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1.
Eur J Pharmacol ; 911: 174552, 2021 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-34627808

RESUMO

Diabetic kidney disease (DKD) is a severe complication of diabetes mellitus for which there is still no effective treatment. We previously showed that upregulation of thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of thioredoxin (TRX), accelerates the progression of DKD. In this study, we hypothesized whether verapamil, a calcium channel blocker and an established TXNIP inhibitor, might exert a renal-protective effect on DKD by regulating TXNIP expression. Herein, a systemic pharmacological network study was performed and multiple molecules and pathways targeted by verapamil on DKD were characterized. Furthermore, diabetic mice were induced by streptozotocin (STZ), and verapamil (100 mg/kg/day) or saline was intraperitoneally injected into the mice. After 16 weeks, mice were analyzed for blood glucose, blood pressure, and functional parameters followed by sacrifice and evaluation of renal tubular injury, alterations in TXNIP, apoptosis and fibrosis markers. Additionally, the effects of treatment with verapamil (50 µM, 100 µM, 150 µM) under high glucose conditions on the expression of TXNIP and signaling pathway components in proximal tubular epithelial cells (PTEC, HK-2 cells) were explored. According to these findings, we conclude that verapamil might serve as a potential agent for the prevention and treatment of DKD.

2.
Eur J Pharmacol ; 911: 174482, 2021 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-34481875

RESUMO

Berberine facilitates the production of glucagon-like peptide-1 (GLP-1) by intestinal L cells. Here, we aimed to reveal the mechanism of berberine facilitating the production of GLP-1 by intestinal L cells. In this study, we confirmed that the 100 mg/kg berberine daily through diet decreased the miR-106b expression and elevated the expressions of ß-catenin and T-cell factor 4 (TCF4) in colon tissues of high-fat diet mice; berberine decreased the concentrations of triglycerides, total cholesterol and the ratio of low-density lipoprotein cholesterol and high-density lipoprotein cholesterol in mouse serum samples; berberine decreased the blood glucose in the mouse tail vein blood and promoted GLP-1 production by intestinal L cells in mouse serum samples and elevated the GLP-1 expression in mouse colon tissues. Meanwhile, the mechanism analysis demonstrated that a dose of 100 µM berberine down-regulated the miR-106b expression by elevating the methylation levels of miR-106b in STC-1 cells and miR-106b bound to TCF4 in 293T cells. Moreover, the 100 mg/kg berberine daily through diet activated the ß-catenin/TCF4 signaling pathway by decreasing miR-106b, thereby facilitating GLP-1 production in intestinal L cells through the in vivo assays. Conclusively, our experimental data illustrated that berberine decreased miR-106b expression by increasing its methylation levels and then activated the ß-catenin/TCF4 signaling pathway, thereby facilitating GLP-1 production by intestinal L cells.

3.
Metabolism ; 124: 154874, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34517014

RESUMO

AIMS/HYPOTHESIS: We aimed to evaluate the effect of NAFLD on the risk of incident cardiovascular disease (CVD) and estimated glomerular filtration rate (eGFR)-based chronic kidney disease (CKD), and further test the joint effects and interactions between NAFLD status and individual metabolic element, as well as the total 'ABCs' metabolic goal achievement, on the CVD and CKD risk among 101,296 patients with prediabetes or diabetes from a prospective cohort study. METHODS: We conducted the study based on the China Cardiometabolic Disease and Cancer Cohort (4C) study, a large-scale, population-based prospective cohort. After excluding alcohol abuse and other cause of hepatic diseases, we used fatty liver index (FLI) ≥ 60 as a proxy of NAFLD and stratified the probability of fibrosis by aspartate transaminase/alanine transaminase ratio (AAR) with cut-offs of 0.8 and 1.4. 'ABCs' metabolic goal was defined as subjects who had HbA1c < 6.5% (A), SBP/DBP < 130/80 mmHg (B), and LDL-C < 100 mg/dL (C). During 3.8 years follow-up, we validated 2340 CVD events based on medical records and identified 1943 participants developed CKD based on centrally tested eGFR. RESULTS: The multivariable adjusted hazard ratios (HRs) were 1.15 (95% confidence interval (CI), 1.05-1.27) for CVD events and 1.33 (95% CI, 1.20-1.48) for CKD among NAFLD patients, compared with participants without NAFLD. Of NAFLD patients, relative to individuals with low AAR (<0.8), those with high AAR (≥1.4) were more likely to experience CVD events [1.62 (1.21-2.18)] and CKD [1.63 (1.17-2.28)]. Participants with NAFLD and comorbid poorly controlled metabolic risk factors had higher risk of CVD events or CKD than having either alone, with a significant interaction between poor glycemic control and NAFLD on the risk of vascular complications. CONCLUSIONS: NAFLD was associated with incident CVD and CKD among patients with prediabetes or diabetes. Such associations were substantially modified by the comprehensive achievement of metabolic goal.

4.
Diabetes Res Clin Pract ; 180: 109039, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34481909

RESUMO

AIMS: This study aimed to assess the effects of the hemoglobin glycation index (HGI) on hyperglycemia diagnosis and summarize the general characteristics of patients with a high-HGI phenotype. METHODS: The fasting plasma glucose and glycated hemoglobin (HbA1c) levels of participants (n = 47,648) were used to estimate a linear regression equation and determine the baseline HGI. Overall, 42,317 participants without a history of diabetes were included in the final analysis. The participants were divided into three groups according to the tertiles (low, moderate, and high) of baseline HGI. Proportions and variables were compared among the three HGI groups. A multivariate ordered logistic regression model was used to explore associations between related variables and the high-HGI phenotype. RESULTS: Regression analysis indicated that the high-HGI phenotype was positively associated with female sex, advanced age, obesity, increased low-density lipoprotein and triglyceride levels, decreased high-density lipoprotein cholesterol, and postprandial glycemic excursion levels (all P < 0.05). The prevalence of hyperglycemia increased from the low- to the high-HGI groups when using HbA1c for diagnosis. CONCLUSIONS: Individuals with high HGI have similar clinical characteristics. Measuring HbA1c alone for diagnosis could lead to inappropriate diabetes management decisions in people with low or high HGI.

5.
J Diabetes ; 2021 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-34427386

RESUMO

BACKGROUND: Gestational hyperglycemia increases the risk of diabetes in later life. However, the risk of future cardiovascular diseases (CVD) related to gestational hyperglycemia remains inconclusive. The purpose of this study was to investigate the impact of gestational hyperglycemia on the subsequent risk of CVD and its modifying factors among elderly Chinese women. METHODS: We conducted a case-control study of elderly women from the baseline survey of Risk Evaluation of cAncers in Chinese diabeTic Individuals: a lONgitudinal (REACTION) study. Women with gestational hyperglycemia (n = 82), and controls matched by age and study site (n = 410) were included. Information on CVD, including reported coronary heart disease, stroke, or myocardial infarction, was collected through an interviewer-assisted questionnaire. RESULTS: Women with gestational hyperglycemia were more likely to develop diabetes (odds ratio [OR], 2.51; 95% confidence interval [CI], 1.50-4.18) and CVD (OR, 1.98; 95% CI, 1.05-3.74). Even without progressing to type 2 diabetes, gestational hyperglycemia was associated with an increased risk of CVD (OR, 2.88; 95% CI, 1.18-7.00). However, subgroup analysis indicated that compared with those without gestational hyperglycemia or hypertension, women with both gestational hyperglycemia and hypertension had higher risk of CVD (OR, 3.98; 95% CI, 1.65-9.58), whereas the risk estimate did not significantly change in women with gestational hyperglycemia alone (OR, 2.15; 95% CI, 0.71-6.57). Stratified analysis indicated that among those with overweight/obesity, inactive physical activity, or unhealthy dietary habits, gestational hyperglycemia increased the risk of CVD. CONCLUSIONS: In elderly Chinese women, gestational hyperglycemia was associated with an increased risk of CVD in later life. This association was independent of the progression to diabetes and might be modified by lifestyle factors and hypertension.

6.
Lab Invest ; 101(11): 1484-1493, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34446806

RESUMO

Leydig cells (LCs) apoptosis is responsible for the deficiency of serum testosterone in Late-onset hypogonadism (LOH), while its specific mechanism is still unknown. This study focuses on the role of long noncoding RNA (lncRNA) MIR22HG in LC apoptosis and aims to elaborate its regulatory mechanism. MIR22HG was up-regulated in the testicular tissues of mice with LOH and H2O2-treated TM3 cells (mouse Leydig cell line). Interference of MIR22HG ameliorated cell apoptosis and upregulated miR-125a-5p expression in H2O2-treated TM3 cells. Then, the interaction between MIR22HG and miR-125a-5p was confirmed with RIP and RNA pull-down assay. Further study showed that miR-125a-5p downregulated N-Myc downstream-regulated gene 2 (NDRG2) expression by targeting its 3'-UTR of mRNA. What's more, MIR22HG overexpression aggravated cell apoptosis and reduced testosterone production in TM3 cells via miR-125a-5p/NDRG2 pathway. MIR22HG knockdown elevated testosterone levels in LOH mice. In conclusion, MIR22HG up-regulated NDRG2 expression through targeting miR-125a-5p, thus promoting LC apoptosis in LOH.

7.
Endocrinol Metab (Seoul) ; 36(4): 778-789, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34372624

RESUMO

BACKGROUND: Subclinical hypothyroidism (SCH) is the most common thyroid dysfunction, and its relationship with blood pressure (BP) has been controversial. The aim of the study was to analyze the association between SCH and newly-diagnosed hypertension. METHODS: Based on data from the Thyroid disease, Iodine nutrition and Diabetes Epidemiology (TIDE) study, 49,433 euthyroid individuals and 7,719 SCH patients aged ≥18 years were enrolled. Patients with a history of hypertension or thyroid disease were excluded. SCH was determined by manufacturer reference range. Overall hypertension and stage 1 and 2 hypertension were diagnosed according to the guidelines issued by the American College of Cardiology/American Heart Association in 2017. RESULTS: The prevalence of overall hypertension (48.7%), including stage 1 (28.9%) and 2 (19.8%) hypertension, increased significantly in SCH patients compared with euthyroid subjects. With elevated serum thyroid stimulating hormone (TSH) level, the hypertension prevalence also increased significantly from the euthyroid to different SCH subgroups, which was more profound in females or subjects aged <65 years. The age- and sex-specific regression analysis further demonstrated the same trends in the general population and in the 1:1 propensity matched population. Similarly, several BP components (i.e., systolic, diastolic, and mean arterial BP) were positively associated with TSH elevation, and regression analysis also confirmed that all BP components were closely related with SCH in female subjects aged <65 years. CONCLUSION: The prevalence of hypertension increases for patients with SCH. SCH tends to be associated with hypertension and BP components in females younger than 65 years.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34427675

RESUMO

OBJECTIVES: To investigate the associations between individual and combined cardiometabolic morbidities and incident cardiovascular events in Chinese adults. DESIGN: A prospective, nationwide, and population-based cohort study. PARTICIPANTS: 133572 participants aged ≥ 40 years were included in the study. MAIN OUTCOME MEASURES: Cardiovascular disease (CVD) events. RESULTS: Compared with participants without diabetes, hypertension and dyslipidemia, participants with only diabetes (hazard ratio [HR], 1.58; 95% confidence interval [CI], 1.32-1.90) or only hypertension (2.04; 1.82-2.28) exhibited significantly higher risk for CVD events, while participants with only dyslipidemia (0.97; 0.84-1.12) exhibited no significantly higher risk for CVD events. When analyzed collectively, participants with diabetes plus hypertension (HR, 2.67; 95%CI, 2.33-3.06), diabetes plus dyslipidemia (1.57; 1.32-1.87), and hypertension plus dyslipidemia (2.12; 1.88-2.39) exhibited significantly higher risk for CVD. Moreover, participants with the combination of diabetes, hypertension and dyslipidemia exhibited the highest risk for CVD events (HR, 3.06; 95%CI, 2.71-3.46). Multivariable-adjusted HRs (95% CIs) for CVD associated with diabetes based on fasting glucose ≥7.0 mmol/L, oral glucose tolerance test-2h glucose ≥11.1 mmol/L, and hemoglobin A1c ≥6.5% were 1.64 (1.51-1.78), 1.57 (1.45-1.69), and 1.54 (1.42-1.66), respectively; associated with hypertension based on systolic blood pressure ≥140 mmHg and diastolic blood pressure ≥90 mmHg were 1.89 (1.76-2.03) and 1.74 (1.60-1.88), respectively; associated with dyslipidemia based on total cholesterol ≥6.22 mmol/L, low-density lipoprotein cholesterol ≥4.14 mmol/L, high-density lipoprotein cholesterol <1.04 mmol/L, and triglycerides ≥2.26 mmol/L were 1.18 (1.08-1.30), 1.30 (1.17-1.44), 1.00 (0.92-1.09), and 1.10 (1.01-1.20), respectively. CONCLUSIONS: Diabetes, hypertension and dyslipidemia showed additive associations with the risk of CVD events in middle-aged and elderly Chinese adults.

9.
Diabetes Obes Metab ; 23(11): 2551-2560, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34322974

RESUMO

AIMS: The aims of this study were to evaluate the associations of metabolic abnormalities with incident diabetic kidney disease (DKD) and to explore whether dyslipidaemia, particularly high fasting triglyceride (TG), was associated with the development of DKD. METHODS: In total, 11 142 patients with new-onset type 2 diabetes with baseline estimated glomerular filtration rates (eGFR) ≥60 mL/min/1.73 m2 were followed up during 2011-2016. Incident DKD was defined as eGFR <60 mL/min/1.73 m2 at follow-up. Multiple logistic regression analysis was conducted to explore the relationship of metabolic abnormalities at baseline and at follow-up with risks of DKD. High TG was defined by TG ≥1.70 mmol/L. Low high-density lipoprotein cholesterol (HDL-c) was defined by HDL-c <1.0 mmol/L for men or <1.3 mmol/L for women. RESULTS: Participants who developed DKD had higher levels of waist circumference and systolic blood pressure, and lower levels of HDL-c at both baseline and follow-up visits. The DKD group also had higher levels of post-load plasma glucose and TG at follow-up. Multivariate logistic regression analysis revealed that both high TG at baseline [odds ratio (OR) = 1.37, p = .012) and high TG at follow-up (OR = 1.71, p < .001) were significantly associated with increased risks of DKD. Patients with high TG levels at both baseline and follow-up had higher risk of DKD compared with constantly normal TG (OR = 1.65, p < .001) after adjustment for covariates. CONCLUSIONS: In a large population of patients with new-onset type 2 diabetes, a high TG level was an independent risk factor for the development of DKD. Tight TG control might delay the occurrence of DKD.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Neoplasias , China/epidemiologia , HDL-Colesterol , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/epidemiologia , Feminino , Humanos , Masculino , Fatores de Risco , Triglicerídeos
10.
Aging (Albany NY) ; 13(14): 18287-18297, 2021 07 28.
Artigo em Inglês | MEDLINE | ID: mdl-34319254

RESUMO

BACKGROUND: To explore the effect of albiflorin (AL) on streptozotocin (STZ)-induced Alzheimer's disease (AD) in rats. METHODS: A mouse model of diabetic encephalopathy was established by intraperitoneal injection of 1%STZ. Step down test and water maze test were used to test the cognitive function of rats. Congo Red Staining was used to detect the distribution of Aß plaques in the hippocampus of rats. Cytokine levels in serum and hippocampus were measured using ELISA. Serum insulin, oral glucose tolerance (OGTT), serum superoxide dismutase (SOD) activity and malondialdehyde (MDA) content were measured by commercial kits. And the content of Nrf-2/HO-1/HMGB1/NF-kB in the hippocampus of diabetic rats were detected by western blot. RESULTS AND CONCLUSION: Compared with the STZ model group, the average escape latency of rats in the AL group in the Morris water maze test was significantly shortened, and the average number of platform crossings and the ratio of distance/total swimming distance in the target quadrant were increased significantly. Staining of tissue sections and ELISA showed a decrease in Aß plaque density in the hippocampus of rats in the AL group. And serum insulin levels of rats in the ALgroup were significantly reduced and OGTT was improved. In addition, AL could also regulate the Nrf-2/HO-1/HMGB1/NF-kB signal pathway in the hippocampus. Therefore, AL may ameliorate STZ-induced cognitive impairment in rats by regulating oxidative stress and inflammation in the brain.

11.
Cell Tissue Res ; 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34278519

RESUMO

This study aimed to investigate the role of lncRNA FENDRR in apoptosis of Leydig cells and the further mechanism. The apoptosis of Leydig cells (TM3 cell line) was induced by H2O2-treatment and detected by flow cytometry. The function of FENDRR was determined by in vitro and in vivo silencing experiments. The mechanism of FENDRR in regulating the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was assessed by RNA immunoprecipitation, RNA pull-down, and ubiquitination assays. FENDRR expression was up-regulated in H2O2-treated TM3 cells. Knockdown of FENDRR augmented Nrf2 and HO-1 protein levels and testosterone production in H2O2-treated TM3 cells, whereas the apoptosis rate and caspase 3 activity were decreased. Mechanically, FENDRR bound to Nrf2 and promoted its ubiquitination and degradation. Nrf2 overexpression reversed the effects FENDRR overexpression on apoptosis, caspase 3 activity, and testosterone concentration in H2O2-treated TM3 cells. The in vivo experiments showed that FENDRR silence increased serum testosterone level and improved testosterone-related anti-depression behaviors of late-onset hypogonadism (LOH) mice. Our findings suggested that FENDRR could promote apoptosis of Leydig cells in LOH partly through facilitating Nrf2 degradation.

12.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(7): 659-662, 2021 Jul 10.
Artigo em Chinês | MEDLINE | ID: mdl-34247372

RESUMO

OBJECTIVE: To analyze the prenatal diagnosis, parental verification and pregnancy outcome of 6 fetuses with 22q11.2 microdeletion syndrome. METHODS: Copy number variation sequencing (CNV-seq)and chromosomal microarray analysis (CMA) were carried out for the fetuses. RESULTS: The fetuses were found to harbor 2.54-3.2 Mb microdeletions of the 22q11.2 region, among which one was maternally inherited and one was paternally inherited. Two parents opted to continue with the pregnancy, and 4 chose induced labor. One fetus was found to have tetralogy of Fallot, while two carrier parents and one fetus appeared to have normal phenotype. CONCLUSION: 22q11.2 microdeletions identified upon prenatal diagnosis should be treated carefully, with ultrasonic scan and parental verification taken into account.


Assuntos
Variações do Número de Cópias de DNA , Diagnóstico Pré-Natal , Feminino , Feto , Humanos , Análise em Microsséries , Gravidez , Resultado da Gravidez , Ultrassonografia Pré-Natal
13.
J Diabetes ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34259386

RESUMO

BACKGROUND: Type 2 diabetes is increasingly diagnosed at a younger age worldwide and in China. Limited data are available regarding the association between age at diabetes diagnosis and risks of albuminuria. This study sought to examine the independent effect of age at diagnosis of type 2 diabetes on the risk of albuminuria. METHODS: We used data from a nationwide multicenter study with 207 961 participants in mainland China. Age, sex, and study site were matched for 31 366 screen-detected type 2 diabetes cases and 31 366 normal controls. Age, sex, study site, and diabetes duration were matched for 7490 self-reported type 2 diabetes cases and 7490 normal controls. Risks of having albuminuria in matched type 2 diabetes vs controls were examined using multivariable logistic regression analysis in strata of age at diabetes diagnosis. RESULTS: Although the absolute rate of albuminuria is higher in older adults, the odds ratio of albuminuria in type 2 diabetes vs matched controls decreased with increasing age at diagnosis. For participants with diabetes diagnosed at an age of <50, 50 to 59, 60 to 69, or ≥70 years, the multivariable adjusted risk of albuminuria increased by 81%, 60%, 45%, and 33% for screen-detected diabetes, and 135%, 121%, 90%, and 58% for self-reported diabetes compared with their normal controls, respectively. CONCLUSIONS: A younger age at diagnosis of type 2 diabetes is associated with a more significantly elevated risk of albuminuria than an older age at diagnosis in Chinese adults.

14.
Diabetes Metab Syndr Obes ; 14: 2415-2425, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093028

RESUMO

Background: Lipid accumulation product (LAP) as a powerful marker of visceral obesity is an independent risk factor of chronic kidney disease. The present study attempted to explore the association between LAP and albuminuria in prediabetic individuals. Methods: We conducted a cross-sectional study and enrolled 26,529 participants with prediabetes over 40 years old with prediabetes from seven provinces in China. LAP was calculated from waist circumference and fasting triglycerides. Elevated albuminuria was defined by urinary albumin-creatinine ratio (uACR) ≥30 mg/g. Propensity score matching was applied to reduce bias, comparison between LAP and other traditional visceral obesity indices was performed and multiple logistic regression models were conducted to assess the association between LAP and albuminuria in the prediabetic population. Results: Individuals with uACR ≥30 mg/g were older and had higher BP, BMI, WC, TG, fasting insulin, glycohemoglobin and LAP, as well as lower eGFR and HDL level. Multiple logistic regression analysis showed elevated LAP was associated with increased odds of albuminuria (OR [95%CI]Q2 vs Q1 1.09 [0.94, 1.27], OR [95%CI]Q3 vs Q1 1.13 [0.97, 1.31], OR [95%CI]Q4 vs Q1 1.42 [1.21, 1.67], P for trend=0.018), and superior over waist-to-hip ratio or waist-to-height ratio. Stratification indicated that the prediabetic population with higher LAP level and characterized by female gender, middle age, being overweight, and rise in blood pressure were more likely to have increased uACR. Conclusion: Elevated level of LAP was associated with increased albuminuria in the prediabetic population in China.

15.
Front Endocrinol (Lausanne) ; 12: 651534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34122333

RESUMO

Background: Universal salt iodization (USI) was implemented in mainland China in 1996. The prevalence of hyperthyroidism and its risk factors now require examination. Methods: Data were acquired from a nationwide Thyroid, Iodine, and Diabetes Epidemiological survey (TIDE 2015-2017) of 78,470 subjects from 31 provinces. Iodine status, and thyroid hormones and antibodies were measured. Results: After two decades of USI, the prevalence of overt hyperthyroidism (OH), Graves' disease (GD), severe subclinical hyperthyroidism (severe SCH), and mild subclinical hyperthyroidism (mild SCH) in mainland China was 0.78%, 0.53%, 0.22%, and 0.22%, respectively. OH and GD prevalence were higher in women than in men (OH: 1.16% vs. 0.64%, P<0.001; GD: 0.65% vs. 0.37%, P<0.001).Prevalence was significantly decreased after 60 years-of-age compared with 30-39 years-of-age (OH:0.61% vs. 0.81%, P<0.001; GD: 0.38% vs. 0.57%, P<0.001).Excessive iodine(EI) and deficient iodine(DI) were both related to increased prevalence of OH (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.68-2.59; OR1.35, 95%CI 1.07-1.72, respectively); however, only deficient iodine was associated with increased prevalence of GD (OR1.67, 95%CI 1.30-2.15). Increased thyroid peroxidase antibody and thyroglobulin antibody levels were significantly associated with prevalence of OH and GD, but not severe SCH and mild SCH. Although hyperthyroidism was more prevalent in women, the association disappeared after adjusting for other factors such as antibody levels. Conclusion: OH and GD prevalences in mainland China are stable after two decades of USI. Iodine deficiency, elevated thyroid antibody levels, and middle age are the main risk factors for OH and GD. The severe SCH population, rather than the mild SCH population, shows similar characteristics to the OH population.

16.
J Leukoc Biol ; 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-34062006

RESUMO

Diabetic nephropathy (DN) is a leading cause of end-stage renal failure. The study aimed to investigate whether long noncoding RNA taurine-upregulated gene 1 (TUG1) can ameliorate the endoplasmic reticulum stress (ERS) and apoptosis of renal tubular epithelial cells in DN, and the underlying mechanism. The DN mouse model was established by streptozocin injection, and the human renal tubular epithelial cell line HK-2 was treated with high glucose (HG) to mimic DN in vitro. The molecular mechanism was explored through dual-luciferase activity assay, RNA pull-down assay, RNA immunoprecipitation (RIP), and chromatin immunoprecipitation (CHIP) assay. The expression of TUG1 was significantly decreased in the renal tubules of DN model mice. Overexpression of TUG1 reduced the levels of ERS markers and apoptosis markers by inhibiting reticulon-1 (RTN1) expression in HG-induced HK-2 cells. Furthermore, TUG1 down-regulated RTN1 expression by inhibiting the binding of transcription factor PU.1 to the RTN1 promoter, thereby reducing the levels of ERS markers and apoptosis markers. Meanwhile, TUG1-overexpression adenovirus plasmids injection significantly alleviated tubular lesions, and reduced RTN1 expression, ERS markers and apoptosis markers, whereas these results were reversed by injection of PU.1-overexpression adenovirus plasmids. TUG1 restrains the ERS and apoptosis of renal tubular epithelial cells and ameliorates DN through inhibition of transcription factor PU.1.

18.
J Diabetes ; 13(11): 857-867, 2021 Nov.
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.

19.
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.

20.
Int J Cardiol ; 332: 209-215, 2021 06 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.


Assuntos
Doenças Cardiovasculares , Adulto , Índice de Massa Corporal , Peso Corporal , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , China/epidemiologia , Humanos , Fatores de Risco
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