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Aims: To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. Materials and Methods: We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. Results: During a mean 3.61‐year follow‐up period, obese individuals with insulin sensitivity (multivariable‐adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37–2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13–1.89) still exhibited increased CVD risks, when compared to their normal‐weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal‐weight individuals (HR 0.91, 95% CI 0.53–1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. Conclusions: This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity. [ABSTRACT FROM AUTHOR]

Background: Observational studies and conventional Mendelian randomization (MR) studies showed inconclusive evidence to support the association between omega-3 fatty acids and type 2 diabetes. We aim to evaluate the causal effect of omega-3 fatty acids on type 2 diabetes mellitus (T2DM), and the distinct intermediate phenotypes linking the two. Methods: Two-sample MR was performed using genetic instruments derived from a recent genome-wide association study (GWAS) of omega-3 fatty acids (N = 114,999) from UK Biobank and outcome data obtained from a large-scale T2DM GWAS (62,892 cases and 596,424 controls) in European ancestry. MR-Clust was applied to determine clustered genetic instruments of omega-3 fatty acids that influences T2DM. Two-step MR analysis was used to identify potential intermediate phenotypes (e.g. glycemic traits) that linking omega-3 fatty acids with T2DM. Results: Univariate MR showed heterogenous effect of omega-3 fatty acids on T2DM. At least two pleiotropic effects between omega-3 fatty acids and T2DM were identified using MR-Clust. For cluster 1 with seven instruments, increasing omega-3 fatty acids reduced T2DM risk (OR: 0.52, 95%CI 0.45–0.59), and decreased HOMA-IR (β = − 0.13, SE = 0.05, P = 0.02). On the contrary, MR analysis using 10 instruments in cluster 2 showed that increasing omega-3 fatty acids increased T2DM risk (OR:1.10; 95%CI 1.06–1.15), and decreased HOMA-B (β = − 0.04, SE = 0.01, P = 4.52 × 10–5). Two-step MR indicated that increasing omega-3 fatty acid levels decreased T2DM risk via decreasing HOMA-IR in cluster 1, while increased T2DM risk via decreasing HOMA-B in cluster 2. Conclusions: This study provides evidence to support two distinct pleiotropic effects of omega-3 fatty acids on T2DM risk influenced by different gene clusters, which could be partially explained by distinct effects of omega-3 fatty acids on insulin resistance and beta cell dysfunction. The pleiotropic feature of omega-3 fatty acids variants and its complex relationships with T2DM need to be carefully considered in future genetic and clinical studies. [ABSTRACT FROM AUTHOR]

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 (β[SE] 0.0387 [0.0037]) and negative in women (β[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. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

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. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Objectives: Nationwide studies focusing on the impact of early-onset type 2 diabetes and obesity on the development of cardiovascular diseases (CVD) are limited in China. We aimed to investigate the association between age at diagnosis of type 2 diabetes and the risk of CVD, and to further examine the modifying effect of obesity on this association among Chinese adults. Methods: This study included 23,961 participants with previously diagnosed diabetes from a large nationwide population-based cohort study across mainland China. With an interviewer-assisted questionnaire, we collected detailed information on CVDs. Logistic regression analysis was used to evaluate the risk of CVDs associated with age at diagnosis of diabetes. Results: Compared with patients with late-onset diabetes (≥60 years), those with earlier-onset diabetes had increased risks for CVD, with adjusted ORs (95% CIs) of 1.72 (1.36-2.17), 1.52 (1.31-1.75) and 1.33 (1.19-1.48) for patients diagnosed aged <40, 40-49 and 50-59 years, respectively. Each 5-year earlier age at diagnosis of type 2 diabetes was significantly associated with 14% increased risk of CVD (OR, 1.14; 95%CI, 1.11-1.18). This association was more prominent for patients with obesity than those with normal body mass index (BMI). Significant interaction was detected between age at diagnosis and BMI categories on CVD risk (P for interaction=0.0457). Conclusion: Early-onset type 2 diabetes was significantly associated with higher risk of CVD, and this association was more prominent among patients with obesity. [ABSTRACT FROM AUTHOR]

This article, titled "Front Cover," is based on a study conducted in China called the China Cardiometabolic Disease and Cancer Cohort (4C) study. The study examines the relationship between body size, insulin sensitivity, metabolic health, and the risk of cardiovascular disease in Chinese adults. The study involved a large number of participants and provides insights into these important health factors. The article is authored by a diverse group of researchers and provides valuable information for individuals conducting research on these topics. [Extracted from the article]

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Diabetes is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background & Aims: Nonalcoholic fatty liver disease (NAFLD) has been considered as a risk factor of adverse cardiovascular prognosis, but the relationship between subclinical atherosclerosis and NAFLD remains controversial. We aimed to investigate the impact of subclinical atherosclerosis on incident NAFLD and liver fibrosis. Methods: We included 3433 subjects aged ≥40 years and free of NAFLD. Brachial‐ankle pulse wave velocity (ba‐PWV) and carotid intima‐media thickness (CIMT) were measured at baseline to assess subclinical atherosclerosis status. At follow‐up visit, NAFLD was diagnosed by hepatic ultrasound and fibrosis was assessed by NAFLD fibrosis score (NFS), fibrosis‐4 score (FIB‐4) and aspartate aminotransferase to platelet ratio index (APRI). Results: A total of 654 (19.1%) subjects developed NAFLD during the follow‐up period of 4.3 years. In the multivariate logistic regression models, each standard deviation (SD) increment of ba‐PWV was associated with 20% (95% confidence interval [CI] 1.07‐1.33), 22% (95% CI 1.08‐1.39), 17% (95% CI 1.04‐1.32) and 37% (95% CI 1.07‐1.75) higher risk of incident NAFLD, higher NFS, FIB‐4 and APRI respectively. Compared with the lowest quartile of ba‐PWV, the highest quartile ba‐PWV had 63% (95% CI 1.20‐2.22), 112% (95% CI 1.42‐3.17), 86% (95% CI 1.28‐2.69) and 201% (95% CI 1.29‐7.04) higher risk of incident NAFLD, higher NFS, FIB‐4 and APRI respectively. Besides, per SD increase of CIMT was associated with a 12% (95% CI 1.01‐1.24) higher risk of incident NAFLD. Conclusions: Increased ba‐PWV was independently associated with incident NAFLD and higher probability of fibrosis, whereas CIMT was associated with incident NAFLD but not with fibrosis. [ABSTRACT FROM AUTHOR]

Background/aims: : Low educational attainment is a well-established risk factor for nonalcoholic fatty liver disease (NAFLD) in developed areas. However, the association between educational attainment and the risk of NAFLD is less clear in China., Methods: : A cross-sectional study including over 200,000 Chinese adults across mainland China was conducted. Information on education level and lifestyle factors were obtained through standard questionnaires, while NAFLD and advanced fibrosis were diagnosed using validated formulas. Outcomes included the risk of NAFLD in the general population and high probability of fibrosis among patients with NAFLD. Logistic regression analysis was employed to estimate the risk of NAFLD and fibrosis across education levels. A causal mediation model was used to explore the potential mediators., Results: : Comparing with those receiving primary school education, the multi-adjusted odds ratios (95% confidence intervals) for NAFLD were 1.28 (1.16 to 1.41) for men and 0.94 (0.89 to 0.99) for women with college education after accounting for body mass index. When considering waist circumference, the odds ratios (95% CIs) were 0.94 (0.86 to 1.04) for men and 0.88 (0.80 to 0.97) for women, respectively. The proportions mediated by general and central obesity were 51.00% and 68.04% for men, while for women the proportions were 48.58% and 32.58%, respectively. Furthermore, NAFLD patients with lower educational attainment showed an incremental increased risk of advanced fibrosis in both genders., Conclusions: : In China, a low education level was associated with a higher risk of prevalent NAFLD in women, as well as high probability of fibrosis in both genders.

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 &lt; 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 (β= -0.06, P=0.02). The prevalence of dyslipidemia decreased across the sparcl1 quartiles (P for trend &lt;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 &gt; 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., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Hu, Wang, Lin, Qi, Lin, Jia, Zhu, Wu, Li, Wang, Zhao, Xu, Xu, Wang, Ning, Bi, Li, Chen, Dai and Lu.)

Background: Apolipoprotein B (apoB) and non-high-density lipoprotein cholesterol (non-HDL-C) have been shown to predict cardiovascular disease (CVD) even in the case of low levels of low-density lipoprotein cholesterol (LDL-C). We aimed to investigate whether the discordance between LDL-C and apoB or non-HDL-C was associated with arterial stiffness and elevated carotid intima-media thickness (CIMT) in middle-aged and elderly adults., Methods: A total of 5,279 Chinese adults free of CVD at baseline were included and followed with a mean follow-up of 4.3 years. Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) and pulse pressure (PP). The associations of apoB, non-HDL-C, and LDL-C with arterial stiffness or elevated CIMT were examined with logistic regression models using either continuous scales by restricted cubic splines or categories of concordant and discordant values defined by medians., Results: High apoB but not LDL-C was associated with elevated baPWV or PP. High apoB, non-HDL-C, and LDL-C were all associated with elevated CIMT ( p < 0.05). Individuals with low levels of LDL-C and discordantly high apoB or non-HDL-C compared to those with concordantly low apoB or non-HDL-C demonstrated higher risks of elevated baPWV [ORs (95% CI) of 1.40 (1.03-1.91) and 1.56 (1.12-2.18), respectively] and elevated PP [ORs (95% CI) of 1.61 (1.19-2.18) and 1.55 (1.12-2.15), respectively]. While, discordant high LDL-C with low apoB was associated with an increased risk of elevated CIMT (OR, 1.74; 95% CI, 1.13-2.69)., Conclusion: Discordance analysis revealed that elevated apoB or non-HDL-C was a better predictor of risk of arterial stiffness, whereas LDL-C for elevated CIMT., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jia, Qi, Zheng, Lin, Hu, Zhu, Cao, Wu, Qi, Wei, Zhang, Xu, Xu, Wang, Zhao, Chen, Li, Wang, Bi and Lu.)

Background: Parity, pregnancy loss, and breastfeeding duration were found to be associated with diabetes. However, the results are inconsistent. Also, no epidemiological studies have examined the association of these reproductive factors with diabetes in the same large population. We aim to investigate the associations between parity, pregnancy loss, breastfeeding duration, and the risk of maternal diabetes in middle-aged and elderly Chinese females., Methods: We included 131 174 females aged ≥40 years from the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study). Multivariable linear regression and logistic regression were used to assess the association between parity, pregnancy loss, and breastfeeding duration and type 2 diabetes., Results: The number of parities and breastfeeding duration were positively related to fasting plasma glucose, 2-hour postload glucose, glycosylated hemoglobin, and homeostatic model assessment of insulin resistance. Compared with those with one birth, nulliparous women or women with 2 or ≥3 births had a significantly increased risk of diabetes. The odds ratios (OR) and 95% confidence intervals (CI) were 1.27 (1.10-1.48), 1.17 (1.12-1.22), and 1.28 (1.21-1.35), respectively. Compared with women without pregnancy loss, those who underwent 2 (OR 1.09; 95% CI, 1.04-1.14) or ≥3 pregnancy losses (OR 1.11; 95% CI, 1.04-1.18) had an increased risk of diabetes. Moreover, women with a breastfeeding duration ≥0 to 6 months (OR 0.82; 95% CI, 0.75-0.90) and ≥6 to 12 months (OR 0.94; 95% CI, 0.89-0.99) had a significantly lower risk of diabetes., Conclusions: Nulliparous women or women with multiparity or more than one pregnancy loss have an increased risk of diabetes in later life, while women who breastfeed more than 0 to 12 months have a lower risk of diabetes., (© 2021 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Background Previous studies reported that early-life exposure to undernutrition is associated with the risk of diabetes mellitus and metabolic syndrome in adulthood, but the association with risk of cardiovascular disease (CVD) later in life remains unclear. The current study aimed to investigate whether exposure to Chinese famine in early life is associated with risk of CVD. Methods and Results We used data from REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal Study), which recruited a total of 259 657 community-dwelling adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. Compared with the nonexposed participants, those who had been exposed to famine in early life had a significantly increased risk of total CVD, myocardial infarction, stroke, and coronary heart disease. In the multivariable-adjusted logistic regression model, the odds ratios (95% CI) for total CVD, myocardial infarction, stroke, and coronary heart disease in fetal famine exposure were 1.35 (1.20-1.52), 1.59 (1.08-2.35), 1.40 (1.11-1.78), and 1.44 (1.26-1.65), respectively; those odds ratios in childhood famine exposure were 1.59 (1.40-1.81), 2.20 (1.52-3.20), 1.82 (1.45-2.28), and 1.80 (1.56-2.09), respectively; and those in adolescent famine exposure were 1.52 (1.27-1.81), 2.07 (1.28-3.35), 1.92 (1.42-2.58), and 1.83 (1.50-2.24), respectively. The main finding of our study is that, compared with those who lived in the less severely affected famine area, individuals in the severely affected famine area had significantly increased risk of total CVD in all 3 exposed groups. Conclusions Early-life exposure to undernutrition is associated with significantly increased risk of CVD in later life, especially among those who were in the severely affected famine area.