Insulin resistance (IR) can be optimally assessed using the euglycemic clamp, but practical clinical limitations necessitate surrogate markers. This study leveraged the Bayesian network analysis to evaluate three established IR markers: the Homeostatic Model Assessment of IR (HOMA-IR) using insulin level and fasting blood glucose (FBG), TG-Glucose (TyG) index using triglycerides (TG) and FBG, and TG-to-HDL ratio (TG/HDL ratio) using TG and high-density lipoprotein (HDL), based on the Korean National Health and Nutrition Examination Survey data (2019–2021). Our analysis revealed a sequential association pattern (TG/HDL ratio → TyG index → HOMA-IR), positioning the TyG index as a central connecting marker. The HOMA-IR exhibited strong predictive power for diabetes, while the TG/HDL ratio was most effective for assessing dyslipidemia. However, both had limited crossover utility. In contrast, the TyG index bridged this gap, demonstrating robust predictive capability for both conditions. The Markov blanket analysis illuminated the distinctive metabolic signatures of each marker: The TyG index displayed balanced glucose-lipid metabolic contributions, the HOMA-IR predominantly reflected glucose metabolism and obesity characteristics, and the TG/HDL ratio emphasized lipid metabolism. Notably, the TyG index’s predictive performance showed significant enhancement when integrated with obesity information, contrasting with the HOMA-IR’s minimal response owing to its inherent incorporation of obesity characteristics. These findings position the TyG index as a superior clinical marker, offering both comprehensive predictive capability and enhanced performance through synergistic integration with obesity measures. While each marker demonstrated reliability, the TyG index’s unique combination of versatility and scalability establishes it as an effective tool for comprehensive metabolic risk assessment.

Background: The Fibrosis-4 (FIB-4) index is widely recommended as a first-tier method for screening advanced hepatic fibrosis; however, its diagnostic performance is known to be suboptimal in patients with Type 2 diabetes mellitus (T2DM). We aim to propose a modified FIB-4, using the parameters of the existing FIB-4, tailored specifically for diabetic patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: A total of 1503 patients who underwent liver biopsy were divided into T2DM (n = 517) and non-T2DM (n = 986) groups. The model was developed using multiple regression analysis in the derivation cohort and validated in the validation cohort. Diagnostic accuracy was evaluated using the area under the receiver operating characteristic (AUC) curves. Results: Among the 1503 individuals, those with T2DM were older, more likely to be male, and had a higher prevalence of advanced hepatic fibrosis (≥F3) compared to non-T2DM individuals. Independent risk factors for advanced fibrosis in T2DM included age, AST, AST/ALT ratio, albumin, triglycerides, and platelet count. The optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index) demonstrated superior diagnostic accuracy (AUC 0.771) compared to the FIB-4 (AUC 0.735, p = 0.012). The model showed a higher negative predictive value than the original FIB-4 across all age groups in the diabetic group. Conclusions: The newly optimized FIB-4 model for T2DM with MASLD (Diabetes Fibrosis Index), incorporating a non-linear predictive model, improves diagnostic performance (AUC) and the negative predictive value in MASLD with T2DM.

INTRODUCTION: Alcohol contributes to the progression of steatotic liver disease. However, in individuals with metabolic dysfunction and alcohol-associated liver disease (MetALD), the impact of changes in drinking behavior on disease progression remains unclear. We investigated whether longitudinal changes in alcohol consumption were associated with the risk of major adverse liver outcomes (MALO) in people with MetALD. METHODS: Data were obtained from the Korean National Health Screening Program. Adults with MetALD who completed 3 screening examinations (2009–2010, 2011–2012, and 2013–2014) were included (n = 85,554). Participants were categorized by alcohol consumption trajectories: group 1 (sustained consumption), group 2 (fluctuating consumption), and group 3 (consistent reduction). The primary outcome was MALO, with cardiovascular death treated as a competing risk. Changes in cardiometabolic risk factors from baseline to the last examination were also evaluated. RESULTS: Over a median follow-up of 9.1 years, 32.9%, 34.6%, and 32.4% of participants were classified into Groups 1, 2, and 3, respectively. Groups 2 and 3 had lower MALO risks than group 1 (adjusted subdistribution hazard ratios (95% confidence intervals), 0.80 (0.71–0.91) and 0.70 (0.61–0.79), respectively; both P < 0.001). Compared with group 1, group 3 had higher rates of resolution of impaired fasting glucose, hypertriglyceridemia, and hypertension. DISCUSSION: Alcohol use in MetALD was highly dynamic, and hepatic risk was better captured using longitudinal drinking trajectories. Both intermittent and consistent alcohol reduction were associated with lower MALO risk, with a stronger association for consistent reduction. Consistent reduction was also accompanied by favorable changes in selected cardiometabolic risk factors.

Background: Alcohol contributes to the progression of steatotic liver disease. However, in individuals with MetALD, the impact of changes in drinking behavior on disease progression remains unclear. We investigated whether longitudinal changes in alcohol consumption were associated with the risk of major adverse liver outcomes in people with MetALD. Methods: Data were obtained from the Korean National Health Screening Program. Adults with MetALD who completed three screening examinations (2009–2010, 2011–2012, and 2013–2014) were included (n = 58,434). Participants were categorized by alcohol consumption trajectories: Group 1 (sustained consumption), Group 2 (fluctuating consumption), and Group 3 (consistent reduction). The primary outcome was major adverse liver outcomes. Changes in cardiometabolic risk factors from baseline to the last examination were also evaluated. Findings: Over a median follow-up of 8.1 years, 33.2% of participants were classified as Group 1, 34.8% as Group 2, and 32.0% as Group 3. After multivariable adjustment, Group 3 had a lower risk of major adverse liver outcomes than Group 1 (adjusted HR, 0.84; P = 0.032). For liver-related mortality, risk was lower in Group 2 (adjusted HR, 0.73; P = 0.023) and Group 3 (adjusted HR, 0.65; P = 0.004). Consistent alcohol reduction was accompanied by greater resolution of hypertriglyceridemia and hypertension compared with sustained consumption. Interpretation: Alcohol use in MetALD is highly dynamic, and hepatic risk is better captured using longitudinal drinking trajectories. Sustained alcohol reduction appears to confer cardiometabolic benefits, largely through improvements in hypertriglyceridemia and hypertension.