We examined the causal direction between gut microbiota–dependent metabolite trimethylamine N-oxide (TMAO) or its predecessors and cardiometabolic diseases, such as risk of type 2 diabetes mellitus (T2DM), coronary artery disease (CAD), myocardial infarction (MI), stroke, atrial fibrillation (AF), and chronic kidney disease (CKD). We used genetic variants as instruments to test the causal associations. Genetically predicted higher TMAO and carnitine were not associated with higher odds of T2DM, AF, CAD, MI, stroke, and CKD after Bonferroni correction (P ≤ 0.0005). However, we observed that genetically increased choline showed a suggestive association with higher risk of T2DM (odds ratio 1.84 [95% CI 1.00–3.42] per 10 units, P = 0.05). In contrast, genetically predicted higher betaine (0.68 [0.48–0.95] per 10 units, P = 0.023) was suggestively associated with a lower risk of T2DM. We observed a suggestive association of genetically increased choline with a lower level of body fat percentage (β ± SE −0.28 ± 0.11, P = 0.013) but a higher estimated glomerular filtration rate (0.10 ± 0.05, P = 0.034). We further found that T2DM (0.130 ± 0.036, P < 0.0001) and CKD (0.483 ± 0.168, P = 0.004) were causally associated with higher TMAO levels. Our Mendelian randomization findings support that T2DM and kidney disease increase TMAO levels and that observational evidence for cardiovascular diseases may be due to confounding or reverse causality.

Background: Associations between the frequency of social and intellectual activities and cognitive trajectories are understudied in Chinese middle-aged and older adults. We aimed to examine this association in a nationally representative longitudinal study. Methods: The China Health and Retirement Longitudinal Study (CHARLS) is a nationally representative sample of Chinese middle-aged and older participants. The frequency of social and intellectual activities was measured at baseline. Interview-based cognitive assessments of orientation and attention, episodic memory, and visuospatial skills and the calculation of combined global scores were assessed every 2 years from 2011 to 2016. Cognitive aging trajectories over time were analyzed using group-based trajectory modeling, and the associations of the trajectory memberships with social and intellectual activities were analyzed using multinomial logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) were reported. Results: Among 8204 participants aged 50–75 years at baseline, trajectory analysis identified three longitudinal patterns of cognitive function based on the global cognitive scores: “persistently low trajectory” (n = 1550, 18.9%), “persistently moderate trajectory” (n = 3194, 38.9%), and “persistently high trajectory” (n = 3460, 42.2%). After adjustment for sociodemographic variables, lifestyles, geriatric symptoms, and health conditions, more frequent intellectual activities (OR 0.54, 95% CI 0.38–0.77) and social activities (OR 0.79, 95% CI 0.65–0.95) were both associated with a lower likelihood of being in the “persistently low trajectory” for global cognitive function. Conclusions: These findings suggested that more frequent social and intellectual activities were associated with more favorable cognitive aging trajectories.

Alcohol misuse is a leading cause of morbidity and mortality.¹ Alcohol consumption is associated with a uniformly increased risk of hypertension and stroke, regardless of dose,² and heavy and binge drinking is associated with a higher risk of cardiovascular disease.³ However, studies have also found that low to moderate alcohol consumption is associated with protective effects against cardiovascular diseases.^4-6 Besides its role in physical health, low to moderate alcohol consumption has been shown to play a role in the development of cognitive impairment and dementia, conditions that are highly associated with cardiovascular diseases, although the findings are mixed. Specifically, some studies have reported benefits to cognitive function associated with low to moderate alcohol consumption,^7-11 whereas others have found no, minimal, or even adverse effects associated with alcohol consumption.^12-15 The Nurses’ Health Study¹¹ followed up with approximately 11 000 participants for 2 years and found that moderate drinkers perform better on general cognitive function and verbal memory tests and have slower rates of decline with time on these 2 cognitive functions compared with nondrinkers. Similarly, a 10-year follow-up study among 7153 British civil servants¹⁶ identified a protective association between low alcohol consumption and rates of global cognitive function and executive function decline compared with never drinking among women but not among men. By contrast, the Whitehall II imaging substudy¹⁵ followed up with 550 participants for more than 30 years and found that even moderate drinking is associated with cognitive function decline.

Background Self-reported diabetes has been found to be valid to evaluate people's diabetes status in the population of several countries. However, no such study has been conducted to assess the validity of self-reported diabetes in the Chinese population, the largest population with the highest rate of diabetes. The aim of our study is to evaluate the validity of self-reported diabetes among the middle-aged and older Chinese population. Methods Data from 11 601 participants, aged ≥45, of the China Health and Retirement Longitudinal Study (CHARLS) during 2011–2012, were analysed. Prevalent self-reported diabetes was compared with reference definition defined by fasting glucose, glycated haemoglobin and medication use. Sensitivity, specificity, positive predicted value, negative predicted value and κ value were calculated overall, by 5-year age groups, by education levels and by living areas. Results The sensitivity of prevalent self-reported diabetes was 41.5%, and the specificity was 98.6%. The sensitivity of self-reported diabetes increased with education levels, and was much higher among urban residents than rural residents (58.2% vs 35.0%). The specificity was above 98% among all age groups, in different education levels, and in rural and urban areas. Self-reported diabetes had substantial agreement with reference definition among participants with above vocational school education or those living in urban areas (κ=0.658 and 0.646, respectively). Conclusions Although the sensitivity of self-reported diabetes was poor among middle-aged and older Chinese adults, the specificity and positive predictive values were fairly good. Furthermore, self-reported diabetes performed well among those with more than vocational school educations or those living in urban areas.

OBJECTIVE: To test the causal effect of childhood BMI on adult cardiometabolic diseases using a Mendelian randomization analysis. RESEARCH DESIGN AND METHODS: We used 15 single nucleotide polymorphisms as instrumental variables for childhood BMI to test the causal effect of childhood BMI on cardiometabolic diseases using summary-level data from consortia. RESULTS: We found that a 1-SD increase in childhood BMI (kg/m2) was associated with an 83% increase in risk of type 2 diabetes (odds ratio [OR] 1.83 [95% CI 1.46, 2.30]; P = 2.5 × 10−7) and a 28% increase in risk of coronary artery disease (CAD) (OR 1.28 [95% CI 1.17, 1.39]; P = 2.1 × 10−8) at the Bonferroni-adjusted level of significance (P < 0.017) in adults. In addition, a 1-SD increase in childhood BMI was associated with a 0.587-SD increase in adulthood BMI (kg/m2), a 0.062-SD increase in hip circumference (cm), a 0.602-SD increase in waist circumference (cm), a 0.111 pmol/L increase in log fasting insulin, a 0.068 increase in log-transformed HOMA of ß-cell function (%), a 0.126 increase in log-transformed HOMA of insulin resistance (%), and a 0.109-SD increase in triglyceride (mg/dL) but a 0.138-SD decrease in HDL (mg/dL) in adults at the Bonferroni-adjusted level of significance (P < 0.0026). CONCLUSIONS: A genetic predisposition to higher childhood BMI was associated with increased risk of type 2 diabetes and CAD in adult life. These results provide evidence supportive of a causal association between childhood BMI and these outcomes.

Background: The Chinese Great Famine caused widespread starvation in 1959–1961. Its long-term association with depressive symptoms has not been studied.Aims: To estimate the burden of depressive symptoms and the association of famine exposure with depressive symptoms.Method: The China Health and Retirement Longitudinal Study is a nationwide representative survey of 17 708 Chinese adults aged ≥45. Propensity score matching and modified Poisson regression were used to evaluate the association between self-reported famine exposure in early life and depressive symptoms among the overall participants. Such associations were also assessed by developmental stage using modified Poisson regression and logistic regression.Results: The prevalence of depressive symptoms was 26.2% (95% CI 25.1–27.3%) in 2011. As defined by loss of family members because of starvation, 11.6% (95% CI 10.1–13.1%) of this population experienced severe famine. When compared with participants who did not experience starvation, those who had experienced severe famine during fetal, mid-childhood, young-teenage and early-adulthood stages had 1.87 (95% CI 1.36–2.55), 1.54 (95% CI 1.23–1.94), 1.47 (95% CI 1.09–2.00) and 1.77 (95% CI 1.42–2.21) times higher odds of having depressive symptoms in late adulthood, respectively. The first two trimesters of pregnancy were a critical time window during the fetal stage when severe famine had a stronger association with depressive symptoms. Famine during infant, toddler, preschool or teenage stages was not associated with depressive symptoms. Overall, famine contributed to 13.6% of the depressive symptom burden in this population.Conclusions: The Chinese Great Famine contributed substantially to the burden of depressive symptoms in China.Declaration of interest: None.