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1.
J Steroid Biochem Mol Biol ; 225: 106192, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36167262

RESUMO

Diagnosis of nonclassic adrenal hyperplasia (NCAH) due to 21-hydroxylase deficiency (21-OHD) may be challenging due to its occult manifestations. To characterize clinical and molecular features of NCAH patients due to 21-hydroxylase deficiency, we retrospectively included 78 NCAH patients. Their phenotype and genotype were presented and compared. The transcription activities of novel CYP21A2 promoter variants were investigated using a dual-reporter luciferase assay system. This cohort included 53 females (68 %) and 25 males (32 %). The median of onset age was 13 years old (female: 13 range from 7 to 38; male: 11 range from 6 to 71). Menstrual cycle disorder was the most common complaint in females (62 %, n = 33) and for males, it was adrenal incidentalomas (52 %, n = 13). A total of 17 (22 %) patients complained of infertility. The most frequently variant was p.Ile173Asn (20 %, n = 31). Importantly, five variants in the promoter region including - 103/- 126 and - 196/- 296 were found in 21 (27 %) patients. Patients with promoter variants showed older onset age and less impaired hormone levels of 17-hydroxyprogesterone, ACTH, progesterone, and androstenedione. Compared with the wild-type promoter, the basic transcription activity of - 103/- 126 and - 196/- 296 promoter variants were reduced by 57% and 25%, respectively. Therefore, females with menstrual cycle disorders or infertility and males with adrenal incidentaloma should be considered of NCAH due to 21-OHD. When genotyping patients with NCAH, the promoter region of the CYP21A2 gene should be also investigated.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hiperplasia Suprarrenal Congênita , Infertilidade , Masculino , Feminino , Humanos , Neoplasias das Glândulas Suprarrenais/genética , Estudos Retrospectivos , Hiperplasia , Hiperplasia Suprarrenal Congênita/genética , Hiperplasia Suprarrenal Congênita/diagnóstico , Esteroide 21-Hidroxilase/genética
2.
Hypertension ; 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36353998

RESUMO

BACKGROUND: Education, intelligence, and cognition are associated with hypertension, but which one plays the most prominent role in the pathogenesis of hypertension and which modifiable risk factors mediate the causal effects remains unknown. METHODS: Using summary statistics of genome-wide association studies of predominantly European ancestry, we conducted 2-sample multivariable Mendelian randomization to estimate the independent effects of education, intelligence, or cognition on hypertension (FinnGen study, 70 651 cases/223 663 controls; UK Biobank, 77 723 cases/330 366 controls) and blood pressure (International Consortium of Blood Pressure, 757 601 participants), and used 2-step Mendelian randomization to evaluate 25 potential mediators of the association and calculate the mediated proportions. RESULTS: Meta-analysis of inverse variance weighted Mendelian randomization results from FinnGen and UK Biobank showed that genetically predicted 1-SD (4.2 years) higher education was associated with 44% (95% CI: 0.40-0.79) decreased hypertension risk and 1.682 mm Hg lower systolic and 0.898 mm Hg lower diastolic blood pressure, independently of intelligence and cognition. While the causal effects of intelligence and cognition on hypertension were not independent of education, 6 out of 25 cardiometabolic risk factors were identified as mediators of the association between education and hypertension, ranked by mediated proportions, including body mass index (mediated proportion: 30.1%), waist-to-hip ratio (22.8%), body fat percentage (14.1%), major depression (7.0%), high-density lipoprotein cholesterol (4.7%), and triglycerides (3.4%). These results were robust to sensitivity analyses. CONCLUSIONS: Our findings illustrated the causal, independent impact of education on hypertension and blood pressure and outlined cardiometabolic mediators as priority targets for prevention of hypertension attributable to low education.

3.
J Clin Med ; 11(22)2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36431325

RESUMO

PURPOSE: Transsphenoidal surgery is the first-line treatment for Cushing's disease (CD), even with negative preoperative magnetic resonance imaging (MRI) results. Some patients with persistent or recurring hypercortisolism have negative MRI findings after the initial surgery. We aimed to analyze the efficacy of repeat surgery in two groups of patients and determine if there is an association between positive MRI findings and early remission. PATIENTS AND METHODS: Clinical, imaging, and biochemical information of 42 patients who underwent repeat surgery by a single neurosurgeon between 2002 and 2021 was retrospectively analyzed. We compared the endocrinological, histopathological, and surgical outcomes before and after repeat surgery among 14 CD patients with negative MRI findings and 28 patients with positive MRI findings. RESULTS: Immediate remission was achieved in 29 patients (69.0%) who underwent repeat surgery. Among all patients, 28 (66.7%) had MRI findings consistent with solid lesions. There was no significant difference in remission rates between the recurrence and persistence groups (77.8% vs. 57.1%, odds ratio = 2.625, 95% confidence interval = 0.651 to 10.586). Patients in remission after repeat surgery were not associated with positive MRI findings (odds ratio = 3.667, 95% confidence interval = 0.920 to 14.622). CONCLUSIONS: In terms of recurrence, repeat surgery in patients with either positive or negative MRI findings showed reasonable remission rates. For persistent disease with positive MRI findings, repeat surgery is still an option; however, more solid evidence is needed to determine if negative MRI findings are predictors for failed reoperations for persistent hypercortisolism.

4.
J Diabetes ; 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36446626

RESUMO

BACKGROUND: The association between the Chinese Visceral Adiposity Index (CVAI) and urinary albumin to creatinine ratio (UACR) has not been illustrated. The current study aimed to investigate the association between CVAI and UACR and to compare the discriminative power of CVAI, triglyceride, body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) with UACR in the Chinese community population. METHODS: This study included 34 732 participants from the REACTION (Risk Evaluation of cAncers in Chinese diabeTic Individuals) study. Binary logistic regression analyses were performed to detect the association between CVAI, triglyceride, BMI, WC, WHR and UACR. RESULTS: Binary logistic regression analysis showed that, after adjusting for potential confounders, in women, CVAI (odds ratio [OR]:1.16, 95% confidence interval [CI]: 1.01-1.34) and triglyceride (OR: 1.18, 95% CI: 1.04-1.33) were associated with UACR, whereas BMI, WC, and WHR were not associated with UACR; in men, CVAI (OR: 1.24, 95% CI: 1.02-1.50), WC (OR: 1.21, 95% CI 1.00-1.48), and triglycerides (OR: 1.18, 95% CI 0.97-1.44) were associated with UACR, whereas BMI and WHR were not associated with UACR. Stratified analysis showed that the correlation between CVAI and UACR was stronger in the population with 5.6 ≤ fasting blood glucose (FBG) <7.0 or 7.8 ≤ post-load blood glucose (PBG) <11.1 mmol/L, FBG ≥7.0 or PBG ≥11.1, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg. CONCLUSIONS: In the Chinese general population, CVAI and UACR were significantly associated in both genders. At higher CVAI levels, the population with prediabetes, diabetes, and hypertension has a more significant association between CVAI and UACR.

5.
Front Endocrinol (Lausanne) ; 13: 1018657, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36387870

RESUMO

Objectives: Recent studies found that secreted protein acidic and rich in cysteine-like protein 1 (Sparcl1) could inhibit lipid droplets accumulation by peroxisome proliferator-activated receptor-gamma (PPARγ) signal pathway. However, the associations of serum Sparcl1 level with lipids profiles and other metabolic phenotypes remain unknown in human population study. Methods: We determined serum Sparcl1 using sandwich enzyme-linked immunosorbent assays among 1750 adults aged 40 years and older from a community in Shanghai, China. Generalized linear regression models were used to evaluate the association between Sparcl1 and metabolic measures. Multivariable-adjusted logistic regression analyses were performed to evaluate the relationship of serum Sparcl1 with prevalent dyslipidemia. Results: With the increment of serum Sparcl1, participants tended to have lower level of triglycerides, and higher level of high-density lipoprotein cholesterol (all P for trend < 0.01). No significant associations between serum Sparcl1 and glucose, blood pressure, or body size were observed. The generalized linear regression models suggested that per standard deviation (SD) increment of serum Sparcl1 was significantly inversely associated with triglycerides (ß= -0.06, P=0.02). The prevalence of dyslipidemia decreased across the sparcl1 quartiles (P for trend <0.01). After controlling the potential confounders, participants in the highest quartile of sparcl1 concentration had the lowest prevalence of dyslipidemia (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.91), compared with the lowest quartile. Per SD increment of Sparcl1 was associated with 20% (OR, 0.80; 95%CI, 0.69-0.94) lower prevalence of hypertriglyceridemia and 12% (OR, 0.88; 95%CI, 0.79-0.97) lower prevalence of dyslipidemia. The association between serum Sparcl1 and dyslipidemia were generally consistent across subgroups (all P for interaction > 0.05). Conclusion: Serum Sparcl1 was significantly associated with decreased risk of prevalent dyslipidemia in Chinese population. Further studies are warranted to confirm this association.


Assuntos
Proteínas de Ligação ao Cálcio , Dislipidemias , Proteínas da Matriz Extracelular , Adulto , Humanos , Pessoa de Meia-Idade , China/epidemiologia , Dislipidemias/epidemiologia , Triglicerídeos , Proteínas de Ligação ao Cálcio/sangue , Proteínas da Matriz Extracelular/sangue
6.
Diabetologia ; 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36372821

RESUMO

AIMS/HYPOTHESIS: Exposure to artificial light at night (LAN) disrupts the circadian timing system and might be a risk factor for diabetes. Our aim was to estimate the associations of chronic exposure to outdoor LAN with glucose homoeostasis markers and diabetes prevalence based on a national and cross-sectional survey of the general population in China. METHODS: The China Noncommunicable Disease Surveillance Study was a nationally representative study of 98,658 participants aged ≥18 years who had been living in their current residence for at least 6 months recruited from 162 study sites across mainland China in 2010. Diabetes was defined according to ADA criteria. Outdoor LAN exposure in 2010 was estimated from satellite data and the participants attending each study site were assigned the same mean radiance of the outdoor LAN at the study site. The linear regression incorporating a restricted cubic spline function was used to explore the relationships between LAN exposure and markers of glucose homoeostasis. Cox regression with a constant for the time variable assigned to all individuals and with robust variance estimates was used to assess the associations between the levels of outdoor LAN exposure and the presence of diabetes by calculating the prevalence ratios (PRs) with adjustment for age, sex, education, smoking status, drinking status, physical activity, family history of diabetes, household income, urban/rural areas, taking antihypertensive medications, taking lipid-lowering medications, and BMI. RESULTS: The mean age of the study population was 42.7 years and 53,515 (weighted proportion 49.2%) participants were women. Outdoor LAN exposure levels were positively associated with HbA1c, fasting and 2 h glucose concentrations and HOMA-IR and negatively associated with HOMA-B. Diabetes prevalence was significantly associated with per-quintile LAN exposure (PR 1.07 [95% CI 1.02, 1.12]). The highest quintile of LAN exposure (median 69.1 nW cm-2 sr-1) was significantly associated with an increased prevalence of diabetes (PR 1.28 [95% CI 1.03, 1.60]) compared with the lowest quintile of exposure (median 1.0 nW cm-2 sr-1). CONCLUSIONS/INTERPRETATION: There were significant associations between chronic exposure to higher intensity of outdoor LAN with increased risk of impaired glucose homoeostasis and diabetes prevalence. Our findings contribute to the growing evidence that LAN is detrimental to health and point to outdoor LAN as a potential novel risk factor for diabetes.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36373429

RESUMO

CONTEXT: Whether diabetes diagnosed at different age groups is causally associated with cardiovascular diseases (CVDs) is unknown. OBJECTIVE: We conducted two-sample Mendelian randomization analyses to investigate the causal associations of diabetes by age at diagnosis with five type-specific CVDs and 11 cardiometabolic traits. METHODS: We selected 208 single nucleotide polymorphisms (SNPs) for diabetes and 3, 21, 57, and 14 SNPs for diabetes diagnosed at <50, 50-60, 60-70, and >70 years, respectively, based on the GWAS (24,986 cases/187,130 controls) in the UK Biobank, and extracted genetic associations with stroke, myocardial infarction, heart failure, atrial fibrillation, and CVD mortality, as well as blood pressures, adiposity measurements, and lipids and apolipoproteins from corresponding European-descent GWASs. The inverse-variance weighted method was used as main analysis with several sensitivity analyses. RESULTS: Diabetes diagnosed at all four age groups was causally associated with increased risks of stroke (5%-8%) and myocardial infarction (8%-10%), higher systolic blood pressure (0.56-0.94 mmHg) and waist-to-hip ratio (0.003-0.004), and lower body mass index (0.31-0.42 kg/m2), waist circumference (0.68-0.99 cm), and hip circumference (0.57-0.80 cm). Diabetes diagnosed at specific age groups was causally associated with increased risks of heart failure (4%) and CVD mortality (8%), higher diastolic blood pressure (0.20 mmHg) and triglycerides (0.06 SD), and lower high-density lipoprotein cholesterol (0.02 mmol/L). The effect sizes of genetically determined diabetes on CVD subtypes and cardiometabolic traits were comparable and the corresponding 95% confidence intervals largely overlapped across the four age groups. CONCLUSION: Our findings provide novel evidence that genetically determined diabetes subgroups by age at diagnosis have similar causal effects on CVD and cardiometabolic risks.

8.
BMC Public Health ; 22(1): 2078, 2022 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-36376828

RESUMO

BACKGROUND: Age has substantial influence on metabolic diseases patterns. Ethnic disparities of metabolic characteristics between Chinese and other populations also exist. Large-scale investigations of age-specific prevalence, subtypes and modifiable risk factors of metabolic disorders are essential to promote individualized strategies for the control and prevention of metabolic diseases in multi-ethnic populations. The study aims to address the age-specific prevalence, subtype characteristics and risk factor profiles of metabolic diseases among different races/ethnicities. METHODS: We analyzed data from the China Noncommunicable Disease Surveillance 2010 and the National Health and Nutrition Evaluation Survey (NHANES). We examined the prevalence and subtypes of hypertension, diabetes and hyperlipidemia across age groups in four ethnic populations. We also investigated the odds ratios (ORs) of metabolic diseases associated with 11 classical risk factors in the young and the elder Mainland Chinese. RESULTS: The sex and BMI standardized prevalence of hypertension in Chinese aged 18-40 years was 18.5% and was the highest among the four populations. The main pathophysiologic subtype of diabetes was characterized by insulin resistance, instead of ß-cell dysfunction in Mainland Chinese, and this pattern was more evident in obese subjects. The major subtype of hyperlipidemia in Mainland Chinese was hypertriglyceridemia, while Non-Hispanic Whites and Blacks were more prone to high low-density lipoprotein cholesterol. For risk of hypertension, diabetes and hyperlipidemia, young Chinese adults were more prone to general and central obesity than older ones. The other factors showed similar effects on the young and the old. CONCLUSIONS: The age-specific prevalence, subtypes and risk factors of metabolic diseases were substantially different in Chinese and other ethnic/racial populations.


Assuntos
Diabetes Mellitus , Hipertensão , Adulto , Humanos , Idoso , Prevalência , Inquéritos Nutricionais , Fatores de Risco , Obesidade/complicações , Diabetes Mellitus/epidemiologia , HDL-Colesterol , Hipertensão/epidemiologia , Hipertensão/complicações , Fatores Etários
10.
Eur J Nutr ; 2022 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-36261730

RESUMO

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.

11.
J Diabetes ; 14(11): 739-748, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36217863

RESUMO

BACKGROUND: Evidence regarding the impact of education on diabetes risk is scarce in developing countries. We aimed to explore the association between education and diabetes within a large population in China and to identify the possible mediators between them. METHODS: Information on educational level and lifestyle factors was collected through questionnaires. Diabetes was diagnosed from self-report and biochemical measurements. A structural equation model was constructed to quantify the mediation effect of each mediator. RESULTS: Compared with their least educated counterparts, men with college education had a higher risk of diabetes (odds ratio [OR] 1.19; 95% confidence interval [CI], 1.12-1.27), while college-educated women were less likely to have diabetes (OR 0.77; 95% CI, 0.73-0.82). Obesity was the strongest mediator in both genders (proportion of mediation: 11.6% in men and 23.9% in women), and its association with education was positive in men (ß[SE] 0.0387 [0.0037]) and negative in women (ß[SE] -0.0824 [0.0030]). Taken together, all behavioral factors explained 12.4% of the excess risk of diabetes in men and 33.3% in women. CONCLUSIONS: In a general Chinese population, the association between education level and diabetes was positive in men but negative in women. Obesity was the major mediator underlying the education disparities of diabetes risk, with a stronger mediation effect among women.


Assuntos
Diabetes Mellitus , Obesidade , Feminino , Humanos , Masculino , Fatores de Risco , Escolaridade , Obesidade/complicações , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/diagnóstico , China/epidemiologia
12.
Clin Immunol ; 245: 109160, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36270470

RESUMO

Three different subsets of circulating human monocytes, CD14++CD16- (classical), CD14++CD16+ (intermediate), and CD14+CD16+ (non-classical) monocytes, have been recently identified. New evidence suggests that levels of intermediate monocytes or CD16+ (intermediate and non-classical) monocytes are increased in autoimmune diseases. However, studies regarding the role of each monocyte subset in the pathogenesis of Graves' disease (GD) are lacking. We aimed to investigate the clinical implications of these subsets and their potential role in GD pathogenesis. CD14++CD16+ monocytes showed a more activated state in GD patients than other monocyte subpopulations. An increased proportion of circulating CD14++CD16+ monocytes and a decreased proportion of circulating CD14++CD16- monocytes in GD patients were detected, and CD14++CD16+ monocyte frequencies were positively correlated with GD clinical parameters. Additionally, a follow-up analysis indicated that the CD14++CD16- monocyte percentage increased and the CD14++CD16+ monocyte percentage decreased post-treatment. We found that CD14++CD16+ GD monocytes promoted the expansion of IFN-γ+CD4+ cells. The Th1-polarizing cytokine IL-12, secreted after direct contact with patient CD14++CD16+ monocytes and CD4+ T cells, was responsible for IFN-γ+CD4+ cell development. Our results suggest that CD14++CD16+ monocytes are involved in GD pathogenesis and the critical role of CD14++CD16+ monocytes in the generation of potentially pathogenic Th responses in GD.


Assuntos
Doença de Graves , Monócitos , Humanos , Células Th1 , Receptores de IgG , Receptores de Lipopolissacarídeos , Diferenciação Celular
13.
J Diabetes ; 14(9): 606-619, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36163589

RESUMO

BACKGROUND: The study aimed to explore the associations of nonalcoholic fatty liver disease (NAFLD) with the remission and progression along the glycemic continuum. METHODS: This prospective cohort study was performed among the general population in 2010-2015. NAFLD was defined as ultrasound-detected hepatic steatosis with absence of excessive alcohol consumption and other hepatic diseases. Remission of type 2 diabetes referred to glycated hemoglobin <6.5% without hypoglycemic agents for ≥3 months. Prediabetes remission referred to normalization of blood glucose. Multivariable logistic analysis was applied to identify the risk of glycemic metabolic transition. RESULTS: During a median follow-up of 4.3 years, participants with NAFLD had a significantly higher risk of progressing from normal glucose tolerance to diabetes (3.36 [1.60-7.07]) and lower likelihood of diabetes remission (0.48 [0.30-0.78]). Associations in participants with overweight or obesity and higher probability of hepatic fibrosis remained consistent. Results related to the effect of NAFLD on the specific glucose parameters were generally in line with the changes of glycemic status. NAFLD improvement decreased the risk of prediabetes progressing to diabetes (0.50 [0.32-0.80]) and increased the probability of prediabetes remission (2.67 [1.49-4.79]). NAFLD tended to show the most significant association with glycemic progression and decreased the likelihood in remission of prediabetes and diabetes. CONCLUSIONS: Presence of NAFLD increased risk of glycemic progression and decreased likelihood of remission. NAFLD improvement mitigated glycemic deterioration, whereas NAFLD progression impeded the chance of remission. The results emphasized joint management of NAFLD and diabetes and further focused on liver-specific subgroups of diabetes to tailor early intervention.


Assuntos
Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Estado Pré-Diabético , Glicemia , Hemoglobina A Glicada , Humanos , Hipoglicemiantes , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estado Pré-Diabético/epidemiologia , Estudos Prospectivos , Fatores de Risco
14.
Circ Cardiovasc Qual Outcomes ; 15(9): e008774, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-36065814

RESUMO

BACKGROUND: Many studies demonstrate a J-shaped association between blood pressure and cardiovascular diseases (CVDs), but the findings are plagued by confounding from other traditional cardiovascular risk factors (CVRFs). Our aims were to examine the associations of systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels with CVD in individuals without major CVRFs and whether there were thresholds for the association. METHODS: In the 4C study (China Cardiometabolic Disease and Cancer Cohort), 36 042 CVRF-free participants without CVD, diabetes, dyslipidemia, hypertension, or smoking were identified during 2011 to 2012. Among CVRF-free participants, 17 476 CVRF-preferable individuals with better glycemic (fasting glucose, <110 mg/dL; 2-hour post-load glucose, <140 mg/dL) and lipid profile (total cholesterol, <200 mg/dL; LDL [low-density lipoprotein] cholesterol, <130 mg/dL) were selected. The total person-years of follow-up for CVRF-free subjects and CVRF-preferable subjects were 130 147 and 63 573 person-years, respectively. Information on the development of major CVDs was collected during 2014 to 2016. Cox proportional hazard models were performed to estimate the risks for incident CVD by SBP and DBP groups, respectively. RESULTS: We found that both baseline SBP and DBP presented significantly linear associations with CVD risks in CVRF-free and CVRF-preferable participants. There is significant increase in the CVD risk among CVRF-free participants with baseline SBP level of 110 to 119 mm Hg (hazard ratio, 1.79 [95% CI, 1.19-2.71]), 120 to 129 mm Hg (hazard ratio, 2.03 [95% CI, 1.36-3.03]), and 130 to 139 mm Hg (hazard ratio, 2.15 [95% CI, 1.40-3.28]) compared with SBP <110 mm Hg. Significant increases were also observed for DBP level of 80 to 89 mm Hg (hazard ratio, 1.43 [95% CI, 1.03-1.97]) compared with DBP <70 mm Hg. Similar results were observed in CVRF-preferable participants. CONCLUSIONS: SBP and DBP with levels currently considered normal were significantly and linearly associated with incident CVD without thresholds above 110/70 mm Hg among Chinese adults without major CVRFs.


Assuntos
Doenças Cardiovasculares , Hipertensão , Adulto , Pressão Sanguínea , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/epidemiologia , LDL-Colesterol , Glucose , Humanos , Hipertensão/complicações , Hipertensão/diagnóstico , Hipertensão/epidemiologia , Fatores de Risco
15.
Diabetes Care ; 45(11): 2718-2728, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36161993

RESUMO

OBJECTIVE: To investigate the causal role of choline metabolites mediating sodium-glucose cotransporter 2 (SGLT2) inhibition in coronary artery disease (CAD) and type 2 diabetes (T2D) using Mendelian randomization (MR). RESEARCH DESIGN AND METHODS: A two-sample two-step MR was used to determine 1) causal effects of SGLT2 inhibition on CAD and T2D; 2) causal effects of three choline metabolites, total choline, phosphatidylcholine, and glycine, on CAD and T2D; and 3) mediation effects of these metabolites. Genetic proxies for SGLT2 inhibition were identified as variants in the SLC5A2 gene that were associated with both levels of gene expression and hemoglobin A1c. Summary statistics for metabolites were from UK Biobank, CAD from CARDIoGRAMplusC4D (Coronary ARtery DIsease Genome wide Replication and Meta-analysis [CARDIoGRAM] plus The Coronary Artery Disease [C4D] Genetics) consortium, and T2D from DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) and the FinnGen study. RESULTS: SGLT2 inhibition (per 1 SD, 6.75 mmol/mol [1.09%] lowering of HbA1c) was associated with lower risk of T2D and CAD (odds ratio [OR] 0.25 [95% CI 0.12, 0.54], and 0.51 [0.28, 0.94], respectively) and positively with total choline (ß 0.39 [95% CI 0.06, 0.72]), phosphatidylcholine (0.40 [0.13, 0.67]), and glycine (0.34 [0.05, 0.63]). Total choline (OR 0.78 [95% CI 0.68, 0.89]) and phosphatidylcholine (OR 0.81 [0.72, 0.91]) were associated with T2D but not with CAD, while glycine was associated with CAD (0.94 [0.91, 0.98]) but not with T2D. Mediation analysis showed evidence of indirect effect of SGLT2 inhibition on T2D through total choline (0.91 [0.83, 0.99]) and phosphatidylcholine (0.93 [0.87, 0.99]) with a mediated proportion of 8% and 5% of the total effect, respectively, and on CAD through glycine (0.98 [0.96, 1.00]) with a mediated proportion of 2%. The results were well validated in at least one independent data set. CONCLUSIONS: Our study identified the causal roles of SGLT2 inhibition in choline metabolites. SGLT2 inhibition may influence T2D and CAD through different choline metabolites.


Assuntos
Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Inibidores do Transportador 2 de Sódio-Glicose , Humanos , Colina , Doença da Artéria Coronariana/genética , Diabetes Mellitus Tipo 2/metabolismo , Estudo de Associação Genômica Ampla/métodos , Glicina/genética , Análise da Randomização Mendeliana/métodos , Fosfatidilcolinas , Polimorfismo de Nucleotídeo Único , Fatores de Risco , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico
16.
Front Oncol ; 12: 938123, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36172142

RESUMO

Objective: Our previous work found COX4I2 was associated with angiogenesis in pheochromocytoma. The purpose of this study was to explore the role of COX4I2 in regulating angiogenesis in pheochromocytoma. Methods: Distribution of COX4I2 was evaluated by scRNA-seq in one case of pheochromocytoma and the findings were verified by immunostaining. COX4I2 was further knocked down in target cells. Changes of angiogenesis-related genes were evaluated by qPCR in target cells. Results: The scRNA-seq revealed high mRNA expression of COX4I2 in fibroblasts rather than tumor cells. Immunostaining of COX4I2 confirmed its distribution in fibroblasts. Knocking down COX4I2 in NIH3T3 cell line led to significant reduction of angiogenesis-related genes, especially ANG1 and HGF. Conclusions: Fibroblasts mediate the angiogenesis of pheochromocytoma by increasing COX4I2 expression, possibly by affecting ANG1 and HGF.

17.
J Diabetes ; 14(9): 596-605, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36071605

RESUMO

BACKGROUND: The triglyceride glucose (TyG) index is closely associated with subclinical atherosclerosis. However, the association remains inconclusive among obese and nonobese individuals. METHODS: This prospective study was conducted in 5751 adults with normal carotid intima-media thickness (CIMT) at baseline. We divided the population into four groups based on the TyG index, which was calculated by the following formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Information on CIMT was acquired by ultrasonography. Incident elevated CIMT was defined as IMT values greater than 0.9 mm at follow-up. Odds ratios (ORs) and 95% confidence intervals (CIs) of the associations between TyG index and elevated CIMT were estimated using multivariable logistic regression models. RESULTS: After a median follow-up of 4.3 years, 722 (12.6%) individuals had progressed to elevated CIMT. Compared with the second quartile of the TyG index, the first and fourth quartile both conferred higher risks of elevated CIMT after adjusting for potential confounders. In the total population, the ORs for the first and fourth quartile were 1.29 (95% CI, 1.00-1.66) and 1.42 (95% CI, 1.11-1.83), respectively. Restricted cubic splines demonstrated an approximately U-shaped association between TyG index and elevated CIMT among the total and nonobese adults (P for nonlinearity <.05), but not in those with general or abdominal obesity. CONCLUSIONS: A U-shaped association was observed between TyG index and elevated CIMT only among nonobese Chinese adults.


Assuntos
Espessura Intima-Media Carotídea , Glucose , Adulto , Biomarcadores , Glicemia , Eletrólitos , Humanos , Obesidade/complicações , Estudos Prospectivos , Fatores de Risco , Triglicerídeos
18.
J Diabetes ; 14(10): 685-694, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36176175

RESUMO

BACKGROUND: Previous studies reported that famine exposure had an effect on metabolic syndrome (MetS). However, there is an inadequacy of study regarding the association between famine exposure, adulthood general obesity, and the risk of MetS. METHODS: A total of 8883 subjects aged ≥40 years from Jiading community in Shanghai were included. We defined famine exposure subgroups as nonexposed (1963-1974), fetal exposed (1959-1962), childhood exposed (1949-1958), and adolescence exposed (1941-1948). MetS was defined based on the National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATP III) criteria. RESULTS: Compared with the nonexposed group, the risks of MetS were increased in the fetal-, childhood-, and adolescence-exposed groups with odds ratios (OR) and 95% confidence intervals (CI) of 1.48 (1.23-1.78), 1.89 (1.63-2.20), and 2.34 (1.99-2.74), respectively. After adjusting for sex, age, smoking status, drinking status, education, body mass index (BMI), and physical activity, the increased risk of MetS related to the fetal-exposed and childhood-exposed groups with OR and 95% CI of 1.42 (1.04-1.94) and 1.50 (1.02-2.21), respectively, were observed only in women. Famine exposure was significantly associated with MetS among individuals with a BMI < 23 kg/m2 (p for interaction between BMI categories and famine exposure = 0.0002 in the whole cohort), while there existed a gender difference (p = 0.0023 in females, p = 0.4484 in males). When evaluating the joint effects of the combination of famine exposure in early life and general obesity in adulthood on MetS, we observed the highest estimate in participants with both adulthood general obesity and fetal famine exposure (OR 17.52; 95% CI, 10.07-30.48) compared with those without famine exposure nor adulthood obesity. CONCLUSIONS: Obesity in adulthood significantly further aggravated the risk of MetS in individuals who experienced early life undernutrition, especially in females.


Assuntos
Síndrome Metabólica , Efeitos Tardios da Exposição Pré-Natal , Inanição , Trifosfato de Adenosina , Adolescente , Adulto , Criança , China/epidemiologia , Fome Epidêmica , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/etiologia , Obesidade/complicações , Obesidade/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/etiologia , Fatores de Risco , Inanição/complicações , Inanição/epidemiologia
20.
Nat Immunol ; 23(10): 1484-1494, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36138182

RESUMO

The heterogeneous cellular microenvironment of human airway chronic inflammatory diseases, including chronic rhinosinusitis (CRS) and asthma, is still poorly understood. Here, we performed single-cell RNA sequencing (scRNA-seq) on the nasal mucosa of healthy individuals and patients with three subtypes of CRS and identified disease-specific cell subsets and molecules that specifically contribute to the pathogenesis of CRS subtypes. As such, ALOX15+ macrophages contributed to the type 2 immunity-driven pathogenesis of one subtype of CRS, eosinophilic CRS with nasal polyps (eCRSwNP), by secreting chemokines that recruited eosinophils, monocytes and T helper 2 (TH2) cells. An inhibitor of ALOX15 reduced the release of proinflammatory chemokines in human macrophages and inhibited the overactivation of type 2 immunity in a mouse model of eosinophilic rhinosinusitis. Our findings advance the understanding of the heterogeneous immune microenvironment and the pathogenesis of CRS subtypes and identify potential therapeutic approaches for the treatment of CRS and potentially other type 2 immunity-mediated diseases.


Assuntos
Pólipos Nasais , Rinite , Sinusite , Animais , Doença Crônica , Eosinófilos , Humanos , Camundongos , Mucosa Nasal
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