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1.
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.

2.
BMJ Open ; 11(1): e040214, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402405

RESUMO

OBJECTIVE: The relationship between obesity and albuminuria has not been clarified. This study aimed to investigate the correlation between obesity and the urinary albumin-creatinine ratio (UACR) in Southern and Northern China. DESIGN: A descriptive, cross-sectional study. SETTING: Eight regional centres in REACTION (China's Risk Evaluation of cAncers in Chinese diabeTic Individuals, a lONgitudinal study), including Dalian, Lanzhou, Zhengzhou, Guangzhou, Guangxi, Luzhou, Shanghai and Wuhan. PARTICIPANTS: A total of 41 085 patients who were not diagnosed with chronic kidney disease (CKD) and had good compliance were selected according to the inclusion criteria. Patients who were diagnosed with CKD, who had other kidney diseases that could lead to increased urinary protein excretion, who were using angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers and whose important data were missing were excluded. RESULTS: Participants with both, central and peripheral obesity, had a higher risk of elevated UACR, even after adjusting for multiple factors (OR: 1.14, 95% CI: 1.07 to 1.12, p<0.001), and the risk of high UACR in the South was more prominent than that in the North (OR South: 1.22, 95% CI: 1.11 to 1.34; OR North: 1.13, 95% CI: 1.04 to 1.22, p<0.001). The risk was also elevated in the male population, hypertensive individuals, glycosylated haemoglobin (HbA1c)≥6.5% and age ≥60 years in the South. Besides the above groups, diabetes was also a risk factor for the Northern population. CONCLUSIONS: In China, people with both central and peripheral obesity are prone to a high UACR, and the southern population has a higher risk than northern population. Factors such as male sex, hypertension, HbA1c≥6.5% and an age ≥60 years are also risk factors for CKD.

3.
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.

4.
Liver Int ; 41(1): 101-109, 2021 Jan.
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 glycaemia 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.

5.
J Steroid Biochem Mol Biol ; 206: 105788, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33227378

RESUMO

Congenital lipoid adrenal hyperplasia (LCAH), as the most severe form of congenital adrenal hyperplasia (CAH), is caused by mutations in the steroidogenic acute regulatory protein (STAR). Affected patients were typically characterized by adrenal insufficiency in the first year of life and present with female external genitalia regardless of karyotype. Non-classic LCAH patients usually present from 2 to 4 years old with glucocorticoid deficiency and mild mineralocorticoid deficiency, even develop naturally masculinized external genitalia at birth when they have 46,XY karyotype. We described thirty patients from unrelated Chinese families, including three non-classic LCAH ones. Four novel mutations were reported, including c.556A > G, c.179-15G > T, c.695delG and c.306 + 3_c.306 + 6delAAGT. The c.772C > T is the most common STAR mutation in Chinese population, suggesting a possibility of founder effect. Enzymatic activity assay combined with clinical characteristics showed a good genotype-phenotype correlation in this study. Residual STAR activity more than 20 % may be correlated with non-classic LCAH phenotype. We support the perspective that onset age may be affected by multiple factors and masculinization should be the main weighting factor for diagnosis of non-classic LCAH. Compared with 46,XX LCAH patients, less 46,XY ones were found in our report. A less comprehensive inspection and an easy diagnosis due to classical phenotype both would reduce the possibility of 46,XY LCAH patients to be referred to specialists or geneticists.

7.
Cardiovasc Diabetol ; 19(1): 209, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33302966

RESUMO

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates cholesterol metabolism by targeting the low-density lipoprotein receptor. Recent studies have shown that circulating PCSK9 is associated with glucose homeostasis and insulin resistance. The aim of this study was to examine the association of circulating PCSK9 levels and risk for the development of type 2 diabetes in individuals with prediabetes. METHODS: A population-based prospective study was conducted among 4205 Chinese subjects with prediabetes (average age 56.1 ± 7.5 years). Incident type 2 diabetes was diagnosed according to 2010 American Diabetes Association criteria. Circulating PCSK9 levels were measured using a commercially available enzyme-linked immunosorbent assay (ELISA). The association of circulating PCSK9 levels with the risk of incident type 2 diabetes was assessed by Cox regression analysis. RESULTS: During a median follow-up period of 3.1 years, 568 subjects developed type 2 diabetes. Baseline circulating PCSK9 levels were significantly higher in female subjects developing incident type 2 diabetes than in those not developing incident type 2 diabetes (p < 0.001). In female subjects, the risk of incident type 2 diabetes was significantly higher in the highest PCSK9 quartile group (hazard ratio 2.16; 95% confidence interval 1.16-4.04) than in the lowest quartile group after adjustments for age, body mass index, waist circumference, C-reactive protein, γ-glutamyltransferase, triglycerides, low-density lipoprotein cholesterol, systolic blood pressure, and homeostatic model assessment of insulin resistance score. No significant association was observed between PCSK9 and incident type 2 diabetes in male subjects. CONCLUSION: Elevated circulating PCSK9 levels are associated with an increased incidence of type 2 diabetes in female subjects with prediabetes.

8.
Diabetes Care ; 2020 Dec 18.
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.

10.
Diabetes Ther ; 2020 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-33216280

RESUMO

INTRODUCTION: East Asians are more susceptible to early-onset diabetes than Europeans and exhibit reduced insulin secretion at earlier stages. PAX4 plays a critical role in the development of ß-cells. The dysfunction-missense variants PAX4 R192H and PAX4 R192S are common in East Asians but rare in Europeans. Therefore, we aim to investigate the diabetes-associated genes, including PAX4 R192H/S, in East Asians with early-onset diabetes. METHODS: Exome variants of 80 Chinese early-onset diabetes patients (onset age < 35 years) after the exclusion of type 1 diabetes (T1D) were detected by a customized gene panel covering 32 known diabetes-associated genes. Then, 229 subjects with early-onset diabetes (T1D excluded) and 1679 controls from the Chinese population were genotyped to validate the association of PAX4 R192H/S with early-onset diabetes and related phenotypes. RESULTS: The gene panel detected 11 monogenic diabetes patients with five novel mutations among the 80 early-onset diabetes patients. Asian-specifically enriched PAX4 R192H and R192S were associated with early-onset diabetes (R192H: OR 1.88, 95% CI 1.37-2.60, P = 8.41 × 10-5; R192S: OR 1.71, 95% CI 1.17-2.51, P = 0.005). In early-onset diabetes patients, PAX4 R192H carriers had higher haemoglobin A1c (HbA1c) levels (P = 0.030) and lower 2 h C-peptide levels in the oral glucose tolerance test (OGTT) (P = 0.040); R192S carriers had lower fasting C-peptide (FCP) (P = 0.011) and 2 h C-peptide levels (P = 0.033) in OGTT than non-variant carriers. CONCLUSIONS: The ethnic-specific enrichment of PAX4 R192H/S predisposing East Asians to early-onset diabetes with decreased C-peptide levels may be one explanation of the discrepancy of diabetes between East Asians and Europeans. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT01938365).

11.
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.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/sangue , Doenças Assintomáticas/epidemiologia , Doença da Artéria Coronariana/sangue , Estenose Coronária/sangue , Adulto , China/epidemiologia , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Estenose Coronária/diagnóstico por imagem , Estenose Coronária/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fatores de Risco , Índice de Gravidade de Doença
12.
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 was unclear. METHODS: We included 121 431 women from the nationwide, population-based cohort of the REACTION study (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 glycosylated hemoglobin (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 > 17 years) were 1.22 (95% confidence interval [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 regarding the risk of diabetes (P for interaction = .0091 and .0019, respectively). The increased risk associated with age at menarche <14 years was observed in participants with three or fewer ICVHMs, but not in women with four or more ICVHMs (P for interaction = .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.

13.
J Diabetes ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33200507

RESUMO

BACKGROUND: Several studies have suggested that nonalcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD). The excretion of low-level albuminuria (LLA) elevates as the prevalence of CVD increases. However, few studies have explored the association between NAFLD and LLA. METHODS: This cross-sectional study included 31 147 Chinese adults (7664 men and 23 483 women). The "normal" level of albuminuria as determined by the urinary albumin to creatinine ratio (UACR) was below 30 mg/g. LLA was defined as a higher level within the "normal" albuminuria range (5.54 mg/g < LLA≤29.9 mg/g). The participants with NAFLD were defined as having a fatty liver index (FLI) ≥ 60. The FLI was calculated using the Bedogni equation. RESULTS: A positive association was found between UACR and FLI through multivariate linear regression analyses (nonstandardized ß ± SE: .047 ± 0.004, P <.001). The logistic regression analyses revealed that NAFLD had adjusted odds ratios (ORs) showing a significant relationship with LLA in models 1 to 4 (all subjects: OR, 1.207; 95% CI, 1.098-1.326; women: OR, 1.43; 95% CI, 1.26-1.63; all P <.001); however, we did not find significant adjusted ORs among the men. In the stratified analyses, the relationship between NAFLD and LLA was significant among postmenopausal women with a body mass index ≥24 but <28 kg/m2 , fasting plasma glucose ≥5.6 but <7.0 mmol/L, or postprandial plasma glucose ≥7.8 but <11.1 mmol/L and those aged below 60 years without moderate-intensity exercise. CONCLUSIONS: A noteworthy association between NAFLD and LLA was found among postmenopausal women who had borderline blood glucose values, were overweight, and did not engage in moderate-intensity physical activity.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33120423

RESUMO

CONTEXT: The mTORC1 is crucial for beta cell identity and function in rodents. However, its possible relevance to physiopathology of diabetes in human remains unclear. OBJECTIVE: To understand the participation of mTORC1 in human beta cells in prediabetes and diabetes. DESIGN: We evaluated the PS6 immunofluorescence intensity in islets of pancreatic sections from 12 non-diabetic (ND), 11 impaired fasting glucose (IFG) and 11 glycemic-controlled type 2 diabetic (T2D) subjects. We also assessed the dynamic change of mTORC1 activity in beta cells of db/db mice with newly onset of diabetes. RESULTS: There exists inter-cellular heterogeneity of mTORC1 activities in human islet. Islet mTORC1 activity was independently and positively correlated with FBG in ND, but not in IFG and T2D. Moreover, we did not detect significant change in mTORC1 activities between T2D and ND. Of note, the islet mTORC1 activities were significantly higher in IFG than in ND. We further stratified IFG according to their islet PS6 levels and found that IFG-PS6 high exhibited remarkably higher Ucn3 and Glut2 expression in their beta cells compared to IFG-PS6 low. Consistently, we also detected a significant increase in mTORC1 activities in prediabetic db/db mice, compared to non-diabetic littermates. Interestingly, mTORC1 activities determined beta cell adaptation or failure in db/db mice: a strong negative correlation was found between islet mTORC1 activities and fasting glucose levels in db/db mice during their progression to diabetes. CONCLUSIONS: Our finding highlights a dynamic islet mTORC1 response in beta cell adaption/failure in human T2D.

15.
Nat Commun ; 11(1): 5015, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-33024120

RESUMO

Human gut microbiome is a promising target for managing type 2 diabetes (T2D). Measures altering gut microbiota like oral intake of probiotics or berberine (BBR), a bacteriostatic agent, merit metabolic homoeostasis. We hence conducted a randomized, double-blind, placebo-controlled trial with newly diagnosed T2D patients from 20 centres in China. Four-hundred-nine eligible participants were enroled, randomly assigned (1:1:1:1) and completed a 12-week treatment of either BBR-alone, probiotics+BBR, probiotics-alone, or placebo, after a one-week run-in of gentamycin pretreatment. The changes in glycated haemoglobin, as the primary outcome, in the probiotics+BBR (least-squares mean [95% CI], -1.04[-1.19, -0.89]%) and BBR-alone group (-0.99[-1.16, -0.83]%) were significantly greater than that in the placebo and probiotics-alone groups (-0.59[-0.75, -0.44]%, -0.53[-0.68, -0.37]%, P < 0.001). BBR treatment induced more gastrointestinal side effects. Further metagenomics and metabolomic studies found that the hypoglycaemic effect of BBR is mediated by the inhibition of DCA biotransformation by Ruminococcus bromii. Therefore, our study reports a human microbial related mechanism underlying the antidiabetic effect of BBR on T2D. (Clinicaltrial.gov Identifier: NCT02861261).


Assuntos
Berberina/farmacologia , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Probióticos/uso terapêutico , Berberina/uso terapêutico , Feminino , Microbioma Gastrointestinal/fisiologia , Hemoglobina A Glicada/metabolismo , Humanos , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Masculino , Metagenoma/efeitos dos fármacos , Metagenoma/genética , Pessoa de Meia-Idade , Placebos , Resultado do Tratamento
16.
Diabetes Metab Res Rev ; : e3416, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33120435

RESUMO

Patients with type 2 diabetes mellitus (T2DM) are at risk of developing atherosclerotic cardiovascular disease (ASCVD) and chronic kidney disease (CKD), which are important causes of disabling and death in patients with T2DM. For the prevention and management of ASCVD or CKD, cardiovascular risk factors should be systematically evaluated, and ASCVD and CKD should be screened in patients with T2DM. In this consensus, we recommended that metformin should be used as the first-line therapy for patients with T2DM and ASCVD or very high cardiovascular risk, heart failure (HF) or CKD, and should be retained in the treatment regimen unless contraindicated or not tolerated. In patients with T2DM and established ASCVD or very high cardiovascular risk, addition of a glucagon-like peptide 1 receptor agonist (GLP-1RA) or sodium-glucose cotransporter type 2 (SGLT2) inhibitor with proven cardiovascular benefits should be considered independent of individualised glycated haemoglobin (HbA1C ) targets. In patients with T2DM and HF, an SGLT2 inhibitor should be preferably added regardless of HbA1C levels. In patients with T2DM and CKD, SGLT2 inhibitors should be preferred for the combination therapy independent of individualised HbA1C targets, and GLP-1RAs with proven renal benefits would be alternative if SGLT2 inhibitors are contraindicated. Moreover, the prevention of hypoglycaemia and management of multiple risk factors by comprehensive regimen, including lifestyle intervention, antihypertensive therapies, lipid-lowering treatment and antiplatelet therapies, should be kept in mind in treating patients with T2DM and ASCVD, HF or CKD.

17.
Artigo em Inglês | MEDLINE | ID: mdl-33087340

RESUMO

INTRODUCTION: Early screening for diabetic retinopathy (DR) with an efficient and scalable method is highly needed to reduce blindness, due to the growing epidemic of diabetes. The aim of the study was to validate an artificial intelligence-enabled DR screening and to investigate the prevalence of DR in adult patients with diabetes in China. RESEARCH DESIGN AND METHODS: The study was prospectively conducted at 155 diabetes centers in China. A non-mydriatic, macula-centered fundus photograph per eye was collected and graded through a deep learning (DL)-based, five-stage DR classification. Images from a randomly selected one-third of participants were used for the DL algorithm validation. RESULTS: In total, 47 269 patients (mean (SD) age, 54.29 (11.60) years) were enrolled. 15 805 randomly selected participants were reviewed by a panel of specialists for DL algorithm validation. The DR grading algorithms had a 83.3% (95% CI: 81.9% to 84.6%) sensitivity and a 92.5% (95% CI: 92.1% to 92.9%) specificity to detect referable DR. The five-stage DR classification performance (concordance: 83.0%) is comparable to the interobserver variability of specialists (concordance: 84.3%). The estimated prevalence in patients with diabetes detected by DL algorithm for any DR, referable DR and vision-threatening DR were 28.8% (95% CI: 28.4% to 29.3%), 24.4% (95% CI: 24.0% to 24.8%) and 10.8% (95% CI: 10.5% to 11.1%), respectively. The prevalence was higher in female, elderly, longer diabetes duration and higher glycated hemoglobin groups. CONCLUSION: This study performed, a nationwide, multicenter, DL-based DR screening and the results indicated the importance and feasibility of DR screening in clinical practice with this system deployed at diabetes centers. TRIAL REGISTRATION NUMBER: NCT04240652.

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.
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.

20.
J Clin Endocrinol Metab ; 105(11)2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32785672

RESUMO

OBJECTIVE: Pancreatic neuroendocrine tumors (pNETs) causing ectopic adrenal corticotropic hormone (ACTH) syndrome (EAS) are rare and aggressive with little known information. We aimed to elucidate the clinical features and molecular mechanisms of pNETs with EAS by methylation analysis. METHODS: Seven patients with ectopic ACTH-secreting pNETs who were diagnosed at Shanghai Clinical Endocrine and Metabolic Diseases Center and Pancreatic Disease Center in Ruijin Hospital between 2001 and 2019 were enrolled. Twenty patients with ectopic ACTH-secreting thymic neuroendocrine tumors (TNETs) and 7 with nonfunctional pNETs (nf-pNETs) were also enrolled as controls. We collected clinical data and measured POMC promoter CpG methylation. RESULTS: All 7 patients had elevated ACTH and urinary free cortisol (UFC) levels with positive ACTH staining in the pancreas and were diagnosed with ectopic ACTH-secreting pNET. Of the 7 patients, 6 underwent surgery and 1 underwent transarterial embolization (TAE). Two patients were free of disease after surgery; 2 died within 90 days after surgery; and 3 had metastases and died within 1 year. Compared with ACTH-secreting TNETs, ACTH-secreting pNETs had similar clinical and biochemical features but a significantly poorer prognosis. POMC promoter CpG methylation was significantly lower in ACTH-secreting pNETs than in nf-pNETs and normal pancreas. CONCLUSIONS: ACTH-secreting pNETs are aggressive and fatal. Surgery is definitively curative for patients with resectable primary tumors without metastasis. Pro-opiomelanocortin (POMC) promoter hypomethylation caused pNETs to produce ACTH. This study further supplements the genetic features of ACTH-secreting NETs.

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