The association between triglyceride-glucose index and its combination with obesity indicators and cardiovascular disease: NHANES 2003-2018.

BACKGROUND: In the American population, the relationship between the triglyceride-glucose (TyG) index and TYG combined with indicators of obesity and cardiovascular disease (CVD) and its mortality has been less well studied. METHODS: This cross-sectional study included 11,937 adults from the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Cox proportional hazards model, binary logistic regression analyses, restricted cubic spline (RCS), and receiver operating characteristic (ROC) were used to analyze the relationship between TyG and its combined obesity-related indicators and CVD and its mortality. Mediation analysis explored the mediating role of glycated hemoglobin and insulin in the above relationships. RESULTS: In this study, except for no significant association between TyG and CVD mortality, TyG, TyG-WC, TyG-WHtR, and TyG-BMI were significantly and positively associated with CVD and CVD mortality. TyG-WHtR is the strongest predictor of CVD mortality (HR 1.66, 95% CI 1.21-2.29). The TyG index correlated better with the risk of coronary heart disease (OR 2.52, 95% CI 1.66-3.83). TyG-WC correlated best with total CVD (OR 2.37, 95% CI 1.77-3.17), congestive heart failure (OR 2.14, 95% CI 1.31-3.51), and angina pectoris (OR 2.38, 95% CI 1.43-3.97). TyG-WHtR correlated best with myocardial infarction (OR 2.24, 95% CI 1.45-3.44). RCS analyses showed that most of the above relationships were linear (P-overall < 0.0001, P-nonlinear > 0.05). Otherwise, ROC curves showed that TyG-WHtR and TyG-WC had more robust diagnostic efficacy than TyG. In mediation analyses, glycated hemoglobin mediated in all the above relationships and insulin-mediated in partial relationships. CONCLUSIONS: TyG-WC and TyG-WtHR enhance CVD mortality prediction, diagnostic efficacy of CVD and its mortality, and correlation with some CVD over and above the current hottest TyG. TyG-WC and TyG-WtHR are expected to become more effective metrics for identifying populations at early risk of cardiovascular disease and improve risk stratification.

Vitamin K2 supplementation improves impaired glycemic homeostasis and insulin sensitivity for type 2 diabetes through gut microbiome and fecal metabolites.

BACKGROUND: There is insufficient evidence for the ability of vitamin K2 to improve type 2 diabetes mellitus symptoms by regulating gut microbial composition. Herein, we aimed to demonstrate the key role of the gut microbiota in the improvement of impaired glycemic homeostasis and insulin sensitivity by vitamin K2 intervention. METHODS: We first performed a 6-month RCT on 60 T2DM participants with or without MK-7 (a natural form of vitamin K2) intervention. In addition, we conducted a transplantation of the MK-7-regulated microbiota in diet-induced obesity mice for 4 weeks. 16S rRNA sequencing, fecal metabolomics, and transcriptomics in both study phases were used to clarify the potential mechanism. RESULTS: After MK-7 intervention, we observed notable 13.4%, 28.3%, and 7.4% reductions in fasting serum glucose (P = 0.048), insulin (P = 0.005), and HbA1c levels (P = 0.019) in type 2 diabetes participants and significant glucose tolerance improvement in diet-induced obesity mice (P = 0.005). Moreover, increased concentrations of secondary bile acids (lithocholic and taurodeoxycholic acid) and short-chain fatty acids (acetic acid, butyric acid, and valeric acid) were found in human and mouse feces accompanied by an increased abundance of the genera that are responsible for the biosynthesis of these metabolites. Finally, we found that 4 weeks of fecal microbiota transplantation significantly improved glucose tolerance in diet-induced obesity mice by activating colon bile acid receptors, improving host immune-inflammatory responses, and increasing circulating GLP-1 concentrations. CONCLUSIONS: Our gut-derived findings provide evidence for a regulatory role of vitamin K2 on glycemic homeostasis, which may further facilitate the clinical implementation of vitamin K2 intervention for diabetes management. TRIAL REGISTRATION: The study was registered at https://www.chictr.org.cn (ChiCTR1800019663).

Association of circulation very long chain saturated fatty acids with depression in NHANES 2011-2014.

BACKGROUND: Recent studies have shown that elevated levels of medium and long chain saturated fatty acids are associated with an increased risk of depression. However, little is known about the effect of very long chain saturated fatty acids (VLSFAs) on depression. Therefore, our study aimed to examine the association between VLSFAs and depression in the US adult population. METHODS: A total of 2706 participants with serum VLSFAs detection from NHANES 2011-2014 were included in the study. Logistic regression models were used to evaluate the association between quartile levels of serum VLSFAs (20:0, 22:0, 23:0, 24:0, and total VLSFA) and depression. RESULTS: After adjusting for multiple variables, we found that increased circulating levels of 22:0, 23:0, 24:0 and total VLSFA were linearly associated with a reduced risk of depression (model 3, Q4 OR: 0.658, 95 % CI: 0.438-0.989, P-trend = 0.023; OR: 0.515, 95 % CI: 0.339-0.782, P-trend<0.001; OR: 0.556, 95 % CI: 0.370-0.835, P-trend = 0.003; OR: 0.652, 95 % CI: 0.435-0.976, P-trend = 0.021, respectively). Additionally, individuals with the highest serum ratios of 22:0/16:0, 23:0/16:0, 24:0/16:0 and total VLSFA/16:0 also had a lower risk of depression after adjusting for multiple variables compared to the group with the lowest serum VLSFAs/16:0 (P-trend = 0.001, <0.001, 0.001 and 0.004, respectively). Moreover, the decreasing trend of depression associated with increased VLSFAs/18:0 remained significant. CONCLUSION: In conclusion, our findings suggest that increased circulating levels of 22:0, 23:0, 24:0 and total VLSFA may have a protective effect against the risk of depression.

Association of Circulating Very Long-Chain Saturated Fatty Acids With Cardiovascular Mortality in NHANES 2003-2004, 2011-2012.

CONTEXT: Limited studies have shown a protective effect of very long-chain saturated fatty acids (VLSFAs) on healthy aging, diabetes, heart failure, and risk factors related to cardiovascular disease (CVD), but the role of VLSFAs on mortality risk is unclear. OBJECTIVE: We aimed to investigate the association of serum docosanoic acid (C22:0) and serum lignoceric acid (C24:0) with all-cause and disease-specific mortality and to confirm the effect of VLSFAs on mortality risk in the whole, hyperlipidemia, and hypertensive populations. METHODS: A total of 4132 individuals from the 2003-2004, 2011-2012 National Health and Nutrition Examination Survey (NHANES) were included in this study. There were 1326 and 1456 participants in the hyperlipidemia and hypertensive population, respectively. Mortality information was confirmed using the National Death Index (NDI). Multiple model calibration was performed using Cox regression analysis for known risk factors to explore the association between circulating VLSFAs and all-cause or CVD or coronary heart disease (CHD) mortality. RESULTS: In the whole population, individuals with higher circulating C22:0 and C24:0 as a percentage of total serum fatty acid levels reduced the risks of mortality of all-cause (C22:0: HR = .409; 95% CI, 0.271-0.618; C24:0: HR = 0.430; 95% CI, 0.283-0.651), CVD (C22:0: HR = 0.286; 95% CI, 0.134-0.612; C24:0: HR = 0.233; 95% CI, 0.101-0.538), and CHD (C22:0: HR = 0.401; 95% CI, 0.187-0.913; C24:0: HR = 0.263; 95% CI, 0.082-0.846). Similar to the whole population, individuals with higher circulating C22:0 and C24:0 as a percentage of total serum fatty acid levels in the hyperlipidemia and hypertensive populations were also protective for all-cause, CHD, and CVD mortality. CONCLUSION: Our results confirm the protective effect of high levels of circulating VLSFAs (C22:0 and C24:0) on CVD, CHD, and all causes of death in the whole, hyperlipidemia, and hypertensive populations.

Sleep patterns and risks of incident cardiovascular disease and mortality among people with type 2 diabetes: a prospective study of the UK Biobank.

BACKGROUND: To explore the relationship between sleep patterns and cardiovascular disease (CVD) incidence and mortality risk in a population with type 2 diabetes through a UK Biobank sample. METHODS: A total of 6860 patients with type 2 diabetes were included in this study. Five sleep factors (including Chronotype, sleep duration, insomnia, daytime sleepiness, and snoring) were collected as a questionnaire. The calculation generates a sleep score of 0-5, and then three sleep patterns were defined based on the sleep scores: poor sleep pattern (0-2), Intermediate sleep pattern (3-4), and healthy sleep pattern (5). HRs and 95% confidence intervals were calculated by multivariate COX proportional risk model adjustment. Restricted cubic splines were used to validate linear associations between sleep scores CVD events. RESULTS: Our results found a reduced risk of CVD events in individuals with healthy sleep patterns compared to participants with poor sleep patterns. CVD Mortality (HR, 0.690; 95% CI 0.519-0.916), ASCVD (Atherosclerosis CVD) (HR, 0.784; 95% CI 0.671-0.915), CAD (Coronary Artery Disease) (HR, 0.737; 95% CI 0.618-0.879), PAD (Peripheral Arterial Disease) (HR, 0.612; 95% CI 0.418-0.896), Heart Failure (HR, 0.653; 95% CI 0.488-0.875). Restricted cubic spline responded to a negative linear correlation between sleep scores and CVD Mortality, ASCVD, CAD, PAD, and Heart Failure. CONCLUSIONS: Healthy sleep patterns are significantly associated with a reduced risk of CVD Mortality, ASCVD, CAD, PAD, and Heart Failure in the diabetes population.

Xanthine oxidase promotes hepatic lipid accumulation through high fat absorption by the small intestine.

Background & Aims: There are no studies investigating the direct effects of elevated xanthine oxidase (XO) on lipid metabolism disorders. Here, we aimed to clarify the role of XO in lipid metabolism in a prospective cohort study and elucidate the underlying mechanisms. Methods: The association between serum XO activity and metabolic associated steatotic liver disease (MASLD) was examined in Cox proportional hazard models in a population-based cohort of 3,358 participants (20-75 years) at baseline. In addition, mouse models were used to investigate the underlying mechanism for the association between overexpression of XO and the lipid metabolism disorders. Results: After an average 5.8 years of follow up, we found elevated serum XO activity was associated with an increased risk of developing MASLD (hazard ratio [HR]: 2.08; 95% CI: 1.44-3.01; p-trend <0.001). Moreover, serum XO activity was significantly associated with serum triglyceride levels (r = 0.68, p <0.001). We demonstrated that hepatic XO expression increased in liver samples from patients with MASLD. Using tissue-specific Xdh knockin mice, we observed rapid lipid metabolism disorders under a high-fat diet rather than a normal chow diet. We found that XO overexpression promotes the absorption of excess dietary fat in the small intestine. Inhibition of XO also significantly reduced the absorption of fat in mice fed a high-fat diet. Conclusions: Our study clarified the association between serum XO activity levels and the development of MASLD in a large population-based prospective cohort study. Furthermore, our mouse models demonstrated that XO overexpression promotes lipid accumulation through mechanisms involving excessive fat absorption by the small intestine. Impact and implications: Using a prospective population-based cohort and various animal models, we have identified novel mechanisms by which xanthine oxidase regulates lipid metabolism. Our findings indicate that xanthine oxidase overexpression promotes lipid accumulation by increasing the absorption of excess dietary fat and possibly facilitating lipid transport in vivo. These results could be important for the development of therapies to treat diseases associated with lipid metabolism disorders.