate the expression of MMP-9 for 18 and 48 h. And then RNA interference was employed to inhibit the high expression of MMP-9. Cell proliferation was tested by CCK-8, cell apoptosis by flow cytometry and type I and III procollagen expressions by quantitative reverse transcriptase PCR (qRT-PCR). RESULTS: The MMP-9 expression of fibroblasts increased after the stimulation of LPS. And the 1.0 µg/ml LPS stimulation of 48 hours was 14.25 times of mRNA expression and 2.31 times of protein expression versus that of the normal group (both P < 0.05). The RNA interference obviously inhibited the high expression of MMP-9. The mRNA expression was 1/8 and protein expression 1/3 (both P < 0.05) as compared with the control group. Cell proliferation decreased with the rising expression of MMP-9 to some extent [(1.08 ± 0.08) vs (1.18 ± 0.09), P < 0.05] and improved after the inhibition of high expression of MMP-9 [(1.78 ± 0.17) vs (1.53 ± 0.15), P < 0.01]. There was no change of apoptosis accompanied with high expression of MMP-9 (P > 0.05). Apoptosis decreased after the inhibition of high expression of MMP-9 for 48 hours (3.53% ± 0.22% vs 4.47% ± 0.46%, P < 0.05). The synthesis of type I procollagen was the same no matter up-regulation or down-regulation of MMP-9 expression (P > 0.05). As the expression of MMP-9 increased, the synthesis of type III procollagen decreased (P < 0.01), but not increased by 1.02 folds after the inhibited expression of MMP-9 (P > 0.05). CONCLUSION: MMP-9 can affect the biological behaviors of rat dermal fibroblasts.

[The effects of glucose fluctuation on resistin].

OBJECTIVE: To explore the effect of glucose fluctuation on resistin. METHODS: The phorbol-12-myristate-13-acetate(PMA)-activated and differentiated U937 cells were exposed to experimental condition for 3 days, three groups of cells were formed, each one receiving the following fresh medium every 6 hours, respectively: (1) continuous 11.1 mmol/L glucose concentration medium (Con group), (2) continuous 22.2 mmol/L glucose concentration medium (CHG group), (3) alternating 11.1 mmol/L glucose concentration and 22.2 mmol/L glucose concentration medium every 6 hours (IHG group). The supernatants of cell median at the last 6 hours were collected to test resistin concentration. Besides, 92 subjects were selected and classified into three groups according to the results of oral glucose tolerance test: normal glucose tolerance group (NGT group, n=30), impaired glucose tolerance patients (IGT group, n=31) and newly diagnosed type 2 diabetes patients (T2DM group, n=31). Blood glucose and serum resistin levels were measured at 0 h and 1 h during oral glucose tolerance test (OGTT) to compare the glucose fluctuation (ΔGlu1-0) and the change of serum resistin level (ΔlnRes1-0) among the three groups. RESULTS: Resistin concentration in the Con, CHG and IHG group was (73.62±5.07) ng/L, (97.78±7.00) ng/L and (212.49±28.81) ng/L respectively and in IHG group it was higher as compared with the other two groups (P<0.05). ΔGlu1-0 in NGT, IGT and T2DM group was (2.31±2.30) mmol/L, (5.70±2.08) mmol/L and (8.41±2.63) mmol/L respectively; ΔGlu1-0 increased gradually in all the three groups (P<0.05). Serum resistin level from 0 h to 1 h in the NGT group was 6.41 (1.52-15.76) µg/L to 6.96 (1.52-22.70) µg/L, in the IGT group 5.47 (1.49-24.09) µg/L to 9.12 (1.27-21.94) µg/L and in the T2DM group 5.77 (1.11-30.10) µg/L to 9.27(1.02-48.15) µg/L. In the IGT and T2DM group serum resistin level increased from 0 h to 1 h (P<0.05), but no difference was observed in the NGT group (P>0.05). ΔlnRes1-0 in these 3 groups was (0.05±0.05) µg/L, (0.25±0.04) µg/L and (0.37±0.03) µg/L respectively and the change in the T2DM group was significant as compared with that in the NGT group, ΔlnRes1-0 was positively correlated with ΔGlu1-0 (r=0.23, P=0.02). CONCLUSION: Glucose fluctuation induced monocyte/macrophage to secrete resistin, greater the glucose fluctuation, greater the change of amplitude of serum resistin.