Background: The association of the severity of hepatic steatosis in metabolic dysfunction–associated fatty liver disease (MAFLD)/metabolic dysfunction–associated steatotic liver disease (MASLD) and the remission of MAFLD/MASLD with CKD occurrence is unclear. Methods and Results: The study enrolled 79 540 participants from the Kailuan cohort. Hepatic steatosis was diagnosed by ultrasound. MAFLD/MASLD was defined as hepatic steatosis combined with metabolic dysfunction and MASLD further excluded alcohol or other causes of liver disease. Chronic kidney disease (CKD) was defined as estimated glomerular filtration rate<60 mL/min per 1.73 m ² or positive proteinuria (≥1+). Hazard ratio (HR) was calculated by Cox regression models. After a median follow‐up of 12.9 years, CKD occurred in 20 465 participants. After adjusting for potential confounders, MAFLD was associated with a higher risk of CKD compared with non‐MAFLD (HR, 1.12 [95% CI, 1.09–1.16]), and this risk increased with increasing severity of hepatic steatosis ( P ‐trend<0.001). Consistent findings were observed when MASLD was used as the exposure. Compared with persistent non‐MAFLD, no statistical difference was found in the risk of CKD in MAFLD remission (HR, 1.04 [95% CI, 0.95–1.15]); however, MASLD remission still had a higher risk of CKD compared with persistent non‐MASLD (HR, 1.15 [95% CI, 1.03–1.27]). When grouped according to the prior severity of hepatic steatosis, there was no statistically significant difference in risk of CKD in mild‐MAFLD/MASLD remission compared with persistent non‐MAFLD/MASLD, but moderated/severe‐MAFLD/MASLD remission still had a higher risk. Conclusions: The risk of CKD in patients with MAFLD/MASLD increased with the severity of hepatic steatosis. Even after remission of the disease, patients with MAFLD/MASLD with prior moderate to severe hepatic steatosis still had a higher risk of CKD.

Background: The impact of long-term serum uric acid (SUA) exposure and time course of SUA accumulation on diabetes mellitus (DM) is unknown. This study aimed to evaluate the association of cumulative SUA (cumSUA) exposure and its accumulation time course with risk of DM. Methods: This prospective study included 46,434 participants without DM and underwent three examinations at 2006, 2008, and 2010. CumSUA from 2006 to 2010 was calculated, multiplying mean values between consecutive examinations by time intervals between visits. Time course of SUA accumulation was categorized as the slope of SUA versus time from 2006 to 2010, or by splitting the overall accumulation into an early (cumSUA_06-08) and late accumulation (cumSUA_08-10). Results: During 6.99 years of follow-up, we identified 2971 incident DM cases. In the fully adjusted model, a higher risk of DM was observed in participants with the highest quartile of cumSUA (hazard ratio [HR], 1.31; 95% confidence interval [CI], 1.17–1.46), cumulative burden >0 (HR, 1.23; 95% CI, 1.08–1.40), and with 6 year of hyperuricemia exposure duration (HR, 1.25; 95% CI, 1.01–1.55). When considering the time course of SUA accumulation, participants with a negative slope (HR, 1.05; 95% CI, 1.01–1.12), or combined with cumSUA ≥ median and a negative slope had elevated risk of DM (HR, 1.58; 95% CI, 1.18–2.11). Conclusions: Incident DM risk depends on cumulative exposure of SUA and time course of SUA accumulation. Early SUA accumulation resulted in a greater risk increase compared with later accumulation, emphasizing the importance of optimal SUA control early in life.

Background: Both elevated inflammation and atherogenic dyslipidemia are prominent in young-onset diabetes and are increasingly identified as biologically intertwined processes that contribute to diabetogenesis. We aimed to investigate the age-specific risks of type 2 diabetes (T2D) upon concomitant chronic inflammation and atherogenic dyslipidemia. Methods: Age-stratified Cox regression analysis of the risk of incident diabetes upon co-exposure to time-averaged cumulative high-sensitivity C-reactive protein (CumCRP) and atherogenic index of plasma (CumAIP) among 42,925 nondiabetic participants from a real-world, prospective cohort (Kailuan Study). Results: During a median 6.41 years of follow-up, 3987 T2D developed. Isolated CumAIP and CumCRP were significantly associated with incident T2D in the entire cohort and across all age subgroups. Both CumAIP and CumCRP were jointly associated with an increased risk of diabetes (P-interaction = 0.0126). Compared to CumAIP < -0.0699 and CumCRP < 1 mg/L, co-exposure to CumAIP ≥ − 0.0699 and CumCRP ≥ 3 mg/L had a significant hazard ratio (HR) [2.55 (2.23–2.92)] after adjusting for socio-demographic, life-style factors, family history of diabetes, blood pressure, renal function and medication use. The co-exposure-associated risks varied greatly by age distribution (P-interaction = 0.0193): < 40 years, 6.26 (3.47–11.28); 40–49 years, 2.26 (1.77–2.89); 50–59 years, 2.51 (2.00–3.16); 60–69 years, 2.48 (1.86–3.30); ≥ 70 years, 2.10 (1.29–3.40). In young adults (< 45 years), both exposures had a significant supra-additive effect on diabetogenesis (relative excess risk due to interaction: 0.80, 95% CI 0.10–1.50). Conclusions: These findings highlight the need for age-specific combined assessment and management of chronic inflammation and dyslipidemia in primary prevention against T2D, particularly for young adults. The clinical benefit derived from dual-target intervention against dyslipidemia and inflammation will exceed the sum of each part alone in young adults.

Background: Stroke is a common complication of hypertension, but the predictive value of metabolic syndrome parameters' variability on stroke risk in individuals with hypertension remains unclear. Therefore, our objective was to investigate the relationship between metabolic syndrome parameters' variability and the risk of total stroke and its subtypes in hypertensive patients. Methods: This prospective cohort study included 17,789 individuals with hypertension from the Kailuan study since 2006. Metabolic syndrome parameters, including waist circumference (WC), fasting blood glucose (FBG), systolic blood pressure (SBP), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG), were collected at three follow-up visits in the 2006, 2008, and 2010 surveys. We assess the variability utilizing the coefficient of variation (CV), standard deviation (SD), average real variation (ARV), and variability independent of the mean (VIM), with CV initially assessed. Participants were categorized based on the number of high-variability metabolic syndrome parameters (0, 1, 2, ≥ 3). Stroke cases were identified by reviewing medical records. The associations between variability in metabolic syndrome parameters and the risk of total stroke and its subtypes were analyzed using Cox proportional hazard regression models. Results: During a median follow-up of 9.32 years, 1223 cases of stroke were recorded. Participants with ≥ 3 high-variability metabolic syndrome parameters had an increased risk of total stroke (HR: 1.29, 95%CI 1.09–1.52), as well as an increased risk of ischemic stroke (HR: 1.31, 95%CI 1.05–1.63) compared to those without high-variability parameters. The study also examined variability in each metabolic syndrome parameter, and significant associations with an increased risk of total stroke were observed for variability in SBP (HR: 1.24, 95%CI 1.05–1.46) and HDL-C (HR: 1.34, 95%CI 1.09–1.64). Conclusions: Long-term fluctuations in metabolic syndrome parameters significantly increase the risk of total stroke, especially ischemic stroke. Maintaining low variability in metabolic syndrome parameters could benefit health, and hypertensive individuals must be regularly monitored.

Cardiovascular-kidney-metabolic (CKM) syndrome is a systemic disorder characterized by pathophysiological interactions among metabolic risk factors. We aimed to determine the prevalence of CKM syndrome and investigate the association between CKM stages and mortality in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). We extracted data on patients with MASLD from NHANES III and the Chinese Kailuan cohort, enrolling a total of 2159 and 22,865 patients, respectively. Hepatic steatosis was assessed by liver ultrasound. Participants were categorized into three groups according to CKM stages: 1, 2, and 3-4. Mortality was evaluated using the Cox proportional hazards model with or without inverse probability of treatment weighting (IPTW). In NHANES III cohort, 84.5% MASLD patients meet the criteria for CKM stage 2 or higher, and 36.9% deaths are observed. CKM stages 3-4 is an independent risk factor for liver fibrosis after adjusting for confounding factors (aOR 2.24 95% CI: 1.14-4.40, P = 0.019). By using stage 1 as a reference, an increasing trend in all-cause mortality is shown in patients with higher stages (stage 2: aHR 1.55, 95% CI 1.17-2.07, P = 0.003; stages 3-4: aHR 2.69, 95% CI 1.92-3.76, P < 0.001), as well as for cardiovascular mortality during a follow-up of 50,895.4 person-years. Moreover, patients with stages 3-4 have the highest mortality risk among different stages across most subgroups. Similar results are validated in Kailuan cohort. The majority of MASLD patients also have CKM syndrome. A significant increase in all-cause and cardiovascular mortality is associated with advancing CKM stages.