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1.
Menopause ; 2019 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-31663988

RESUMO

OBJECTIVE: Although duration of reproductive years and time since menopause were previously implicated in the metabolic syndrome, the evidence is more limited. Few of the previous studies were able to take into account related reproductive variables simultaneously. The aim of the present study was to explore the influence of these two reproductive factors on the prevalence of metabolic syndrome in postmenopausal parous women from Southeast China. METHODS: In all, 1,536 postmenopausal parous women were recruited. Self-reported information about reproductive status, including age at menarche, age at menopause, number of children, prepregnancy body weight, and oral contraceptive use, was collected, and duration of reproductive years and time since menopause were calculated. Clinical parameters related with metabolic syndrome were also measured. RESULTS: Longer duration of reproductive years was significantly related with increased presence of the metabolic syndrome (odds ratio [OR] 1.570, 95% confidence interval [CI] 1.091, 2.259 for tertile 2 group; OR 1.850, 95% CI 1.163, 2.944 for tertile 3 group; P for trend = 0.010). Women with more than 20 years since menopause were more likely to experience metabolic syndrome (OR 2.422, 95% CI 1.109, 5.286, P = 0.026) and elevated blood pressure (OR 3.239, 95% CI 1.406, 7.458, P = 0.006) when compared with those with less than 10 years since menopause. CONCLUSIONS: Longer duration of reproductive years and time since menopause were associated with higher prevalence of metabolic syndrome in postmenopausal parous women from Southeast China.

2.
JAMA Cardiol ; 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31365039

RESUMO

Importance: Whether optimal cardiovascular health metrics may counteract the risk of cardiovascular events among patients with prediabetes or diabetes is unclear. Objective: To investigate the associations of ideal cardiovascular health metrics (ICVHMs) with subsequent development of cardiovascular disease (CVD) among participants with prediabetes or diabetes as compared with participants with normal glucose regulation. Design, Setting, and Participants: The China Cardiometabolic Disease and Cancer Cohort Study was a nationwide, population-based, prospective cohort study of 20 communities from various geographic regions in China. The study included 111 765 participants who were free from CVD or cancer at baseline. Data were analyzed between 2011 and 2016. Exposures: Prediabetes and diabetes were defined according to the American Diabetes Association 2010 criteria. Seven ICVHMs were adapted from the American Heart Association recommendations. Main Outcomes and Measures: The composite of incident fatal or nonfatal CVD, including cardiovascular death, myocardial infarction, stroke, and hospitalized or treated heart failure. Results: Of the 111 765 participants, 24 881 (22.3%) had normal glucose regulation, 61 024 (54.6%) had prediabetes, and 25 860 (23.1%) had diabetes. Mean (SD) age ranged from 52.9 (8.6) years to 59.4 (8.7) years. Compared with participants with normal glucose regulation, among participants with prediabetes, the multivariable-adjusted hazard ratio for CVD was 1.34 (95% CI, 1.16-1.55) for participants who had 1 ICVHM or less and 0.57 (95% CI, 0.43-0.75) for participants who had at least 5 ICVHMs; among participants with diabetes, the hazard ratios for CVD were 2.05 (95% CI, 1.76-2.38) and 0.80 (95% CI, 0.56-1.15) for participants who had 1 ICVHM or less and at least 5 ICVHMs, respectively. Such pattern of association between ICVHM and CVD was more prominent for participants younger than 55 years (prediabetes and at least 5 ICVHMs: hazard ratio [HR], 0.32; 95% CI, 0.16-0.63; 1 ICVHM or less: HR, 1.58, 95% CI, 1.13-2.21; diabetes and at least 5 ICVHMs: HR, 0.99; 95% CI, 0.44-2.26; 1 ICVHM or less: HR, 2.46; 95% CI, 1.71-3.54; compared with normal glucose regulation) than for participants 65 years or older (prediabetes and at least 5 ICVHMs: HR, 0.80; 95% CI, 0.50-1.26; 1 ICVHM or less: HR, 1.01; 95% CI, 0.79-1.31; diabetes and at least 5 ICVHMs: HR, 0.79; 95% CI, 0.46-1.35; 1 ICVHM or less: HR, 1.73; 95% CI, 1.36-2.22, compared with normal glucose regulation; P values for interaction ≤.02). Additionally, the hazard ratio for CVD per additional ICVHM was 0.82 (95% CI, 0.79-0.86) among participants with prediabetes and was 0.85 (95% CI, 0.80-0.89) among participants with diabetes. Conclusions and Relevance: Participants with prediabetes or diabetes who had 5 or more ICVHMs exhibited lower or no significant excess CVD risks compared with the participants with normal glucose regulation.

3.
Endocr Pract ; 25(11): 1176-1183, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31414910

RESUMO

Objective: Obesity has become a major worldwide health challenge. Macrosomic infants are more likely to experience type 2 diabetes mellitus, obesity and hypertension in adulthood. However, whether macrosomia increases the risk of maternal adiposity later in life is still unknown. Methods: One thousand nine hundred eighty-six unrelated parous women of Chinese Han ancestry aged from 40 to 76 years were enrolled. Self-reported information about reproductive status, including age at menarche, number of children, previous delivery of macrosomic infants, and body weight before and after pregnancy were obtained from personal interview by trained interviewers using a standard questionnaire. Macrosomia was defined as birth weight greater than 4,000 g. Adiposity indexes were measured or calculated. Results: Prior delivery of macrosomia was associated with an increased risk of having obesity in parous women with normal weight before pregnancy (odds ratio [OR] = 1.840; 95% confidence interval [CI] 1.028, 3.294; P = .040), as well as a higher risk of overweight/obesity in parous women with normal weight after pregnancy (OR = 1.777; 95% CI 1.131, 2.794; P = .013). In addition, previous delivery of macrosomia was related with 1.919 (95% CI 1.207, 3.050; P = .006) times higher risk of overweight/obesity in parous women with normal weight before and after pregnancy. Conclusion: The present study suggests that prior delivery of macrosomia may be an independent risk factor for adiposity later in life in parous women with normal weight before and/or after pregnancy. Abbreviations: BMI = body mass index; CI = confidence interval; OR = odds ratio; WC = waist circumference; WHR = waist-to-hip ratio; WHtR = waist-to-height ratio.


Assuntos
Diabetes Mellitus Tipo 2 , Macrossomia Fetal , Adiposidade , Adulto , Idoso , Índice de Massa Corporal , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade , Razão de Chances , Gravidez , Estudos Prospectivos , Fatores de Risco
4.
J Diabetes Res ; 2019: 9387358, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31205953

RESUMO

Aims: Fibroblast growth factor 21 (FGF21) is closely linked with metabolic disorders including diabetes. Evidences suggested that FGF21 may play a protective role against diabetic kidney disease (DKD). However, the relationship between genetic variants in the FGF21 gene region and DKD remains unknown. In our study, we aimed to investigate the association of genetic variations in this gene region with DKD and DKD-related clinical traits. Materials and Methods: We recruited 1340 Han Chinese participants with type 2 diabetes, including 596 DKD patients and 744 patients who was diagnosed with diabetes for more than 5 years but did not progress to DKD. Three single-nucleotide polymorphisms were selected (rs2071699, rs838136, and rs499765) and genotyped. The association between these SNPs and DKD as well as DKD-related quantitative traits was analyzed. Results: We did not find any significant association between these SNPs and susceptibility to DKD in the present study. However, a significant association with estimated glomerular filtration rate (eGFR) was detected: in the non-DKD group, rs838136 was significantly associated with eGFR under an additive model (ß = 0.013 ± 0.006, P = 0.0295, ß was calculated for log10eGFR) as well as a recessive model (P = 0.0385) and rs499765 was associated with eGFR under a dominant model (P = 0.0411) and in the DKD group, rs499765 showed a trend toward association with eGFR under an additive model (ß = -0.022 ± 0.012, P = 0.0820, ß was calculated for log10eGFR) and showed a significant association with eGFR under a dominant model (P = 0.0182). Conclusions: Our findings indicated that genetic variations adjacent to FGF21 were associated with eGFR in Chinese diabetic patients.

5.
Diabetes Care ; 42(8): 1539-1548, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31152120

RESUMO

OBJECTIVE: Uncertainty remains regarding the predictive value of various glycemic measures as they relate to the risk of diabetes and its complications. Using the cutoffs recommended by the American Diabetes Association's 2010 criteria, we determined the associations of fasting plasma glucose (FPG), 2-h postload glucose (2h-PG), and HbA1c with the outcomes. RESEARCH DESIGN AND METHODS: Baseline medical history, FPG, 2h-PG, and HbA1c were obtained from a population-based cohort of 193,846 adults aged ≥40 years in China during 2011-2012. A follow-up visit was conducted during 2014-2016 in order to assess incident diabetes, cardiovascular disease (CVD), cancer, and mortality. RESULTS: We documented 8,063 cases of diabetes, 3,014 CVD-related events, 1,624 cases of cancer, and 2,409 deaths during up to 5 years of follow-up. Multivariable-adjusted risk ratios (95% CIs) of diabetes associated with prediabetes based on FPG of 100-125 mg/dL, 2h-PG of 140-199 mg/dL, or HbA1c of 5.7-6.4% (39-47 mmol/mol) were 1.60 (1.43-1.79), 2.72 (2.43-3.04), and 1.49 (1.36-1.62), respectively. Restricted cubic spline analyses suggested J-shaped associations of FPG, 2h-PG, and HbA1c levels with CVD, cancer, and mortality. Multivariable-adjusted hazard ratios (95% CIs) associated with untreated diabetes based on FPG ≥126 mg/dL, 2h-PG ≥200 mg/dL, or HbA1c ≥6.5% (48 mmol/mol) were 1.18 (1.05-1.33), 1.31 (1.18-1.45), and 1.20 (1.07-1.34) for CVD; 1.10 (0.92-1.32), 1.44 (1.25-1.67), and 1.08 (0.92-1.28) for cancer; and 1.37 (1.20-1.57), 1.57 (1.41-1.76), and 1.33 (1.17-1.52) for mortality, respectively. 2h-PG remained significantly associated with outcomes in models including FPG and HbA1c as spline terms. Furthermore, 2h-PG significantly improved the ability of the C statistic to predict diabetes, CVD, and mortality. CONCLUSIONS: 2h-PG remains independently predictive of outcomes in models including FPG and HbA1c. Therefore, in addition to FPG and HbA1c, routine testing of 2h-PG should be considered in order to better assess the risks of outcomes.

6.
J Diabetes ; 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170331

RESUMO

BACKGROUND: This study investigated the association between birth weight and diabetes in a Chinese population, and the effects of body mass index (BMI) and lifestyle factors in later life on this association. METHODS: Data from 49 118 participants aged ≥40 years with recalled birth weight from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study, a nationwide population-based cohort, were used. Diabetes diagnosis was based on oral glucose tolerance tests and HbA1c measurements. Logistic regression models were used to evaluate the association of birth weight and risk of diabetes in later life. RESULTS: Increased risk of diabetes was associated with lower or higher birth weight. Compared with individuals with a birth weight of 2500 to 3499 g, the odds ratios (ORs) and 95% confidence intervals (CIs) of diabetes for individuals with a birth weight of <2500, between 3500 and 3999, and ≥4000 g were 1.28 (1.11-1.47), 1.11 (1.04-1.19), and 1.20 (1.07-1.34), respectively. Significant associations were prominent in participants with a current BMI ≥24 kg/m2 , but not detected in those with a normal BMI (OR 1.20 [95% CI 0.96-1.49], 1.11 [95% CI 0.98-1.25], and 1.10 [95% CI 0.89-1.37], respectively). Moreover, there was no increased risk of diabetes in individuals with a low birth weight but with healthy dietary habits (OR 0.94; 95% CI 0.68-1.29) or ideal physical activity (OR 1.41; 95% CI 0.97-2.04). CONCLUSIONS: A U-shaped association was observed between birth weight and the risk of diabetes. Healthy lifestyles (healthy dietary habits or ideal physical activity) may eliminate the negative effects of low birth weight in the development of diabetes, but not the effect of high birth weight.

7.
Int J Mol Med ; 43(5): 2187-2198, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30896786

RESUMO

Metformin serves an important role in improving the functions of endothelial progenitor cells (EPCs). MicroRNAs (miRNAs), small non­coding RNAs, have been investigated as significant regulators of EPC vascular functions. The present study investigated the molecular crosstalk between metformin and miRNA­130a (miR­130a) in the functions of EPCs exposed to palmitic acid (PA). Isolated EPCs were treated with metformin, PA, and metformin + PA, respectively. Cell Counting Kit­8, Transwell and Matrigel assays were performed to detect the proliferation, migration and tube formation ability of EPCs following different treatments. The expression of miR­130a, phosphatase and tensin homolog (PTEN) and phosphorylated­AKT was analyzed by reverse transcription­quantitative polymerase chain reaction and western blotting. The specific mechanism underlying the function of metformin in EPCs was further elucidated by transfecting miR­130a mimics and inhibitor to overexpress and inhibit the expression of miR­130a in EPCs, respectively. EPCs exhibited impaired functions of proliferation (P<0.01 compared with the control), migration (P<0.01 compared with the control) and tube formation (P<0.01 compared with the control) following treatment with PA, and the expression levels of miR­130a and PTEN were decreased and increased, respectively. However, the presence of metformin, or the overexpression of miR­130a using miR­130a mimic alleviated the impairment of angiogenesis and proliferation, decreased the expression of PTEN and activated the phosphoinositide­3 kinase/AKT pathway in EPCs exposed to PA. By contrast, downregulating the expression of miR­130a with a miR­130a inhibitor reversed the metformin­mediated protection. These results demonstrate the beneficial effect of miR­130a/PTEN on EPC functions, which can be regulated by metformin. The effects of metformin on improving PA­induced EPC dysfunction are mediated by miR­130a and PTEN, which may assist in the prevention and/or treatment of diabetic vascular disease.


Assuntos
Células Progenitoras Endoteliais/patologia , Metformina/farmacologia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Ácido Palmítico/toxicidade , Animais , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Citoproteção/efeitos dos fármacos , Regulação para Baixo/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , Células Progenitoras Endoteliais/metabolismo , Masculino , MicroRNAs/genética , Neovascularização Fisiológica/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Substâncias Protetoras/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley
8.
J Trace Elem Med Biol ; 52: 209-215, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30732884

RESUMO

Trace elements, such as copper, zinc and selenium, have been linked to the development of metabolic syndrome. However, previous studies concerning these trace elements in association with metabolic syndrome have presented conflicting results in different countries. The aim of this study was to analyse the association between serum copper, zinc and selenium concentrations and the risk of metabolic syndrome among middle-aged and older Chinese adults. We performed a nested case-control study that included 349 individuals who developed metabolic syndrome (125 males and 224 females) during a 3-year follow-up and 349 controls matched by baseline age (±1 years), sex and area. Serum trace element concentrations were measured using atomic absorption spectrometry. The median serum selenium levels in males and females in the metabolic syndrome group were 82.2 (13.4) µg/L and 82.6 (11.1) µg/L, respectively, which were significantly higher than the serum selenium levels in the control group (p = 0.001 and p < 0.001). After adjusting for potential confounders, the odds ratios of risk for metabolic syndrome in the highest tertile of serum selenium levels were 2.72 [95% confidence interval (CI) 1.43-5.20; p for trend 0.002] for males and 5.30 (95% CI 3.31-8.74; p for trend <0.001) for females, respectively, compared with the lowest tertile. In addition, serum selenium levels were positively correlated with postprandial plasma glucose in both genders (for males: odds ratio 2.42; 95% CI 1.27-4.61; for females: odds ratio 2.11; 95% CI 1.32-3.37) and negatively associated with high-density lipoprotein in only females (odds ratio 3.21; 95% CI 1.75-5.91). These results suggest that higher levels of serum selenium might be an independent risk factor for metabolic syndrome, especially in relation to elevated postprandial plasma glucose and reduced high-density lipoprotein levels. However, we failed to demonstrate an association between copper or zinc status and metabolic syndrome or its components.


Assuntos
Cobre/sangue , Síndrome Metabólica/sangue , Selênio/sangue , Zinco/sangue , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
9.
Mol Med Rep ; 19(2): 1365-1371, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30569165

RESUMO

Type 2 diabetes mellitus (T2DM) is characterized by the dysfunction and loss of pancreatic islet ß­cells, in part due to islet amyloid deposits derived from islet amyloid polypeptide (IAPP). The glucagon­like peptide­1 (GLP­1) receptor agonist exendin­4 enhances the insulin secretory response by increasing ß­cell mass in T2DM. However, it is unknown whether exendin­4 protects ß­cells from IAPP­mediated autophagy and apoptosis. In the present study, reverse transcription­quantitative polymerase chain reaction, ELISA and western blotting were used to detected the mRNA and protein expression of insulin/hIAPP and other signaling molecules, while the mechanisms underlying these effects were also determined. Exendin­4 increased the level of insulin secretion, which was greater than that of IAPP, leading to a beneficial IAPP/insulin secretion pattern. In MIN6 cells incubated with 25 mM glucose, exendin­4 decreased the ratio of light chain 3 (LC3)­II/I, which was accompanied by an increase in p62 protein. In a hIAPP­overexpressing MIN6 cell model, exendin­4 prevented the hIAPP­induced increase in the LC3II/I ratio and decrease in p62 expression. In addition, exendin­4 pretreatment reduced hIAPP­induced activation of cleaved caspase­3, suggesting that exendin­4 may protect MIN6 cells against apoptosis. Taken together, the results highlight hIAPP as a critical mediator of ß­cell loss and suggest that the GLP­1 receptor agonist exendin­4 may be a potential therapeutic agent for hIAPP­induced ß­cell damage.


Assuntos
Autofagia/efeitos dos fármacos , Exenatida/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/efeitos dos fármacos , Animais , Apoptose/efeitos dos fármacos , Linhagem Celular , Diabetes Mellitus Tipo 2 , Glucose/metabolismo , Humanos , Insulina/metabolismo , Ilhotas Pancreáticas/metabolismo , Camundongos
10.
Mol Cells ; 41(9): 853-867, 2018 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-30165731

RESUMO

As the most common type of endocrine malignancy, papillary thyroid cancer (PTC) accounts for 85-90% of all thyroid cancers. In this study, we presented the hypothesis that SDC4 gene silencing could effectively attenuate epithelial mesenchymal transition (EMT), and promote cell apoptosis via the Wnt/ß-catenin signaling pathway in human PTC cells. Bioinformatics methods were employed to screen the determined differential expression levels of SDC4 in PTC and adjacent normal samples. PTC tissues and adjacent normal tissues were prepared and their respective levels of SDC4 protein positive expression, in addition to the mRNA and protein levels of SDC4, Wnt/ß-catenin signaling pathway, EMT and apoptosis related genes were all detected accordingly. Flow cytometry was applied in order to detect cell cycle entry and apoptosis. Finally, analyses of PTC migration and invasion abilities were assessed by using a Transwell assay and scratch test. In PTC tissues, activated Wnt/ß-catenin signaling pathway, increased EMT and repressed cell apoptosis were determined. Moreover, the PTC K1 and TPC-1 cell lines exhibiting the highest SDC4 expression were selected for further experiments. In vitro experiments revealed that SDC4 gene silencing could suppress cell migration, invasion and EMT, while acting to promote the apoptosis of PTC cells by inhibiting the activation of the Wnt/ß-catenin signaling pathway. Besides, si-ß-catenin was observed to inhibit the promotion of PTC cell migration and invasion caused by SDC4 overexpression. Our study revealed that SDC4 gene silencing represses EMT, and enhances cell apoptosis by suppressing the activation of the Wnt/ß-catenin signaling pathway in human PTC.

11.
Diabetes ; 67(7): 1441-1453, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29735607

RESUMO

Mitochondrial DNA (mtDNA) haplogroups have been associated with the incidence of type 2 diabetes (T2D); however, their underlying role in T2D remains poorly elucidated. Here, we report that mtDNA haplogroup N9a was associated with an increased risk of T2D occurrence in Southern China (odds ratio 1.999 [95% CI 1.229-3.251], P = 0.005). By using transmitochondrial technology, we demonstrated that the activity of respiratory chain complexes was lower in the case of mtDNA haplogroup N9a (N9a1 and N9a10a) than in three non-N9a haplogroups (D4j, G3a2, and Y1) and that this could lead to alterations in mitochondrial function and mitochondrial redox status. Transcriptome analysis revealed that OXPHOS function and metabolic regulation differed markedly between N9a and non-N9a cybrids. Furthermore, in N9a cybrids, insulin-stimulated glucose uptake might be inhibited at least partially through enhanced stimulation of ERK1/2 phosphorylation and subsequent TLR4 activation, which was found to be mediated by the elevated redox status in N9a cybrids. Although it remains unclear whether other signaling pathways (e.g., Wnt pathway) contribute to the T2D susceptibility of haplogroup N9a, our data indicate that in the case of mtDNA haplogroup N9a, T2D is affected, at least partially through ERK1/2 overstimulation and subsequent TLR4 activation.


Assuntos
DNA Mitocondrial/genética , Diabetes Mellitus Tipo 2/genética , Mitocôndrias/genética , Mitocôndrias/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/metabolismo , Feminino , Predisposição Genética para Doença , Haplótipos , Humanos , Espaço Intracelular , Masculino , Pessoa de Meia-Idade , Mitocôndrias/fisiologia , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Adulto Jovem
12.
BMC Cardiovasc Disord ; 18(1): 89, 2018 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-29739314

RESUMO

BACKGROUND: The skeletal muscle mass-to-visceral fat area ratio (SVR) has been linked to arterial stiffness in non-diabetic adults. We examined the association between the SVR and arterial stiffness in patients with type 2 diabetes mellitus (T2DM). METHODS: Patients with type 2 diabetes mellitus (252 men and 171 women) aged 40-75 years were enrolled and divided into three groups according to SVR tertiles. Arterial stiffness was measured as brachial-ankle pulse wave velocity (baPWV), with baPWV> 1800 mm/s defined as high. Spearman's partial correlation was used to adjust confounding factors. The odds ratio for high baPWV was determined by multiple logistic regression analyses, and receiver-operating characteristic analysis was conducted. RESULTS: SVR was associated with baPWV in Chinese patients with T2DM (Spearman's partial correlation = - 0.129, P < 0.01). SVR was found to be significantly associated with baPWV on multiple logistic regression analysis. Patients in the lower SVR tertiles had a higher OR than did those in the higher SVR tertiles, after adjusting for multiple covariates (Q1: OR = 4.33 in men and 4.66 in women; Q3: OR = 1). The area under the curve for SVR was significantly greater than that for appendicular skeletal muscle (ASM), ASM/height2, and visceral fat area (VAF) for identifying high baPWV (0.747 in men and 0.710 in women). The optimal cutoffs values of SVR for detecting high baPWV were 191.7 g/cm2 for men and 157.3 g/cm2 for women. CONCLUSIONS: SVR has an independent, negative association with arterial stiffness, and is a better risk-assessment tool than ASM, ASM/height2, and VFA in clinical practice to identify patients with type 2 diabetes at high cardiovascular risk.

13.
J Diabetes ; 10(5): 408-418, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29144059

RESUMO

BACKGROUND: A number of primary studies suggested that active smoking could be independently associated with incident diabetes. However less is known about the effect of active smoking and smoking cessation on glycemic control in patients with diabetes. The aim of this study was to evaluate the associations of active smoking and smoking cessation with glycemic control in diabetic patients. METHODS: The present was a cross-sectional study of 10 551 men and 15 297 women with diabetes from the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Risk factors for glycemic control and the association of active smoking with glycemic control were evaluated using logistic regression models. Poor glycemic control was defined as HbA1c ≥7.0%. RESULTS: Current smokers have an increased risk of poor glycemic control, and the multivariable-adjusted odds ratio (OR) and 95% confidence intervals (CI) of HbA1c ≥7.0% with current smoking were 1.49 (1.35-1.66) in men and 1.56 (1.13-2.15) in women. Further analysis demonstrated a dose-dependent relationship between active smoking and the risk of poor glycemic control in men. Former smokers who quit smoking for <10 years remained at increased risk of poor glycemic control, with the risk leveling off after 10 years of smoking cessation compared with non-smokers, but risk in former smokers was significantly lower than that in current smokers. CONCLUSIONS: Active smoking is a modifiable risk factor for poor glycemic control in Chinese diabetic patients.


Assuntos
Glicemia/efeitos dos fármacos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Abandono do Hábito de Fumar , Fumar/efeitos adversos , Adulto , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Distribuição de Qui-Quadrado , China/epidemiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Incidência , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Razão de Chances , Prevalência , Fatores de Risco , Fumar/sangue , Fumar/epidemiologia , Fatores de Tempo
14.
J Diabetes Complications ; 32(2): 150-156, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29191431

RESUMO

AIMS: To determine the epidemiological characteristics of lower extremity arterial disease (LEAD) in high-risk patients and identify practical gaps in LEAD management. METHODS: This cross-sectional study consecutively enrolled 10681 patients with type 2 diabetes from 30 hospitals across China from June 2016 to January 2017. All patients were assessed for LEAD by the Ankle-Brachial Index in conjunction with lower limb ultrasonography according to local guidelines. RESULTS: The mean age of patients was 64.2 years, and the median duration of diabetes was 9.0 years. The overall prevalence of LEAD was 21.2%, with 10.6% of patients diagnosed with LEAD before enrollment and 11.8% newly diagnosed at the present visit. Patients with older age, hypertension and dyslipidemia as well as those who smoked were at higher risk of developing LEAD. Only 55.0%, 28.2%, and 42.5% of participating patients reached the guideline-recommended goals for glycemic, blood pressure, and lipid control, respectively. Anti-hypertensive agents, lipid lowering therapies, anti-platelet agents, and vasodilators were underused, especially in newly diagnosed LEAD patients (44.1%, 46.2%, 35.3%, and 31.7%, respectively). CONCLUSIONS: Despite the high prevalence of LEAD, it was still found to be underdiagnosed and undertreated in Chinese diabetes patients. More efforts should be directed at encouraging awareness of early LEAD and achieving guideline-recommended goals in type 2 diabetes patients.

15.
J Cell Mol Med ; 22(1): 89-100, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28799229

RESUMO

Recently, the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin, a major anti-hyperglycaemic agent, has received substantial attention as a therapeutic target for cardiovascular diseases via enhancing the number of circulating endothelial progenitor cells (EPCs). However, the direct effects of sitagliptin on EPC function remain elusive. In this study, we evaluated the proangiogenic effects of sitagliptin on a diabetic hind limb ischaemia (HLI) model in vivo and on EPC culture in vitro. Treatment of db/db mice with sitagliptin (Januvia) after HLI surgery efficiently enhanced ischaemic angiogenesis and blood perfusion, which was accompanied by significant increases in circulating EPC numbers. EPCs derived from the bone marrow of normal mice were treated with high glucose to mimic diabetic hyperglycaemia. We found that high glucose treatment induced EPC apoptosis and tube formation impairment, which were significantly prevented by sitagliptin pretreatment. A mechanistic study found that high glucose treatment of EPCs induced dramatic increases in oxidative stress and apoptosis; pretreatment of EPCs with sitagliptin significantly attenuated high glucose-induced apoptosis, tube formation impairment and oxidative stress. Furthermore, we found that sitagliptin restored the basal autophagy of EPCs that was impaired by high glucose via activating the AMP-activated protein kinase/unc-51-like autophagy activating kinase 1 signalling pathway, although an autophagy inhibitor abolished the protective effects of sitagliptin on EPCs. Altogether, the results indicate that sitagliptin-induced preservation of EPC angiogenic function results in an improvement of diabetic ischaemia angiogenesis and blood perfusion, which are most likely mediated by sitagliptin-induced prevention of EPC apoptosis via augmenting autophagy.

16.
Biochem Biophys Res Commun ; 496(2): 245-252, 2018 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-29180018

RESUMO

Sepsis, one of the most fatal diseases worldwide, often leads to multiple organ failure, mainly due to uncontrolled inflammatory responses. Despite accumulating knowledge obtained in recent years, effective drugs to treat sepsis in the clinic are still urgently needed. Isoliquiritigenin (ISL), a chalcone compound, has been reported to exert anti-inflammatory properties. However, little is known about the effects of ISL on sepsis and its related complications. In this study, we investigated the potential protective effects of ISL on lipopolysaccharide (LPS)-induced injuries and identified the mechanisms underlying these effects. ISL inhibited inflammatory cytokine expression in mouse primary peritoneal macrophages (MPMs) exposed to LPS. In an acute lung injury (ALI) mouse model, ISL prevented LPS-induced structural damage and inflammatory cell infiltration. Additionally, pretreatment with ISL attenuated sepsis-induced lung and liver injury, accompanied by a reduction in inflammatory responses. Moreover, these protective effects were mediated by the nuclear factor kappa B (NF-κB) pathway-mediated inhibition of inflammatory responses in vitro and in vivo. Our study suggests that ISL may be a potential therapeutic agent for sepsis-induced injuries.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Chalconas/farmacologia , Pulmão/efeitos dos fármacos , Sepse/tratamento farmacológico , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/imunologia , Lesão Pulmonar Aguda/patologia , Animais , Citocinas/genética , Citocinas/imunologia , Modelos Animais de Doenças , Regulação da Expressão Gênica , Células Hep G2 , Humanos , Lipopolissacarídeos , Fígado/efeitos dos fármacos , Fígado/imunologia , Fígado/patologia , Pulmão/imunologia , Pulmão/patologia , Macrófagos Peritoneais/efeitos dos fármacos , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/genética , NF-kappa B/imunologia , Cultura Primária de Células , Sepse/induzido quimicamente , Sepse/imunologia , Sepse/patologia
17.
Med Sci Monit ; 23: 4304-4311, 2017 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-28877159

RESUMO

BACKGROUND Epicardial adipose tissue (EAT) is recognized as a useful indicator for type 2 diabetes mellitus (T2DM) and obesity. However, studies on the association between vitamin D status and EAT thickness in type 2 diabetes (T2D) are limited. In this study, we aimed to evaluate the association of vitamin D (Calcifediol) status and EAT thickness (EATT) in Chinese non-obese patients with T2D. MATERIAL AND METHODS A cross-sectional study was performed among 167 non-obese T2D Chinese patients and 82 non-diabetic patients, who are age- and gender-matched during the winter months. EATT was evaluated by two-dimensional transthoracic echocardiography. Serum 25-hydroxyvitamin D [25(OH)D, Calcifediol] was examined in the diabetic patients and in the control group. RESULTS The concentration of 25(OH)D was 32.00 nmol/l (19.30-53.70 nmol/l) among diabetic patients. Most (93.4%) of the diabetic patients had hypovitaminosis D. We confirmed a clear negative association between 25(OH)D level and EATT in non-obese T2D patients (p=0.01). EATT was significantly correlated with 25(OH)D level (p=0.001) and HOMA-IR (p=0.001). Results of multivariate logistic regression analysis demonstrated increased EATT, which was remarkably associated with 25(OH)D levels (p=0.039), systolic blood pressure (SBP) (p=0.013), HOMA-IR (p=0.030), and waist circumference (p<0.001) in T2D patients after adjusting for the confounding factors. CONCLUSIONS Increased EATT was found in Chinese T2D patients with normal BMI. 25(OH)D and HOMA-IR were independently associated with increased EATT after adjusting for multiple confounders.


Assuntos
Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Pericárdio/metabolismo , Vitamina D/análogos & derivados , Tecido Adiposo/patologia , Adulto , Glicemia/metabolismo , Índice de Massa Corporal , Calcifediol/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/diagnóstico por imagem , Diabetes Mellitus Tipo 2/patologia , Ecocardiografia/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Pericárdio/patologia , Vitamina D/metabolismo , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/metabolismo , Circunferência da Cintura
19.
J Diabetes ; 9(9): 837-845, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27734593

RESUMO

BACKGROUND: Diagnosed diabetes has been associated with chronic kidney disease (CKD). However, the association between non-diabetic hyperglycemia and CKD remained uncertain. The aim of the present study was to investigate the association between different glycemic status and CKD in Chinese adults and to assess the prevalence and control of diabetes among individuals with CKD. METHODS: In all, 250 752 adults aged ≥40 years were selected from the baseline cohort of the Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Plasma glucose concentrations and biochemical and other clinical data were collected; CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min per 1.73 m2 . RESULTS: The prevalence of CKD increased gradually with deterioration of glucose metabolic status in both men and women ( P trend < 0.001 for both). Compared with individuals with normal glucose regulation, men with prediabetes and diabetes had higher risks of prevalent CKD (prediabetes odds ratio [OR] 1.15, 95% confidence interval [CI] 1.02-1.32; newly diagnosed diabetes OR 1.27, 95% CI 1.08-1.49; previously diagnosed diabetes OR 2.05, 95% CI 1.78-2.35). Similar results were observed in women, but not among those with prediabetes. In male CKD patients with diabetes, 52.1% received antidiabetic treatment and 41.8% of those treated had effective glycemic control, higher than values for females. CONCLUSIONS: Prediabetes and diabetes were associated with an increased risk of CKD in Chinese men. Control of diabetes among Chinese CKD patients is far from optimal.


Assuntos
Glicemia/metabolismo , Hiperglicemia/epidemiologia , Falência Renal Crônica/epidemiologia , Estado Pré-Diabético/epidemiologia , Idoso , China/epidemiologia , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Inquéritos e Questionários
20.
Tissue Eng Part C Methods ; 23(2): 61-71, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-27981878

RESUMO

Women younger than 40 years may face early menopause because of premature ovarian failure (POF). The cause of POF can be idiopathic or iatrogenic, especially the cancer-induced oophorectomy and chemo- or radiation therapy. The current treatments, including hormone replacement therapy (HRT) and cryopreservation techniques, have increased risk of ovarian cancer and may reintroduce malignant cells after autografting. Decellularization technique has been regarded as a novel regenerative medicine strategy for organ replacement, wherein the living cells of an organ are removed, leaving the extracellular matrix (ECM) for cellular seeding. This study aimed to produce a xenogeneic decellularized ovary (D-ovary) scaffold as a platform for ovary regeneration and transplantation. We have developed a novel decellularization protocol for porcine ovary by treatment with physical, chemical, and enzymatic methods. Using hematoxylin and eosin (H&E) staining, DAPI staining, scanning electron microscopy (SEM), and quantitative analysis, this approach proved effective in removing cellular components and preserving ECM. Furthermore, the results of biological safety evaluation demonstrated that the D-ovary tissues were noncytotoxic for rat ovarian cells in vitro and caused only a minimal immunogenic response in vivo. In addition, the D-ovary tissues successfully supported rat granulosa cell penetration ex vivo and showed an improvement in estradiol (E2) hormone secretion.


Assuntos
Matriz Extracelular/metabolismo , Ovário/citologia , Regeneração/fisiologia , Engenharia Tecidual/métodos , Tecidos Suporte , Animais , Sobrevivência Celular , Células Cultivadas , Estradiol/metabolismo , Feminino , Ratos , Medicina Regenerativa , Suínos
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