Temporal relationship between hepatic steatosis and fasting blood glucose elevation: a longitudinal analysis from China and UK.

BACKGROUND: The link between nonalcoholic fatty liver disease and type 2 diabetes has not been fully established. We investigated the temporal relationship between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), quantitatively assessed the impact, and evaluated the related mediation effect. METHODS: This study involved participants from the China Multi-Ethnic Cohort Study and the UK Biobank. We performed cross-lagged path analysis to compare the relative magnitude of the effects between NAFLD and T2D using two-period biochemical data. Hepatic steatosis and fasting blood glucose elevation (FBG) represented NAFLD and T2D respectively. We fitted two separate Cox proportional-hazards models to evaluate the influence of hepatic steatosis on T2D. Furthermore, we applied the difference method to assess mediation effects. RESULTS: In cross-lagged path analyses, the path coefficients from baseline hepatic steatosis to first repeat FBG (ßCMEC = 0.068, ßUK-Biobank = 0.033) were significantly greater than the path coefficients from baseline FBG to first repeat hepatic steatosis (ßCMEC = 0.027, ßUK-Biobank = -0.01). Individuals with hepatic steatosis have a risk of T2D that is roughly three times higher than those without the condition (HR = 3.478 [3.314, 3.650]). Hepatic steatosis mediated approximately 69.514% of the total effect between obesity and follow-up T2D. CONCLUSIONS: Our findings contribute to determining the sequential relationship between NAFLD and T2D in the causal pathway, highlighting that the dominant pathway in the relationship between these two early stages of diseases was the one from hepatic steatosis to fasting blood glucose elevation. Individuals having NAFLD face a significantly increased risk of T2D and require long-term monitoring of their glucose status as well.

Temporal relationship between hepatic steatosis and blood pressure elevation and the mediation effect in the development of cardiovascular disease.

The temporal relationship between non-alcoholic fatty liver disease (NAFLD) and hypertension remains highly controversial, with ongoing debates on whether NAFLD induces hypertension or vice versa. We employed cross-lagged panel models to investigate the temporal relationship between hepatic steatosis (assessed by Fatty Liver Index [FLI] in the main analysis, and by Proton Density Fat Fraction [PDFF] in the validation study) and blood pressure (systolic and diastolic blood pressure [SBP/ DBP]). Subsequently, we employed causal mediation models to explore the mediation effect in CVD development, including ischemic heart disease and stroke. The main analysis incorporated repeated measurement data of 5,047 participants from the China Multi-Ethnic Cohort (CMEC) and 5,685 participants from the UK Biobank (UKB). In both cohorts, the path coefficients from FLI to blood pressure were significant and greater than the path from blood pressure to FLI, with ßFLI→SBP = 0.081, P < 0.001 versus ßSBP→FLI = 0.020, P = 0.031; ßFLI→DBP = 0.082, P < 0.001 versus ßDBP→FLI = -0.006, P = 0.480 for CEMC, and ßFLI→SBP = 0.057, P < 0.001 versus ßSBP→FLI = -0.001, P = 0.727; ßFLI→DBP = 0.061, P < 0.001, versus ßDBP→FLI = -0.006, P = 0.263 for UKB. The validation study with 962 UKB participants using PDFF consistently supported these findings. In the mediation analyses encompassing 11,108 UKB participants, SBP and DBP mediated 12.2% and 5.2% of the hepatic steatosis-CVD association, respectively. The proportions were lower for ischemic heart disease (SBP: 6.1%, DBP: non-statistically significant -6.8%), and relatively stronger for stroke (SBP: 19.4%, DBP: 26.1%). In conclusion, hepatic steatosis more strongly contributes to elevated blood pressure than vice versa. Blood pressure elevation positively mediates the hepatic steatosis-CVD association, particularly in stroke compared to ischemic heart disease.

Dietary patterns and metabolic dysfunction-associated fatty liver disease in China's multi-ethnic regions.

BACKGROUND: The prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) has been rising rapidly in western China. Diet acts as an effective therapy for MAFLD. However, there has been scarce research on the association between a posteriori diet patterns (DPs) and MAFLD in this region. METHOD: We identified three a posteriori DPs which were "Sichuan Basin pattern" characterized by a high intake of fish/seafood, poultry, fresh fruit and vegetables, indicating a balanced and modern DP; the "Yunnan-Guizhou Plateau dietary pattern" characterized mainly by a high intake of animal oil and salt, indicating an agricultural and poor DP; and the "Qinghai-Tibet Plateau dietary pattern" characterized by a high intake of coarse grains, wheat products, tubers and tea, respectively, indicating a high-altitude DP. Then, we performed marginal structural models that combined logistic regression and inverse probability exposure weighting (IPEW) to examine the associations between MAFLD and these a posteriori DPs. RESULT: We found the "Yunnan-Guizhou Plateau dietary pattern" revealed stronger positive association (OR = 1.50, 95% CI 1.40-1.60) with MAFLD than that of the "Qinghai-Tibet Plateau dietary pattern" (OR = 1.21, 95% CI 1.14-1.30). In contrast, the "Sichuan Basin dietary pattern" showed no significant association with MAFLD. In the further stratified analysis, we found those above associations were stronger in ethnic minorities and rural residents than their counterparts. CONCLUSION: Our study implied the unfavourable effects of "Yunnan-Guizhou Plateau dietary pattern" on MAFLD and provided evidence that reducing the intake of oil and sodium may be optimal for MAFLD control in the multi-ethnic region in western China.

Dietary Approaches to Stop Hypertension (DASH) diet, Mediterranean diet and blood lipid profiles in less-developed ethnic minority regions.

Different from developed countries, there is a paucity of research examining how the Dietary Approaches to Stop Hypertension (DASH) and Mediterranean diets relate to lipids in less-developed ethnic minority regions (LEMR). A total of 83 081 participants from seven ethnic groups were retrieved from the baseline data of the China Multi-Ethnic Cohort study, which was conducted in less-developed Southwest China between May 2018 and September 2019. Multivariable linear regression models were then used to examine the associations of the DASH and alternative Mediterranean diet (AMED) scores, assessed by modified DASH score and AMED, as well as their components with total cholesterol (TC), LDL-cholesterol, HDL-cholesterol, TAG and TC/HDL-cholesterol. The DASH scores were negatively associated with TC, HDL-cholesterol and TAG. Comparing the highest quintiles with the lowest DASH scores, TC decreased 0·0708 (95 % CI -0·0923, -0·0493) mmol/l, HDL-cholesterol decreased 0·0380 (95 % CI -0·0462, -0·0299) mmol/l and TAG decreased 0·0668 (95 % CI -0·0994, -0·0341) mmol/l. The AMED scores were negatively associated with TC, LDL-cholesterol and HDL-cholesterol. Comparing the highest quintiles with the lowest AMED scores, TC decreased 0·0816 (95 % CI -0·1035, -0·0597) mmol/l, LDL-cholesterol decreased 0·0297 (95 % CI -0·0477, -0·0118) mmol/l and HDL-cholesterol decreased 0·0275 (95 % CI -0·0358, -0·0192) mmol/l. Although both the DASH diet and the Mediterranean diet were negatively associated with blood lipids, those associations showed different patterns in LEMR, particularly for TAG and HDL-cholesterol.