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.

The study aimed to evaluate the body composition of patients with mitochondrial diseases (MD) and correlate it with disease severity. Overall, 89 patients (age ≥ 18 years) with MD were recruited, includin g 49 with chronic progressive external ophthalmoplegia (CPEO) and 40 with mitochondrial encephalomyopathy with lactate acidosis and stroke-like episodes (MELAS). Body composition, including fat mass index (FMI), fat-free mass index (FFMI), skeletal muscle mass index (SMI), and appendicular skeletal muscle mass index (ASMI), were examined using multifrequency bioelectric impedance analysis. Clinical assessments, including muscle strength, usual gait speed, and disease severity determined by the Newcastle Mitochondrial Disease Adult Scale score (NMDAS), were performed. The comparisons between patients group and age- and gender-matched healthy controls, as well as the correlations between anthropometric measurements, body composition, and disease severity were analyzed. Height, weight, body mass index (BMI), FFMI, SMI, and ASMI were significantly lower in patients with MD than in healthy controls. Notably, low muscle mass was noted in 69.7% (62/89) of MD patients, with 22 patients also presenting with compromised physical performance as indicated by decreased gait speed, resulting in 24.7% satisfied the sarcopenia diagnostic criteria. Disease severity was more negatively correlated with ASMI than it was with height, weight, and BMI. Subgroup analysis showed that in the MELAS subgroup, disease severity was negatively correlated with height, weight, and ASMI; whereas in the CPEO subgroup, it was only negatively correlated with ASMI and SMI. Additionally, ASMI was positively associated with muscle strength. Altogether, compared with BMI, ASMI is a more sensitive biomarker predicting disease severity of MD, both in MELAS and CPEO patients.

BackgroundThere are various parameters to analyze obesity, however, no standard reference to predict, screen or diagnose PCOS with various obesity parameters has been established, and the accuracy of these parameters still needs to be studied.This study was to use the receiver operating characteristic (ROC) curve to explore the different values of three obesity parameters, body mass index (BMI), waist circumference (WC) and percentage of body fat (PBF) in the diagnosis of polycystic ovary syndrome (PCOS) in Chinese childbearing women.MethodsThree hundred patients who were diagnosed with PCOS at Center of Reproductive Medicine and Genetics of Peking University First Hospital were enrolled in this study, and 110 healthy age-matched women were enrolled as controls. The characteristics of BMI, WC and PBF in PCOS patients were analyzed.ResultsCompared with the control group, all the three obesity parameters were significantly increased in PCOS group. In terms of ROC area under the curve, WC > PBF > BMI, and they were all significantly different from those of the control. At a cut-off point of 80.5 cm, WC has a sensitivity of 73.6 % and a specificity of 85 % in diagnosis of PCOS; At a cut-off point of 29 %, PBF has a sensitivity of 88.2 % and a specificity of 57.7 % in diagnosis of PCOS; and at a cut-off point of 26.6 kg/m2, BMI has a sensitivity of 54.5 % and a specificity of 98 % in diagnosis of PCOS.ConclusionWC, BMI and PBF are valuable in screening and diagnosis of PCOS in Chinese childbearing women. PBF can be used to screen PCOS as it has a better sensitivity, while BMI can be used in the diagnosis of PCOS as it has a better specificity.