COVID-19 Rebound After VV116 vs Nirmatrelvir-Ritonavir Treatment: A Randomized Clinical Trial.

Importance: With the widespread use of anti-SARS-CoV-2 drugs, accumulating data have revealed potential viral load rebound after treatment. Objective: To compare COVID-19 rebound after a standard 5-day course of antiviral treatment with VV116 vs nirmatrelvir-ritonavir. Design, Setting, and Participants: This is a single-center, investigator-blinded, randomized clinical trial conducted in Shanghai, China. Adult patients with mild-to-moderate COVID-19 and within 5 days of SARS-CoV-2 infection were enrolled between December 20, 2022, and January 19, 2023, and randomly allocated to receive either VV116 or nirmatrelvir-ritonavir. Interventions: Participants in the VV116 treatment group received oral 600-mg VV116 tablets every 12 hours on day 1 and 300 mg every 12 hours on days 2 through 5. Participants in the nirmatrelvir-ritonavir treatment group received oral nirmatrelvir-ritonavir tablets with 300 mg of nirmatrelvir plus 100 mg of ritonavir every 12 hours for 5 days. Participants were followed up every other day until day 28 and every week until day 60. Main Outcomes and Measures: The primary outcome was viral load rebound (VLR), defined as a half-log increase in viral RNA copies per milliliter compared with treatment completion. Secondary outcomes included a reduction in the cycle threshold value of 1.5 or more, time until VLR, and symptom rebound, defined as an increase of more than 2 points in symptom score compared with treatment completion. The primary outcome and secondary outcomes were analyzed using the full analysis set. Sensitivity analyses were conducted using the per protocol set. Adverse events were analyzed using the safety analysis set. Results: The full analysis set included 345 participants (mean [SD] age, 53.2 [16.8] years; 175 [50.7%] were men) who received VV116 (n = 165) or nirmatrelvir-ritonavir (n = 180). Viral load rebound occurred in 33 patients (20.0%) in the VV116 group and 39 patients (21.7%) in the nirmatrelvir-ritonavir group (P = .70). Symptom rebound occurred in 41 of 160 patients (25.6%) in the VV116 group and 40 of 163 patients (24.5%) in the nirmatrelvir-ritonavir group (P = .82). Viral whole-genome sequencing of 24 rebound cases revealed the same lineage at baseline and at viral load rebound in each case. Conclusions and Relevance: In this randomized clinical trial of patients with mild-to-moderate COVID-19, viral load rebound and symptom rebound were both common after a standard 5-day course of treatment with either VV116 or nirmatrelvir-ritonavir. Prolongation of treatment duration might be investigated to reduce COVID-19 rebound. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2200066811.

Body size, insulin sensitivity, metabolic health and risk of cardiovascular disease in Chinese adults: Insights from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

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.

The Association between Educational Attainment and the Risk of Nonalcoholic Fatty Liver Disease among Chinese Adults: Findings from the REACTION Study.

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.

Early-life famine exposure, adulthood obesity patterns, and risk of low-energy fracture.

Malnutrition in early life increases the risk of osteoporosis, but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown. This study included 5323 community-dwelling subjects aged ⩾40 years from China. Early-life famine exposure was identified based on the participants' birth dates. General obesity was assessed using the body mass index (BMI), and abdominal obesity was evaluated with the waist-to-hip ratio (WHR). Low-energy fracture was defined as fracture occurring after the age of ⩾40 typically caused by falls from standing height or lower. Compared to the nonexposed group, the group with fetal, childhood, and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios (ORs) and 95% confidence intervals (CIs) of 3.55 (1.57-8.05), 3.90 (1.57-9.71), and 3.53 (1.05-11.88), respectively, but not in men. Significant interactions were observed between fetal famine exposure and general obesity with fracture among women (P for interaction = 0.0008). Furthermore, compared with the groups with normal BMI and WHR, the group of women who underwent fetal famine exposure and had both general and abdominal obesity had the highest risk of fracture (OR, 95% CI: 3.32, 1.17-9.40). These results indicate that early-life famine exposure interacts with adulthood general obesity and significantly increases the risk of low-energy fracture later in life in women.

Evaluating the distinct pleiotropic effects of omega-3 fatty acids on type 2 diabetes mellitus: a mendelian randomization study.

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 (ß = - 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 (ß = - 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.

Association of serum secreted protein acidic and rich in cysteine-like protein 1 with metabolic measures and dyslipidemia among Chinese adults.

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.

Obesity mediates the opposite association of education and diabetes in Chinese men and women: Results from the REACTION study.

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.

Association between triglyceride glucose index and carotid intima-media thickness in obese and nonobese adults.

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.

Association between early life famine exposure and risk of metabolic syndrome in later life.

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.

The association between early-life famine exposure and adulthood obesity on the risk of dyslipidemia.

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.

Discordance of Apolipoprotein B, Non-HDL-Cholesterol, and LDL-Cholesterol Predicts Risk of Increased Arterial Stiffness and Elevated Carotid Intima-Media Thickness in Middle-Aged and Elderly Chinese Adults.

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.

New definition of metabolic dysfunction-associated fatty liver disease with elevated brachial-ankle pulse wave velocity and albuminuria: a prospective cohort study.

A new definition of metabolic dysfunction-associated fatty liver disease (MAFLD) has recently been proposed. We aim to examine the associations of MAFLD, particularly its discordance from non-alcoholic fatty liver disease (NAFLD), with the progression of elevated brachial-ankle pulse wave velocity (baPWV) and albuminuria in a community-based study sample in Shanghai, China. After 4.3 years of follow-up, 778 participants developed elevated baPWV and 499 developed albuminuria. In comparison with the non-MAFLD group, the multivariable adjusted odds ratio (OR) of MAFLD group for new-onset elevated baPWV was 1.25 (95% confidence interval (CI) 1.01-1.55) and 1.35 (95% CI 1.07-1.70) for albuminuria. Participants without NAFLD but diagnosed according to MAFLD definition were associated with higher risk of incident albuminuria (OR 1.77; 95% CI 1.07-2.94). Patients with MAFLD with high value of hepamet fibrosis score or poor-controlled diabetes had higher risk of elevated baPWV or albuminuria. In conclusion, MAFLD was associated with new-onset elevated baPWV and albuminuria independently of body mass index, waist circumference, and hip circumference. Individuals without NAFLD but diagnosed as MAFLD had high risk of albuminuria, supporting that MAFLD criteria would be practical for the evaluation of long-term risk of subclinical atherosclerosis among fatty liver patients.

Association Between Age at Diagnosis of Type 2 Diabetes and Cardiovascular Diseases: A Nationwide, Population-Based, Cohort Study.

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.

Gestational hyperglycemia and the risk of cardiovascular diseases among elderly Chinese women: Findings from the REACTION study.

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

Association of early adulthood weight and subsequent weight change with cardiovascular diseases: Findings from REACTION study.

BACKGROUND: Excessive adiposity in adulthood is positively associated with the risk of cardiovascular disease (CVD). However, it is less studied how the risk is separately explained by early adulthood weight and later weight change, especially in Asian ancestries. METHODS: This study included 121160 participants in a large population-based cohort in China. Body weight at 20 and 40 years of age wase self-reported. Information on CVD history was obtained through standard questionnaires. RESULTS: The odds ratios (ORs) were 1.20 (95% CI, 1.10-1.31) for coronary heart disease (CHD), 1.74 (95% CI, 1.36-2.22) for myocardial infarction (MI), 1.14 (95% CI, 0.99-1.32) for stroke and 1.21 (95% CI, 1.12-1.31) for total CVD among individuals with early overweight, and became more prominent for early obesity. Meanwhile, A moderate weight gain of 2.5 kg between early adulthood and midlife significantly increased the risk of CHD (OR: 1.18, 95% CI: 1.05-1.32), stroke (OR: 1.19, 95% CI: 1.03-1.38) and total CVD (OR: 1.15, 95% CI: 1.04-1.27), and the risk escalated with higher amounts of weight gain. Conversely, a weight loss of 2.5 kg conferred lower risk of CVD compared with a stable weight. In further cross-analysis, participants with early adulthood overweight or obesity and significant weight gain afterwards exhibited the greatest risk of CVD. CONCLUSIONS: High early adulthood BMI and subsequent weight gain had both independent and combined effect on the risk of CVD after midlife. Therefore, weight management should start before early adulthood, and emphasized throughout adulthood for CVD prevention.

Associations between parity, pregnancy loss, and breastfeeding duration and risk of maternal type 2 diabetes: An observational cohort study.

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.

Age at menarche, ideal cardiovascular health metrics, and risk of diabetes in adulthood: Findings from the REACTION study.

BACKGROUND: Age at menarche was reported to be associated with the risk of diabetes. However, the impact of ideal cardiovascular health metrics (ICVHMs) on the association between age at menarche and adulthood diabetes risk was unclear. METHODS: We included 121 431 women from the nationwide, population-based cohort of the REACTION study (Risk Evaluation of Cancers in Chinese Diabetic Individuals: a Longitudinal Study). The diagnosis of diabetes was based on the oral glucose tolerance test (OGTT) and glycosylated hemoglobin (HbA1c) measurement. Logistic regression and multiplicative interaction analysis were conducted to investigate the potential interaction effect between age at menarche and ICVHMs on the development of diabetes. RESULTS: The multivariable-adjusted odds ratios of diabetes across categories of age at menarche (<14, 14-17, and > 17 years) were 1.22 (95% confidence interval [CI]: 1.17, 1.28), 1.00 (reference), and 0.89 (95% CI: 0.85, 0.93), respectively. In subgroup analysis, significant interactions were detected between total cholesterol/blood pressure levels and age at menarche regarding the risk of diabetes (P for interaction = .0091 and .0019, respectively). The increased risk associated with age at menarche <14 years was observed in participants with three or fewer ICVHMs, but not in women with four or more ICVHMs (P for interaction = .0001). CONCLUSIONS: Age at menarche was inversely associated with the risk of diabetes in adulthood in Chinese women, and it appeared to be modified by the presence of ICVHMs. Further studies are needed to clarify the precise interrelationship and the generalizability of our results.

Early-Life Famine Exposure and Risk of Cardiovascular Diseases in Later Life: Findings From the REACTION Study.

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.

Detection of diabetes and prediabetes using glycosylated hemoglobin in Chinese adults living in Shanghai: A prospective analysis.

BACKGROUND: This study aimed to evaluate the discriminative abilities of glycosylated hemoglobin (HbA1c) and to examine the optimal HbA1c cutoff values for diabetes and prediabetes in Chinese adults. METHODS: Data of a population-based cohort of Chinese adults aged ≥40 years living in Jiading District in Shanghai were used. At baseline, 9389 and 7241 participants were included to identify the optimal HbA1c cutoff values for diabetes and prediabetes, respectively using the 1999 World Health Organization criteria as reference. In addition, the follow-up data on incident diabetes of 4538 participants were used to determine the HbA1c cutoff value for prediabetes using the development of diabetes as reference. The discriminative abilities of HbA1c were evaluated using receiver operating characteristic (ROC) curves, and the optimal cutoff values were determined by Youden's index. RESULTS: The areas under the ROC curves were 0.849 for diabetes, 0.614 for prediabetes using baseline data, and 0.648 for prediabetes using follow-up data. An HbA1c cutoff value of 6.0% had the largest Youden's index to diagnose diabetes with a sensitivity of 70.2% and a specificity of 87.4%. An HbA1c cutoff value of 5.6% was indicated for prediabetes using both baseline and follow-up data. However, the sensitivity and specificity were both low (55.4% and 61.1% using an oral glucose tolerance test as reference, 64.6% and 57.1% using incident diabetes as reference). CONCLUSIONS: An HbA1c value ≥6.0% could be used to detect diabetes in Chinese adults aged ≥40 years. However, although an HbA1c value of 5.6% to 5.9% was indicated in this study, the overall discrimination of HbA1c for prediabetes was poor.

Associations of subclinical atherosclerosis with nonalcoholic fatty liver disease and fibrosis assessed by non-invasive score.

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.