Diaozhu Lin

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.

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.

Cationic star-shaped polymer as an siRNA carrier for reducing MMP-9 expression in skin fibroblast cells and promoting wound healing in diabetic rats.

Background Excessive expression of matrix metalloproteinase-9 (MMP-9) is deleterious to the cutaneous wound-healing process in the context of diabetes. The aim of the present study was to explore whether a cationic star-shaped polymer consisting of β-cyclodextrin (β-CD) core and poly(amidoamine) dendron arms (β-CD-[D3]7) could be used as the gene carrier of small interfering RNA (siRNA) to reduce MMP-9 expression for enhanced diabetic wound healing. Methods The cytotoxicity of β-CD-(D3)7 was investigated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MMT) method in the rat CRL1213 skin fibroblast cell line. The transfection efficiency of β-CD-(D3)7/MMP-9-small interfering RNA (siRNA) complexes was determined by confocal microscopy and flow cytometry. Quantitative real time (RT) polymerase chain reaction was performed to measure the gene expression of MMP-9 after the transfection by β-CD-(D3)7/MMP-9-siRNA complexes. The β-CD-(D3)7/MMP-9-siRNA complexes were injected on the wounds of streptozocin-induced diabetic rats. Wound closure was measured on days 4 and 7 post-wounding. Results β-CD-(D3)7 exhibited low cytotoxicity in fibroblast cells, and easily formed the complexes with MMP-9-siRNA. The β-CD-(D3)7/MMP-9-siRNA complexes were readily taken up by fibroblast cells, resulting in the downregulation of MMP-9 gene expression (P<0.01). Animal experiments revealed that the treatment by β-CD-(D3)7/MMP-9-siRNA complexes enhanced wound closure in diabetic rats on day 7 post-wounding (P<0.05). Conclusion β-CD-(D3)7 may be used as an efficient carrier for the delivery of MMP-9-siRNA to reduce MMP-9 expression in skin fibroblast cells and promote wound healing in diabetic rats.

Angiotensin II regulates collagen metabolism through modulating tissue inhibitor of metalloproteinase-1 in diabetic skin tissues

We investigated the effect of angiotensin II (Ang II) on matrix metalloproteinase-1 (MMP-1)/tissue inhibitor of metalloproteinase-1 (TIMP-1) balance in regulating collagen metabolism of diabetic skin. Skin tissues from diabetic model were collected, and the primary cultured fibroblasts were treated with Ang II receptor inhibitors before Ang II treatment. The collagen type I (Coll I) and collagen type III (Coll III) were measured by histochemistry. The expressions of transforming growth factor-β (TGF-β), MMP-1, TIMP-1 and propeptides of types I and III procollagens in skin tissues and fibroblasts were quantified using polymerase chain reaction (PCR), Western blot or enzyme-linked immunosorbent assay (ELISA). Collagen dysfunction was documented by changed collagen I/III ratio in streptozotocin (STZ)-injected mice compared with controls. This was accompanied by increased expression of TGF-β, TIMP-1 and propeptides of types I and III procollagens in diabetic skin tissues. In primary cultured fibroblasts, Ang II prompted collagen synthesis accompanied by increases in the expressions of TGF-β, TIMP-1 and types I and III procollagens, and these increases were inhibited by losartan, an Ang II type 1 (AT1) receptor blocker, but not affected by PD123319, an Ang II type 2 (AT2) receptor antagonist. These findings present evidence that Ang-II-mediated changes in the productions of MMP-1 and TIMP-1 occur via AT1 receptors and a TGF-β-dependent mechanism.

Serum Gamma - Glutamyltransferase Is Associated with Albuminuria: A Population-Based Study

Background Serum γ - glutamyltransferase (GGT) is implicated in the pathogenesis of endothelial dysfunction and atherosclerosis. Albuminuria is a marker of endothelial damage and correlated with structural and functional integrity of the vasculature. Our objective was to evaluate the association between serum GGT level and prevalence of albuminuria in a Chinese population. Materials and Methods We conducted a population-based cross-sectional study in 9,702 subjects aged 40 years or older. Increased urinary albumin excretion was defined according to the urinary albumin-to-creatinine ratio (ACR) ranges greater or equal than 30 mg/g. Low-grade albuminuria was defined according to the highest quartile of ACR in participants without increased urinary albumin excretion. Results The prevalence of low-grade albuminuria and increased urinary albumin excretion were respectively 23.4% and 6.6% in this population and gradually increased across the sex-specific serum GGT quartiles (all P for trend <0.05). In logistic regression analysis, compared with subjects in the lowest quartile of serum GGT level, the adjusted odds ratios (ORs) in the highest quartile was 1.22 [95% confidence interval (CI), 1.04–1.43] for low-grade albuminuria and 1.55 (95% CI, 1.18–2.04) for increased urinary albumin excretion. In subgroup analysis, significant relationship of serum GGT level with both low-grade albuminuria and increased urinary albumin excretion were detected in women, younger subjects, overweight subjects and in those with hypertension or glomerular filtration rate greater than 90 (all P <0.05). Conclusion Serum GGT level is associated with urinary albumin excretion in middle-aged and elderly Chinese.

Role of the mevalonate pathway in specific CpG site demethylation on AGEs-induced MMP9 expression and activation in keratinocytes.

BACKGROUND Advanced glycation end products (AGEs) played an important role for the development of diabetic foot. In the present study we tried to show the mevalonate pathway and the key demethylation site(s) in the MMP-9 cis-promoter to the component of MMP-9 by AGEs in keratinocyte. METHOD Human keratinocyte cell line (HaCaT) cells were exposed to AGE-BSA. The plasmid construction and site-directed mutagenesis, dual-luciferase reporter assays, immunoblot, zymography, pull down, bisulfite sequencing PCR analysis and Western blotting were applied. RESULTS The AGE-BSA could increase and more activate the MMP9 in keratinocyte. The RhoA and ROCK1 also could be activated. These affects were blocked by the simvastatin. Meanwhile, the CpG site at -562 site was largely demethylated with AGE-BSA treatment. The cis-promoter sequences with -562 bp site methylated had a lower activity change, which had a highest expression activity and was decreased by simvastatin. Moreover, site-directed mutagenesis of CpG site (-562 bp) in the recombinant plasmid pCpGL-571 brought more reduction in activity, and the activity of methylated mutation pCpGL-571 remains decreased. CONCLUSION The cis-promoter regions of MMP9 would be methylated by AGE-BSA in keratinocyte through the mevalonate pathway, especially the -562 bp site.

Longtime napping is associated with cardiovascular risk estimation according to Framingham risk score in postmenopausal women.

Objective:Menopause can affect the physiological timing system, which could result in circadian rhythm changes and development of napping habits. Whether longtime napping in postmenopausal women is associated with cardiovascular disease is, however, still debated. The present study aims to investigate this association. Methods:We conducted a population-based study in 4,616 postmenopausal Chinese women. Information on sleep duration was self-reported. The Framingham General Cardiovascular Risk Score was calculated and used to identify participants at high risk of coronary heart disease (CHD). Results:Increased daytime napping hours were positively associated with cardiovascular disease risk factors in postmenopausal women, such as age, waist circumference, systolic blood pressure, triglycerides, fasting glucose, postload glucose, and hemoglobin A1C (all P for trend <0.05). The prevalence of high risk of CHD increased with daytime napping hours, and was 3.7%, 4.3%, and 6.9% in the no daytime napping group, the 0.1 to 1 hour group, and the more than 1 hour group, respectively (P for trend = 0.005). Compared with the no daytime napping group, postmenopausal women with daytime napping more than 1 hour had higher risk of CHD in both univariate (odds ratio 1.94, 95% CI, 1.29-2.95) and multivariate (odds ratio 1.61, 95% CI, 1.03-2.52) logistic regression analyses. No statistically significant association was detected between night sleeping hours and high risk of CHD in postmenopausal participants. Conclusions:Daytime napping is positively associated with estimated 10-year CHD risk in postmenopausal Chinese women.

Glycemic load is associated with diabetes and prediabetes among middle-aged and elderly adults in Guangzhou, china

BACKGROUND AND OBJECTIVES Previous studies have obtained conflicting findings regarding the possible associations between glycemic load (GL) indices and diabetes. In the present study, we examined cross-sectional associations between several GL indices, including the total dietary GL, the energy-adjusted GL, and the prevalence of abnormal glucose metabolism, including prediabetes and diabetes. METHODS AND STUDY DESIGN This study was conducted in Guangzhou, China from July 2011 to December 2011. It included 2,022 participants (602 men and 1,420 women), between 45 and 75 years of age. The prevalence of abnormal glucose metabolism was compared across the quartiles of GL indices to discover any potential linear correlations. Stratified analysis was conducted according to the body mass index (BMI) and waist circumference (WC) measurements. RESULTS Energy-adjusted GL was positively associated with the prevalence of diabetes and the multivariable-adjusted estimate of the OR comparing the highest versus the lowest quartile was 2.50 (95% CI, 1.49-4.19). For the stratified analysis by sex, BMI or WC, similar associations were observed. For the overweight and obese (BMI ≥24.0 kg/m2) or centrally obese (WC ≥85 cm for men or ≥80 cm for women) participants, compared to participants in the lowest quartile of energy-adjusted GL, those in the highest quartile showed an increased risk of abnormal glucose metabolism. The OR estimates were 2.25 (95% CI: 1.45-3.52) and 1.54 (95% CI: 1.06-2.25), respectively. CONCLUSIONS High dietary energy-adjusted GL is associated with the prevalence of diabetes as well as abnormal glucose metabolism among middle-aged and elderly adults.

A greater glycemic load reduction was associated with a lower diabetes risk in pre-diabetic patients who consume a high glycemic load diet

Few prospective studies evaluating the association between dietary glycemic load (GL) and diabetes have accounted for changes in GL. However, the diet of patients could be modified in response to an awareness of pre-diabetes. The aim of this study was to examine the longitudinal associations between changes in GL and the incidence of diabetes among pre-diabetic patients. We hypothesized that subjects with low and high baseline GL would show different correlations with diabetes. A total of 493 pre-diabetic patients (142 men and 351 women) between 40 and 79 years of age were included in this study. Dietary records and oral glucose tolerance tests were conducted every year. The participants were divided into low- and high-GL groups based on baseline GL. During a median 4 years of follow-up, 108 incident cases of diabetes were identified. Among participants with a high baseline GL, the incidence of diabetes increased with decreasing GL reduction, and the multivariate-adjusted HR (95% CI) was 2.34 (1.27-4.29) when comparing the lowest to the highest tertiles; however, among those with a low baseline GL, no significant association was observed. Regardless of baseline GL status, the incidence of diabetes was higher in individuals with a high follow-up GL than in those with a low follow-up GL, and the multivariate-adjusted HR (95% CI) was 1.64 (1.09-2.45). In conclusion, a greater GL reduction was associated with a lower diabetes risk in pre-diabetic patients with a high dietary GL. In patients with pre-diabetes and a low dietary GL, further reductions in GL did not show any additional effects.

Fatty liver index, albuminuria and the association with chronic kidney disease: a population-based study in China

Objectives The effects of lipid metabolism disorder on renal damage have drawn much attention. Using the fatty liver index (FLI) as a validated indicator of hepatic steatosis, this study aims to provide insight about the possible links between fatty liver and the development of chronic kidney disease (CKD). Setting Hospital. Participants We performed a population-based study on 9436 subjects aged 40 years or older. Primary and secondary outcome measures FLI is calculated using an algorithm based on body mass index, waist circumference, triglycerides and γ-glutamyltransferase. Increased urinary albumin excretion was defined according to the urinary albumin to creatinine ratio ranges ≥30 mg/g. CKD was defined as estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m² or presence of albuminuria. Results There were 620 (6.6%) subjects categorised to have increased urinary albumin excretion and 753 (8.0%) subjects categorised to have CKD. Participants with higher FLI had increased age, blood pressure, low-density lipoprotein cholesterol, fasting plasma glucose, fasting insulin and decreased eGFR level. Prevalence of increased urinary albumin excretion and CKD tended to increase with the elevated FLI quartiles. In logistic regression analysis, compared with subjects in the lowest quartile of FLI, the adjusted ORs in the highest quartile were 2.30 (95% CI 1.36 to 3.90) for increased urinary albumin excretion and 1.93 (95% CI 1.18 to 3.15) for CKD. Conclusion Hepatic steatosis evaluated by FLI is independently associated with increased urinary albumin excretion and prevalence of CKD in middle-aged and elderly Chinese.