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1.
Liver Int ; 2023 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-36719063

RESUMO

BACKGROUND & AIMS: The causal association of lower birthweight with nonalcoholic fatty liver disease (NAFLD) and the mediating pathways remain unclear. We aimed to investigate the causal, independent association of lower birthweight with NAFLD and identify potential metabolic mediators and their mediation effects in this association. METHODS: We performed two-step, two-sample Mendelian randomization (MR) using genome-wide association study (GWAS) summary statistics for birthweight from Early Growth Genetics consortium of 298,142 Europeans, NAFLD from a GWAS meta-analysis of 8,434 NAFLD cases and 770,180 controls of Europeans, and 25 candidate mediators from corresponding reliable GWASs. RESULTS: Genetically determined each 1-SD lower birthweight was associated with a 45% (95% CI: 1.25-1.69) increased risk of NAFLD, and this causal association persisted after adjusting for childhood obesity or adult adiposity traits in multivariable MR. Two-step MR identified six out of 25 candidate mediators partially mediate the effect of lower birthweight on NAFLD, including fasting insulin (proportion mediated: 22.05%), leucine (17.29%), isoleucine (13.55%), valine (11.37%), alanine (10.01%), and monounsaturated fatty acids (MUFA; 7.23%). Bidirectional MR suggested a unidirectional effect of insulin resistance on isoleucine, leucine, and valine, and a unidirectional effect of alanine on insulin resistance. CONCLUSIONS: This MR study elucidated the causal impact of lower birthweight on subsequent risk of NAFLD, independently of later life adiposity, and identified mediators including insulin resistance, branched-chain amino acids, alanine, and MUFA in this association pathway. Our findings shed light on the pathogenesis of NAFLD and imply additional targets for prevention and intervention of NAFLD attributed to low birthweight.

2.
Diabetes Metab ; 49(2): 101420, 2023 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-36640827

RESUMO

AIM: We aimed to examine risks of major cardiovascular events (MACEs), renal outcomes, and all-cause mortality in type 2 diabetes mellitus (T2DM) patients with different diabetic kidney disease (DKD) subtypes. METHODS: A total of 36,509 participants with T2DM recruited from 20 community sites across mainland China were followed up during 2011-2016. DKD subtypes were categorized based on albuminuria (urinary albumin-to-creatinine ratio, UACR ≥ 30 mg/g) and reduced estimated glomerular filtration rate (eGFR < 60 ml/min/1.73 m2) as Alb-/eGFR-, Alb+/eGFR-, Alb-/eGFR+, and Alb+/eGFR+. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs) of developing clinical outcomes in DKD subtypes. RESULTS: More than half (53.5%) of participants with diabetes and reduced eGFR had normal UACR levels (Alb-/eGFR+), termed as non-albuminuria DKD. These patients had a modest increase in the risks of MACEs (hazard ratio, HR 1.42 [95% CI 1.08;1.88]) and mortality (HR 1.42 [1.04;1.92]) compared with patients without DKD, whereas CKD progression was not significantly increased (HR 0.97 [0.60;1.57]). Participants with albuminuria (Alb+/eGFR- or Alb+/eGFR+) had higher risks of clinical outcomes. Subgroup analysis revealed that the associations between non-albuminuria DKD and risks of MACEs and mortality were more evident in those aged <65 years. CONCLUSION: Non-albuminuria DKD accounts for more than half of DKD cases with low eGFR in Chinese diabetes patients. Diabetes patients with albuminuria are at higher risks of developing clinical outcomes and warrant early intervention, as well as patients with non-albuminuria DKD with age < 65 years.

3.
Hypertension ; 2023 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-36601917

RESUMO

BACKGROUND: High blood pressure (BP) is highly prevalent in patients with chronic kidney disease. However, the thresholds to initiate BP-lowering treatment in this population are unclear. We aimed to examine the associations between BP levels and clinical outcomes and provide evidence on potential thresholds to initiate BP-lowering therapy in people with chronic kidney disease. METHODS: This nationwide, multicenter, prospective cohort study included 12 523 chronic kidney disease participants without antihypertensive therapy in mainland China. Participants were followed up during 2011 to 2016 for cardiovascular events (nonfatal myocardial infarction, nonfatal stroke, hospitalized or treated heart failure, and cardiovascular death) and renal events (≥20% decline in the estimated glomerular filtration rate, end-stage kidney disease, and renal death). RESULTS: Overall, 652 cardiovascular events and 1268 renal events occurred during 43 970 person-years of follow-up. We observed a positive and linear relationship between systolic BP and risks of cardiovascular and renal events down to 90 mm Hg, as well as between diastolic BP and risks of renal events down to 50 mm Hg. A J-shaped trend was noted between diastolic BP and risks of cardiovascular events, but a linear relationship was revealed in participants <60 years (P for interaction <0.001). A significant increase in the risk of cardiovascular and renal outcomes was observed at systolic BP ≥130 mm Hg (versus 90-119 mm Hg) and at diastolic BP ≥90 mm Hg (versus 50-69 mm Hg). CONCLUSIONS: In people with chronic kidney disease, a higher systolic BP/diastolic BP level (≥130/90 mm Hg) is significantly associated with a greater risk of cardiovascular and renal events, indicating potential thresholds to initiate BP-lowering treatment.

4.
J Diabetes ; 2023 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-36650122

RESUMO

BACKGROUND: Studies indicate lower, comparable, and higher cardiovascular risks in women vs men in normal glucose regulation (NGR), prediabetes, and diabetes, respectively. However, this sex difference is uncertain and aging might play a part. We aimed to estimate sex differences in arterial stiffness in NGR, prediabetes, or diabetes and the potential modifications by age. METHODS: We used baseline data of 9618 participants aged ≥40 years in a large community-based cohort study in Shanghai. Glycemic status was determined by history of diabetes, fasting and 2-h post-load glucose levels, and hemoglobin A1c levels. Arterial stiffness was examined by brachial-ankle pulse wave velocity (ba-PWV). Multivariable linear regression analysis was conducted to examine the associations between sex and ba-PWV levels in glycemic and age categories. RESULTS: Before adjustment for age, women had lower, comparable, and higher ba-PWV vs men in the NGR, prediabetes, and diabetes groups, respectively. In participants aged 40-59 years, women were associated with lower ba-PWV levels in generally all glycemic strata after adjustment for age and other confounders. In participants aged ≥60 years, women were associated with significantly higher ba-PWV levels (ß coefficient = 71.5; 95% confidence interval = 23.4, 119.7) and the sex difference was attenuated in the groups of prediabetes and diabetes with a borderline significant interaction between sex and glycemic status (p for interaction = .068). CONCLUSIONS: The sex difference in cardiovascular risks in adults with NGR, prediabetes, or diabetes was dependent on age. Our findings provide new evidence for prioritizing preventive treatment against atherosclerosis in men vs women with different glycemic status.

5.
Hypertension ; 80(1): 192-203, 2023 01.
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.


Assuntos
Estudo de Associação Genômica Ampla , Hipertensão , Humanos , Hipertensão/epidemiologia , Hipertensão/genética
6.
Front Public Health ; 10: 1053269, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36579056

RESUMO

Background: Artificial intelligence technology has become a mainstream trend in the development of medical informatization. Because of the complex structure and a large amount of medical data generated in the current medical informatization process, big data technology to assist doctors in scientific research and analysis and obtain high-value information has become indispensable for medical and scientific research. Methods: This study aims to discuss the architecture of diabetes intelligent digital platform by analyzing existing data mining methods and platform building experience in the medical field, using a large data platform building technology utilizing the Hadoop system, model prediction, and data processing analysis methods based on the principles of statistics and machine learning. We propose three major building mechanisms, namely the medical data integration and governance mechanism (DCM), data sharing and privacy protection mechanism (DPM), and medical application and medical research mechanism (MCM), to break down the barriers between traditional medical research and digital medical research. Additionally, we built an efficient and convenient intelligent diabetes model prediction and data analysis platform for clinical research. Results: Research results from this platform are currently applied to medical research at Shanghai T Hospital. In terms of performance, the platform runs smoothly and is capable of handling massive amounts of medical data in real-time. In terms of functions, data acquisition, cleaning, and mining are all integrated into the system. Through a simple and intuitive interface operation, medical and scientific research data can be processed and analyzed conveniently and quickly. Conclusions: The platform can serve as an auxiliary tool for medical personnel and promote the development of medical informatization and scientific research. Also, the platform may provide the opportunity to deliver evidence-based digital therapeutics and support digital healthcare services for future medicine.


Assuntos
Inteligência Artificial , Diabetes Mellitus , Humanos , Big Data , China , Tecnologia
7.
Artigo em Inglês | MEDLINE | ID: mdl-36510667

RESUMO

BACKGROUND: Observational studies indicated obesity and glutamatergic dysfunction as potential risk factors of depression, and reported disturbance of glutamine metabolism in obese state. However, it remains unclear whether the inter-relationships between obesity, glutamine and depression are causal. METHODS: We conducted two-sample bidirectional Mendelian Randomization (MR) analyses to explore the causalities between circulating glutamine levels, specific depressive symptoms, major depressive disorder (MDD) and body mass index (BMI). Univariable MR, multivariable MR (MVMR) and linkage disequilibrium score regression (LDSR) analyses were performed. RESULTS: Genetic downregulation of glutamine was causally associated with MDD, anhedonia, tiredness, and depressed mood at the false discovery rate (FDR)-controlled significance level (estimate, -0·036∼ -0·013, P = 0·005 to P = 0·050). Elevated BMI was causally linked to lower glutamine level (estimate = -0·103, P = 0·037), as well as more severe depressed mood, tiredness, and anhedonia (estimate, 0·017∼0·050, P < 0·001 to P = 0·040). In MVMR analysis, BMI was causally related to depressed mood dependently of glutamine levels. Reversely, it showed limited evidence supporting causal effects of depression on glutamine levels or BMI, except a causal association of tiredness with elevated BMI (estimate = 0·309, P = 0·003). LDSR estimates were directionally consistent with MR results. CONCLUSION: The present study reported that higher BMI was causally associated with lower glutamine levels. Both obesity and down-regulation of glutamine were causally linked to depression.

8.
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.

9.
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
10.
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.

11.
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
12.
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.

13.
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
14.
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
15.
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 , Humanos , Hipoglicemiantes , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Estado Pré-Diabético/epidemiologia , Estudos Prospectivos , Fatores de Risco
16.
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
17.
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
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
19.
Liver Int ; 42(12): 2683-2695, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36166316

RESUMO

BACKGROUND: Lack of physical activity and excessive sitting time contributed to ectopic fat accumulation, especially in the liver. Previous studies have illustrated the harm of sedentary behaviour and the benefits of physical activity on fatty liver disease. We aimed to explore the association between the behaviour patterns and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) using isotemporal substitution model to examine the effect of replacing one behaviour to another while keeping the total time and other behaviours fixed among Chinese middle-aged and elderly population. METHODS: This study included 161 147 participants aged ≥40 years old from the nationwide, population-based cohort of the REACTION study. The International Physical Activity Questionnaire was used to measure self-reported time for sleeping, sitting, walking and moderate-to-vigorous physical activity (MVPA). MAFLD was defined by evidence of fatty liver index (FLI) ≥ 60 in addition to one of the following three patterns, namely overweight/obesity, presence of diabetes, or evidence of metabolic dysregulation. Isotemporal substitution models using logistic regression models to evaluate the association of replacement of different behaviour patterns with each other and the risk of MAFLD. RESULTS: Substitution of 60 minutes per day of sleeping, walking or total MVPA for sitting was associated with a 2%-8% reduction of MAFLD risk in overall participants. In employed individuals, replacing sitting time with occupational MVPA or nonoccupational MVPA both could bring benefits to liver steatosis. Stratified analysis found that replacing 60 minutes of sitting time with an equivalent time of other behaviour pattern could reduce approximately 8% of the risk among MAFLD participants with metabolic abnormalities. Such a relationship might be explained by the important mediated role of metabolic elements, such as waist circumference, body mass index, triglycerides and homoeostasis model assessment of insulin resistance. Furthermore, replacing sitting with MVPA showed a stronger association among participants who got enough sleep (sleep duration ≥7 hours per day). CONCLUSION: Replacing sitting with other behaviour patterns could reduce the prevalence of MAFLD, and such substitution effect was much remarkably in individuals with abnormal metabolic status. Observably, obese individuals were more likely to benefit from appropriate changes in behaviour patterns. Moreover, the analysis of sleep duration stratification appealed that the adequacy of individual sleep duration also had a significant impact on the substitution effect. It is worth noting that adjusting the time allocation of behaviour patterns might have a beneficial impact on liver-metabolic health, and these findings might help us better recognize the importance of reasonable arrangement of behaviour patterns according to the individual's situation.


Assuntos
Hepatopatias , Comportamento Sedentário , Pessoa de Meia-Idade , Adulto , Humanos , Idoso , Exercício Físico/fisiologia , Índice de Massa Corporal , Obesidade/epidemiologia , China/epidemiologia
20.
Nutr Metab Cardiovasc Dis ; 32(9): 2177-2186, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35918265

RESUMO

BACKGROUND AND AIMS: The joint effect of famine exposure and adulthood obesity on risk of dyslipidemia remains unclear. Thus, we aim to explore the joint effect of famine exposure and adulthood obesity on the risk of dyslipidemia, and the potential effect of adult general or abdominal obesity on the association between famine exposure and dyslipidemia. METHODS AND RESULTS: We conducted a community-based cohort study in 8880 subjects aged 40 years or older. Participants were divided into nonexposed, fetal-exposed, childhood-exposed, adolescent-exposed according to birth date. General obesity and abdominal obesity were defined according to body mass index (BMI: overweight≥24.0 kg/m2, obesity≥28.0 kg/m2) and waist-to-hip ratio (WHR, men/women: moderate≥0.90/0.85, high≥0.95/0.90). Dyslipidemia was defined using the National Cholesterol Education Program Adult Treatment Panel III criteria. Compared with nonexposed participants, fetal-exposed individuals had significantly increased risk of dyslipidemia (OR:1.24, 95%CI: 1.03-1.50) in the whole study. Significant increased risk of dyslipidemia related to famine exposure was observed in women [ORs (95%CIs) were 1.36 (1.05-1.76) and 1.70 (1.22-2.37) for the fetal and childhood-exposed group, respectively] but not in men. Moreover, both general and central obesity had significant multiplicative interactions with famine exposure for the risk of dyslipidemia (P for interaction = 0.0001 and < 0.0001, respectively). Significant additive interaction was found between famine exposure and WHR on risk of dyslipidemia in women, with the relative excess risk due to interaction (RERI) and 95% CI of 0.43 (0.10-0.76). CONCLUSION: Coexistence of early-life undernutrition and adulthood obesity was associated with a higher risk of dyslipidemia in later life.


Assuntos
Dislipidemias , Efeitos Tardios da Exposição Pré-Natal , Inanição , Adolescente , Adulto , Criança , China , Estudos de Coortes , Fome Epidêmica , Feminino , Humanos , Masculino , Obesidade , Obesidade Abdominal , Fatores de Risco
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