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1.
Metabolism ; 120: 154779, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-33895182

RESUMO

BACKGROUND: Metabolic dysfunction-associated fatty liver disease (MAFLD) has been proposed and diagnosed based on modified criteria. However, evidence for the risks of developing subclinical atherosclerosis with MAFLD transitions according to its new definition has never been reported. METHODS: Using data from a community-based cohort, 6232 participants aged 40 years or older were included and were followed up for a median of 4.3 years during 2010-2015. Participants were categorized into four groups (stable non-MAFLD, MAFLD regressed to non-MAFLD, non-MAFLD progressed to MAFLD, and stable MAFLD). Subclinical atherosclerosis was defined as elevated carotid intima-media thickness (CIMT), elevated brachial-ankle pulse wave velocity (ba-PWV), or microalbuminuria. RESULTS: Compared with the stable non-MAFLD category, participants who progressed to MAFLD at follow-up visit had a 1.356-fold increased risk of developing elevated CIMT [odds ratio (OR) = 1.356; 95% confidence interval (CI) = 1.134-1.620], and a 1.458-fold increased risk of incident microalbuminuria (OR = 1.458; 95% CI = 1.034-2.056) after adjustment for confounders, respectively. In addition, participants with stable MAFLD showed 17.6%, 32.4%, and 35.4% increased risks of developing elevated CIMT, elevated ba-PWV and microalbuminuria, respectively. Compared with the stable MAFLD category, participants with MAFLD and low probability of fibrosis at baseline who regressed to non-MAFLD at follow-up visit had a 29.4% decreased risk of developing elevated CIMT (OR = 0.706; 95% CI = 0.507-0.984), a 43.1% decreased risk of developing elevated ba-PWV (OR = 0.569; 95% CI = 0.340-0.950), but was not significantly associated with incident microalbuminuria (OR = 0.709; 95% CI = 0.386-1.301). The decreased risks attributed to MAFLD regression were more evident in participants without diabetes or dyslipidemia, as well as in those with 0-1 metabolic risk abnormalities, respectively. CONCLUSIONS: MAFLD was significantly associated with higher risks of developing subclinical atherosclerosis. Moreover, the regression of MAFLD might modify the risks of developing subclinical atherosclerosis, especially among those with low probability of fibrosis or less metabolic risk abnormalities. Since 40% of baseline participants with missing data on MAFLD measurement at follow-up were excluded, the conclusions should be speculated with caution.

2.
Aging (Albany NY) ; 13(7): 10075-10086, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33818417

RESUMO

OBJECTIVE: To examine the association between stage 1 hypertension defined by the 2017 American College of Cardiology and American Heart Association (ACC/AHA) guideline and risk of developing arterial stiffness. METHODS: During 2010-2015, 4595 adults aged ≥40 years without cardiovascular disease were followed up for a median of 4.3 years. BP levels at baseline were categorized into normal, elevated, stage 1 hypertension, and stage 2 hypertension. The development of arterial stiffness was defined as a normal brachial-ankle pulse wave velocity (ba-PWV) at baseline and an increased ba-PWV at follow-up. RESULTS: Compared with participants with normal BP, participants with stage 1 hypertension had a 1.48-fold increased risk of developing arterial stiffness [odds ratio (OR) =2.48; 95% confidence interval (CI) =1.59-3.85] after adjustment for cardiovascular risk factors. The association was more evident in adults aged 40-59 years (OR =4.08; 95% CI =2.06-8.08) than that in those aged ≥60 years (OR =1.47; 95% CI =0.81-2.67). A systolic BP 130~139 mmHg was significantly associated with arterial stiffness independent of diastolic BP (OR =2.90; 95% CI =1.86-4.52). Stage 1 hypertension either at baseline or at follow-up was associated with increased risks compared with normal BP at both baseline and follow-up. CONCLUSIONS: The 2017 ACC/AHA stage 1 hypertension was significantly associated with higher risks of arterial stiffness.

3.
J Am Soc Nephrol ; 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33788701

RESUMO

BACKGROUND: The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guideline used eGFR and urinary albumin-creatinine ratio (ACR) to categorize risks for CKD prognosis. The utility of KDIGO's stratification of major CVD risks and predictive ability beyond traditional CVD risk prediction scores are unknown. METHODS: To evaluate CVD risks on the basis of ACR and eGFR (individually, together, and in combination using the KDIGO risk categories) and with the atherosclerotic cardiovascular disease (ASCVD) score, we studied 115,366 participants in the China Cardiometabolic Disease and Cancer Cohort study. Participants (aged ≥40 years and without a history of cardiovascular disease) were examined prospectively for major CVD events, including nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death. RESULTS: During 415,111 person-years of follow-up, 2866 major CVD events occurred. Incidence rates and multivariable-adjusted hazard ratios of CVD events increased significantly across the KDIGO risk categories in ASCVD risk strata (all P values for log-rank test and most P values for trend in Cox regression analysis <0.01). Increases in c statistic for CVD risk prediction were 0.01 (0.01 to 0.02) in the overall study population and 0.03 (0.01 to 0.04) in participants with diabetes, after adding eGFR and log(ACR) to a model including the ASCVD risk score. In addition, adding eGFR and log(ACR) to a model with the ASCVD score resulted in significantly improved reclassification of CVD risks (net reclassification improvements, 4.78%; 95% confidence interval, 3.03% to 6.41%). CONCLUSIONS: Urinary ACR and eGFR (individually, together, and in combination using KDIGO risk categories) may be important nontraditional risk factors in stratifying and predicting major CVD events in the Chinese population.

4.
Int J Cardiol ; 332: 209-215, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33667580

RESUMO

BACKGROUND: Excessive adiposity in adulthood is positively associated with the risk of cardiovascular disease (CVD). However, it is less studied how the risk is separately explained by early adulthood weight and later weight change, especially in Asian ancestries. METHODS: This study included 121160 participants in a large population-based cohort in China. Body weight at 20 and 40 years of age wase self-reported. Information on CVD history was obtained through standard questionnaires. RESULTS: The odds ratios (ORs) were 1.20 (95% CI, 1.10-1.31) for coronary heart disease (CHD), 1.74 (95% CI, 1.36-2.22) for myocardial infarction (MI), 1.14 (95% CI, 0.99-1.32) for stroke and 1.21 (95% CI, 1.12-1.31) for total CVD among individuals with early overweight, and became more prominent for early obesity. Meanwhile, A moderate weight gain of 2.5 kg between early adulthood and midlife significantly increased the risk of CHD (OR: 1.18, 95% CI: 1.05-1.32), stroke (OR: 1.19, 95% CI: 1.03-1.38) and total CVD (OR: 1.15, 95% CI: 1.04-1.27), and the risk escalated with higher amounts of weight gain. Conversely, a weight loss of 2.5 kg conferred lower risk of CVD compared with a stable weight. In further cross-analysis, participants with early adulthood overweight or obesity and significant weight gain afterwards exhibited the greatest risk of CVD. CONCLUSIONS: High early adulthood BMI and subsequent weight gain had both independent and combined effect on the risk of CVD after midlife. Therefore, weight management should start before early adulthood, and emphasized throughout adulthood for CVD prevention.

5.
BMJ Open ; 11(3): e040890, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33658258

RESUMO

OBJECTIVE: We aimed to examine the associations of urinary albumin-to-creatinine ratio (ACR) levels with risks of subclinical atherosclerosis, cardiovascular events and all-cause deaths. METHODS: Data from a large population-based cohort were used, which included 9580 participants aged ≥40 years free from cardiovascular diseases. Carotid intima-media thickness, brachial-ankle pulse wave velocity and ankle-brachial index were measured at baseline to assess subclinical atherosclerosis. After a median of 4.53 years' follow-up, 486 cardiovascular events and 230 all-cause deaths were recorded. RESULTS: The urinary ACR levels were categorised into three groups. Compared with the normal group (0≤ACR <7.82 mg/g), people with low-grade albuminuria (7.82≤ACR <30 mg/g) and albuminuria (ACR ≥30 mg/g) had higher levels of subclinical atherosclerosis. In prospective analysis, people with low-grade albuminuria was not significantly associated with cardiovascular events (HR=1.18; 95% CI 0.95 to 1.46], whereas people with albuminuria had a 50% higher risk of cardiovascular events (HR=1.50; 95% CI 1.11 to 2.03). People with low-grade albuminuria and albuminuria had 43% (HR=1.43; 95% CI 1.05 to 1.93) and 87% (HR=1.87; 95% CI 1.24 to 2.81) higher risks of all-cause deaths during follow-up, respectively. In stratified analysis, the association of higher ACR with risks of cardiovascular events and all-cause deaths was stronger among individuals with concomitant subclinical atherosclerosis, the presence of diabetes and more cardiovascular risk factors, respectively. CONCLUSIONS: ACR levels were positively associated with subclinical atherosclerosis and predicted the risks of cardiovascular events and all-cause deaths. Evaluation of ACR levels should be integrated into risk stratification and prevention of cardiovascular events and all-cause deaths, especially among those with pre-existing subclinical atherosclerosis and cardiometabolic abnormalities.

6.
J Diabetes ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33710784

RESUMO

BACKGROUND: Parity, pregnancy loss, and breastfeeding duration were found to be associated with diabetes. However, the results are inconsistent. Also, no epidemiological studies have examined the association of these reproductive factors with diabetes in the same large population. We aim to investigate the associations between parity, pregnancy loss, breastfeeding duration, and the risk of maternal diabetes in middle-aged and elderly Chinese females. METHODS: We included 131 174 females aged ≥40 years from the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study). Multivariable linear regression and logistic regression were used to assess the association between parity, pregnancy loss, and breastfeeding duration and type 2 diabetes. RESULTS: The number of parities and breastfeeding duration were positively related to fasting plasma glucose, 2-hour postload glucose, glycosylated hemoglobin, and homeostatic model assessment of insulin resistance. Compared with those with one birth, nulliparous women or women with 2 or ≥3 births had a significantly increased risk of diabetes. The odds ratios (OR) and 95% confidence intervals (CI) were 1.27 (1.10-1.48), 1.17 (1.12-1.22), and 1.28 (1.21-1.35), respectively. Compared with women without pregnancy loss, those who underwent 2 (OR 1.09; 95% CI, 1.04-1.14) or ≥3 pregnancy losses (OR 1.11; 95% CI, 1.04-1.18) had an increased risk of diabetes. Moreover, women with a breastfeeding duration ≥0 to 6 months (OR 0.82; 95% CI, 0.75-0.90) and ≥6 to 12 months (OR 0.94; 95% CI, 0.89-0.99) had a significantly lower risk of diabetes. CONCLUSIONS: Nulliparous women or women with multiparity or more than one pregnancy loss have an increased risk of diabetes in later life, while women who breastfeed more than 0 to 12 months have a lower risk of diabetes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-33570562

RESUMO

CONTEXT: The body mass index (BMI) and waist circumference (WC) as diagnostic tools of obesity do not reflect the same level of fat mass and whether obesity leads to various effects on cardiometabolic risk factors among different racial/ethnic population is unknown. OBJECTIVE: The study aims to address the multicollinearity between BMI and WC by using the residual model approach, and to assess and compare the effects of obesity metrics on cardiometabolic risk factors among different races/ethnicities. DESIGN, SETTING AND PARTICIPANTS: Data from a nationally representative sample of Mainland Chinese adults collected in 2010, and data from the National Health and Nutrition Evaluation Survey (NHANES) 2005-2016 were used. By conducting a regression analysis between WC and BMI, the variation of BMI was removed from WC measures and residual of WC was obtained. The associations between obesity metrics and cardiometabolic risk factors were compared among different races/ethnicities by sex. RESULTS: The residual WC was significantly associated with all the cardiometabolic risk factors in Mainland Chinese, and most of the factors in Non-Hispanic White and Non-Hispanic Black adults, but not in the other races/ethnicities. The standardized regression coefficients of the associations between obesity metrics and cardiometabolic factors showed that the obesity metrics had greater impact on systolic blood pressure, diastolic blood pressure and triglyceride in Chinese adults than those of other racial/ethnic groups. CONCLUSIONS: Chinese adults are more susceptible to the effects of overall obesity and fat distribution on cardiometabolic risk factors than the other racial/ethnic population.

8.
Nutr Metab (Lond) ; 18(1): 21, 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33608033

RESUMO

CONTEXT: Body composition may explain partially why non-obese individuals still at the risk of developing non-alcoholic fatty liver disease (NAFLD). The ratio of fat mass to fat-free mass (FM/FFM) has been proposed to assess the combined effect of different body compositions. OBJECTIVE: We aimed to investigate the associations of FM/FFM ratio with the risk of developing NAFLD and fibrosis and to identify the potential mediators according to obesity status. METHODS: This cohort study comprised 3419 adults age ≥ 40 years and free of NAFLD at baseline. Body composition was measured by bioelectrical impedance analysis. NAFLD was ascertained by ultrasonography and fibrosis was assessed by non-invasive score systems. RESULTS: For each 1 standard deviation increment in FM/FFM ratio, the odds ratio for the risk of NAFLD was 1.55 (95% confidence interval [CI] 1.23-1.95) in non-obese men, 1.33 (95% CI 1.08-1.65) in obese men, 1.42 (95% CI 1.44-1.67) in non-obese women, and 1.29 (95% CI 1.12-1.50) in obese women. Similar associations were also found between FM/FFM ratio and NAFLD with fibrosis. Mediation analysis showed that insulin resistance, triglycerides, high-density lipoprotein cholesterol, white blood cells, and total cholesterol mediated the association of FM/FFM ratio with NAFLD risk in specific sex and obesity subgroups. CONCLUSIONS: The FM/FFM ratio significantly associated with the NAFLD and fibrosis risk in both non-obese and obese individuals. Different factors may mediate the association between body composition and NAFLD risk according to different obesity status.

9.
J Clin Hypertens (Greenwich) ; 23(4): 802-812, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33421316

RESUMO

Blood pressure (BP) variability may have its effect on the development of vascular disease. The authors aimed to examine the association between the visit-to-visit variability (VVV) of BP and arterial stiffness in Chinese adults. The authors included 1407 participants from a prospective cohort study of community residents who were ≥40 years, without a history of myocardial infarction or stroke, and with data at the baseline, the second and the third visits in 2008, 2009, and 2013. The VVV of BP was defined as the standard deviation (SD), the coefficient of variation (CV), the average successive variability (ASV), and the variability independent of the mean (VIM) in BP levels at the 3 visits. Arterial stiffness was measured by brachial-ankle pulse wave velocity (ba-PWV) at the 2nd and the 3rd visits. Levels of ba-PWV change and the occurrence of an elevated ba-PWV increased significantly in the highest tertile of VVV measures of systolic BP (SBP) and pulse pressure (PP) compared with the lowest tertile, respectively. The multivariable regression analysis revealed that VVV measures of SBP and PP were significantly associated with levels of ba-PWV change and the risks of developing an elevated ba-PWV. The odds ratios (ORs) and 95% confidence intervals (CIs) for the risk were 2.12 (1.57-3.12) and 1.92 (1.38-2.68) in participants with the highest versus the lowest tertile of SBP-SD and PP-SD, respectively. No significant association was found for diastolic BP variability measures. The increased long-term variabilities of SBP and PP were associated with an increased risk of arterial stiffness.

10.
Eur J Nutr ; 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33399975

RESUMO

PURPOSE: Whether the association between fruit and type 2 diabetes (T2D) is modified by the genetic predisposition of T2D was yet elucidated. The current study is meant to examine the gene-dietary fruit intake interactions in the risk of T2D and related glycemic traits. METHODS: We performed a cross-sectional study in 11,657 participants aged ≥ 40 years from a community-based population in Shanghai, China. Fruit intake information was collected by a validated food frequency questionnaire by asking the frequency of consumption of typical food items over the previous 12 months. T2D-genetic risk score (GRS) was constructed by 34 well established T2D common variants in East Asians. The risk of T2D, fasting, 2 h-postprandial plasma glucose, and glycated hemoglobin A1c associated with T2D-GRS and each individual single nucleotide polymorphisms (SNPs) were tested. RESULTS: The risk of T2D associated with each 1-point of T2D-GRS was gradually decreased from the lower fruit intake level (< 1 times/week) [the odds ratio (OR) and 95% confidence interval (CI) was 1.10 (1.07-1.13)], to higher levels (1-3 and > 3 times/week) [the corresponding ORs and 95% CIs were 1.08 (1.05-1.10) and 1.07 (1.05-1.08); P for interaction = 0.04]. Analyses for associations with fasting, 2 h-postprandial plasma glucose and glycated hemoglobin A1c demonstrated consistent tendencies (all P for interaction ≤ 0.03). The inverse associations of fruit intake with risk of T2D and glucose traits were more prominent in the higher T2D-GRS tertile. CONCLUSIONS: Fruit intakes interact with the genetic predisposition of T2D on the risk of diabetes and related glucose metabolic traits. Fruit intake alleviates the association between genetic predisposition of T2D and the risk of diabetes; the association of fruit intake with a lower risk of diabetes was more prominent in population with a stronger genetic predisposition of T2D.

11.
Carcinogenesis ; 42(4): 611-620, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33367557

RESUMO

Lysophosphatidic acid (LPA) and its G-protein-coupled receptors (Lpar1-Lpar6) mediate a plethora of activities associated with cancer growth and progression. However, there is no systematic study about whether and how LPA promotes esophageal squamous cell carcinoma (ESCC). Here, we show that autotaxin (ATX), a primary LPA-producing enzyme, is highly expressed in ESCC, and overexpressed ATX is associated with the poor outcome of ESCC patients. Meanwhile, the expression of Lpar1 was much higher in ESCC cells compared with Het-1a (human esophagus normal epithelial cells). Functional experiments showed that LPA remarkably increased the proliferation and migration of ESCC cells. Furthermore, Lpar1 knockdown abolished the effect of LPA on ESCC cell proliferation and migration. Mechanistic studies revealed that LPA promoted ESCC cell lines proliferation and migration through PI3K/Akt pathway. Treatment of KYSE30 cell xenografts with Lpar1 inhibitor BMS-986020 significantly repressed tumor growth. Our results shed light on the important role of LPA in ESCC, and Lpar1 might be a potential treatment target for ESCC.

12.
Diabetes Care ; 44(2): 499-510, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33355246

RESUMO

OBJECTIVE: Comprehensive assessment of serum bile acids (BAs) aberrations before diabetes onset remains inconclusive. We examined the association of serum BA profile and coregulation with the risk of developing type 2 diabetes mellitus (T2DM) among normoglycemic Chinese adults. RESEARCH DESIGN AND METHODS: We tested 23 serum BA species in subjects with incident diabetes (n = 1,707) and control subjects (n = 1,707) matched by propensity score (including age, sex, BMI, and fasting glucose) from the China Cardiometabolic Disease and Cancer Cohort (4C) Study, which was composed of 54,807 normoglycemic Chinese adults with a median follow-up of 3.03 years. Multivariable-adjusted odds ratios (ORs) for associations of BAs with T2DM were estimated using conditional logistic regression. RESULTS: In multivariable-adjusted logistic regression analysis, per SD increment of unconjugated primary and secondary BAs were inversely associated with incident diabetes, with an OR (95% CI) of 0.89 (0.83-0.96) for cholic acid, 0.90 (0.84-0.97) for chenodeoxycholic acid, and 0.90 (0.83-0.96) for deoxycholic acid (P < 0.05 and false discovery rate <0.05). On the other hand, conjugated primary BAs (glycocholic acid, taurocholic acid, glycochenodeoxycholic acid, taurochenodeoxycholic acid, and sulfated glycochenodeoxycholic acid) and secondary BA (tauroursodeoxycholic acid) were positively related with incident diabetes, with ORs ranging from 1.11 to 1.19 (95% CIs ranging between 1.05 and 1.28). In a fully adjusted model additionally adjusted for liver enzymes, HDL cholesterol, diet, 2-h postload glucose, HOMA-insulin resistance, and waist circumference, the risk estimates were similar. Differential correlation network analysis revealed that perturbations in intraclass (i.e., primary and secondary) and interclass (i.e., unconjugated and conjugated) BA coregulation preexisted before diabetes onset. CONCLUSIONS: These findings reveal novel changes in BAs exist before incident T2DM and support a potential role of BA metabolism in the pathogenesis of diabetes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33290034

RESUMO

To date, many methods have been developed for inducing tumor cell death, such as using chemical drugs and radiation. However, all of them have a common problem, a lack of mechanisms for precisely regulating the death of tumor cells. It often leads to nonspecific death and systemic side effects. Therefore, the efficacy and further application of these traditional methods are limited. In this paper, a logic AND-gated sonogene nanosystem was designed for precisely regulating the apoptosis of tumor cells. The running of this system required two essential parts, MscL I92L channel protein and ultrasound. Ultrasound could open the MscL I92L protein channel which when expressed on cells triggers the influx and outflux of small molecules through the channel. When the channel is kept open for a long time, Ca2+ influx becomes excessive which in turn activates the Ca2+ apoptosis pathway of cells. The expression of MscL I92L protein and the applying of ultrasound constituted the logic AND gate which could implement the precise regulation to apoptosis. This strategy would help reduce nonspecific triggers and side effects. In this system, cationic nanoliposomes were prepared as the carrier for effectively delivering MscL I92L plasmids to tumor cells in vivo. We investigated the apoptosis-promoting effect of this system in different tumor cell lines (HeLa, B16, and 4T1). The results demonstrated that the apoptosis rate was highest in the B16 cell line (the early apoptosis rate was 11.9% and the late apoptosis rate was 59.1%) when the cells were subjected to consistent ultrasound (6 MHz, 15 W) for 30 min. This logic AND-gated sonogene nanosystem is expected to provide a new strategy and development direction for tumor therapy.

14.
Int Heart J ; 61(6): 1107-1113, 2020 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-33191341

RESUMO

Dickkopp-3 (DKK3) has been identified to play a protection role against atherosclerosis. However, little is known about the relationship between serum DKK3 levels and subclinical coronary atherosclerosis. We aimed to investigate the association of serum DKK3 with coronary stenosis in an asymptomatic Chinese population. A total of 550 Chinese adults aged 40-60 years and without symptoms or histories of cardiovascular diseases were randomly selected to undergo coronary computed tomography angiography. We defined ≥ 50% luminal narrowing as significant coronary stenosis and measured serum DKK3 levels by an enzyme-linked immunosorbent assay (ELISA). Fifty-nine participants had significant coronary stenosis and 223 had < 50% coronary stenosis. Proportions of significant coronary stenosis were 13.7%, 11.4%, and 7.1% in DKK3 tertiles 1-3, respectively (Ptrend = 0.0427). In the univariable multinomial logistic regression model, a decreasing DKK3 tertile was associated with significant coronary stenosis with borderline significance (OR: 1.40; 95% confidence intervals (CI): 0.98-1.99, P = 0.0642). In the multivariable regression model, participants in the lowest DKK3 tertile were associated with a 1.42-fold increased risk of significant coronary stenosis than those in the highest DKK3 tertile (OR: 2.42; 95% CI: 1.10-5.33; P = 0.0279) after adjustment for conventional cardiovascular risk factors. In addition, associations between DKK3 and significant coronary stenosis were consistent among subgroups. However, no significant association was found between serum DKK3 levels and < 50% coronary stenosis. Therefore, we have added to the existing evidence that serum DKK3 is inversely associated with the risk of significant coronary stenosis in asymptomatic middle-aged Chinese.

15.
J Diabetes ; 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33135296

RESUMO

BACKGROUND: Age at menarche was reported to be associated with the risk of diabetes. However, the impact of ideal cardiovascular health metrics (ICVHMs) on the association between age at menarche and adulthood diabetes risk remains unclarified. METHODS: We included 121431 women from the nationwide, population-based cohort of the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) study. The diagnosis of diabetes was based on the oral glucose tolerance test (OGTT) and HbA1c measurement. Logistic regression and multiplicative interaction analysis were conducted to investigate the potential interaction effect between age at menarche and ICVHMs on the development of diabetes. RESULTS: The multivariable-adjusted odds ratios of diabetes across categories of age at menarche (<14, 14-17, and > 17years) were 1.22 (95%CI: 1.17, 1.28), 1.00 (reference), and 0.89 (95%CI: 0.85, 0.93), respectively. In subgroup analysis, significant interactions were detected between total cholesterol, blood pressure levels and age at menarche on the risk of diabetes (P for interaction = 0.0091 and 0.0019, respectively). The increased risk associated with age at menarche <14 years was observed in participants with 3 or fewer ICVHMs, but not in women with 4 or more ICVHMs (P for interaction = 0.0001). CONCLUSIONS: Age at menarche was inversely associated with the risk of diabetes in adulthood in Chinese women, and it appeared to be modified by the presence of ICVHMs. Further studies are needed to clarify the precise interrelationship and the generalizability of our results. This article is protected by copyright. All rights reserved.

16.
Metabolism ; 112: 154353, 2020 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-32916152

RESUMO

BACKGROUND: The transcription factor YY1 is an important regulator for metabolic homeostasis. Activating mutations in YY1 lead to tumorigenesis of pancreatic ß-cells, however, the physiological functions of YY1 in ß-cells are still unknown. Here, we investigated the effects of YY1 ablation on insulin secretion and glucose metabolism. METHODS: We established two models of ß-cell-specific YY1 knockout mice. The glucose metabolic phenotypes, ß-cell mass and ß-cell functions were analyzed in the mouse models. Transmission electron microscopy was used to detect the ultrastructure of ß-cells. The flow cytometry analysis, measurement of OCR and ROS were performed to investigate the mitochondrial function. Histological analysis, quantitative PCR and ChIP were performed to analyze the target genes of YY1 in ß-cells. RESULTS: Our results showed that loss of YY1 resulted in reduction of insulin production, ß-cell mass and glucose tolerance in mice. Ablation of YY1 led to defective ATP production and mitochondrial ROS accumulation in pancreatic ß-cells. The inactivation of YY1 impaired the activity of mitochondrial oxidative phosphorylation, induced mitochondrial dysfunction and diabetes in mouse models. CONCLUSION: Our findings demonstrate that the transcriptional activity of YY1 is essential for the maintenance of mitochondrial functions and insulin secretion in ß-cells.

17.
Front Oncol ; 10: 1384, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32974138

RESUMO

Background: Studies on the association between circulating insulin-like growth factor 1 (IGF1) and prognosis of breast cancer are limited. Whether this association is modified by insulin levels and clinical characteristics is unclear. Methods: Serum concentrations of IGF1 as well as IGF binding protein 3 (IGFBP3), IGF1/IGFBP3 ratio, insulin, and C-peptide were prospectively examined in 2,682 invasive breast cancer patients who received surgery in Ruijin Hospital, Shanghai, between 2012 and 2017. Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence associated with different levels of IGF1 and other biomarkers with multivariable adjustment. Results: Compared with patients with low IGF1, patients with high IGF1 had a significantly lower risk of all-cause mortality (HR, 0.53; 95% CI, 0.29-0.96) and a borderline lower risk of breast cancer-specific mortality (HR, 0.53; 95% CI, 0.27-1.02). The inverse association between IGF1 and all-cause mortality was consistent across stratification subgroups but was more pronounced among patients with high insulin (HR, 0.40; 95% CI, 0.18-0.89), were premenopausal (HR, 0.34; 95% CI, 0.12-0.97), with a tumor size >2 cm (HR, 0.35; 95% CI, 0.17-0.73), with positive lymph node (HR, 0.49; 95% CI, 0.25-0.98), and with a high Ki-67 level (HR, 0.49; 95% CI, 0.26-0.95) (all P for interaction >0.05). No significant associations were found for IGFBP3, IGF1/IGFBP3 ratio, insulin, and C-peptide levels with all-cause mortality, breast cancer-specific mortality, and breast cancer recurrence. Conclusion: Circulating IGF1 was inversely and independently associated with all-cause mortality in invasive breast cancer patients, and this association was consistent across clinical risk factors.

18.
Glob Heart ; 15(1): 59, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32923352

RESUMO

Aims: To examine whether electrocardiography (ECG) could provide additional values to the traditional risk factors for cardiovascular disease (CVD) risk prediction among different cardiovascular risk subgroups. Methods: A total of 7,872 community residents aged ≥40 years were followed up for a median of 4.5 years. A 12-lead resting ECG was examined for participants at baseline. CVD events including myocardial infarction, stroke and cardiovascular mortality were collected. Cox proportional hazards models were used and models of traditional risk factors with and without ECG were compared. Results: At baseline, 2,470 participants (31.3%) had ECG abnormalities. During follow-up, 464 participants developed CVD events. ECG abnormalities were associated with an increased risk of CVD after adjustment for the traditional risk factors in participants with a 10-year atherosclerotic CVD (ASCVD) risk ≥10% (hazard ratio, HR: 1.45; 95% confidence interval, CI: 1.11, 1.91). Adding ECG abnormalities to the traditional CVD risk factors improved reclassification for those who did not experience events [net reclassification index: 8.0% (95% CI: 2%, 19.5%)], discrimination (integrated discrimination improvement: 0.7% (95% CI: 0.1%, 1.9%), and calibration (goodness of fit P value from 0.600 to 0.873) in participants with a 10-year ASCVD risk ≥10%. However, no significant association and improvement were found in participants with a 10-year ASCVD risk <10%. Conclusions: ECG screening might provide a marginal improvement in CVD risk prediction in adults at high risk. However, ECG should not be recommended in adults at low risk.

19.
Liver Int ; 2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32840963

RESUMO

BACKGROUND & AIM: Low-grade albuminuria, as an early marker of endothelial dysfunction and kidney damage, has been recognized as a risk factor for metabolic disorders. Epidemiological studies manifesting the association of low-grade albuminuria with the risk of incident NAFLD and fibrosis were not available. We aimed to investigate the association of low-grade albuminuria with incident NAFLD and fibrosis by glycemic status. METHODS: A prospective population-based study was performed in 3308 participants without NAFLD at recruitment. Baseline urinary albumin excretion was obtained by a first-voided early morning spot urine sample. At follow-up visit, incident NAFLD was diagnosed by hepatic ultrasound after excluding alcohol abuse and other cause of hepatic diseases. Fatty liver index (FLI) was employed to reflect liver fat content. Liver fibrosis was evaluated by NAFLD fibrosis score (NFS), fibrosis-4 score (FIB-4) and Hepamet fibrosis score (HFS), respectively. RESULTS: After 4.3 years of follow-up, 622 (18.8%) were detected as incident NAFLD. Participants with low-grade albuminuria imposed a 40.4% [1.404 (1.112-1.772)] greater risk on incident NAFLD, and 52.0% [1.520 (1.141-2.026)], 87.4% [1.874 (1.291-2.720)] and 40.4% [1.404 (1.038-1.898)] higher risks on newly-onset higher values of FLI, NFS and FIB-4, respectively. The effect of low-grade albuminuria was stronger in the subgroup of non-diabetic population. CONCLUSIONS: Low-grade albuminuria was independently associated with incident NAFLD and a higher probability of fibrosis, especially among non-diabetic individuals.

20.
Sensors (Basel) ; 20(15)2020 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-32756365

RESUMO

Railway inspection has always been a critical task to guarantee the safety of the railway transportation. The development of deep learning technologies brings new breakthroughs in the accuracy and speed of image-based railway inspection application. In this work, a series of one-stage deep learning approaches, which are fast and accurate at the same time, are proposed to inspect the key components of railway track including rail, bolt, and clip. The inspection results show that the enhanced model, the second version of you only look once (YOLOv2), presents the best component detection performance with 93% mean average precision (mAP) at 35 image per second (IPS), whereas the feature pyramid network (FPN) based model provides a smaller mAP and much longer inference time. Besides, the detection performances of more deep learning approaches are evaluated under varying input sizes, where larger input size usually improves the detection accuracy but results in a longer inference time. Overall, the YOLO series models could achieve faster speed under the same detection accuracy.

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