Metabolic dysfunction–associated steatotic liver disease (MASLD) affects the majority of individuals with diabetes and severe obesity, and is one of the most common indications for liver transplantation in the U.S. Emerging evidence underscores the synergistic and detrimental impact of alcohol and metabolic disease on liver and overall health. In 2023, the nomenclature for steatotic liver disease was revised to include a new subcategory known as MetALD (metabolic dysfunction– and alcohol-associated liver disease), which acknowledges alcohol use as a cofactor in liver injury alongside metabolic risk factors. This review offers key insights into the role of alcohol use as both a direct hepatotoxin and an indirect contributor to insulin resistance, dyslipidemia, and obesity. Notably, even light-to-moderate alcohol intake may hasten MASLD progression to cirrhosis and hepatocellular carcinoma, especially in individuals with existing metabolic disease, and can worsen cardiovascular disease risk. MetALD is associated with increased all-cause, cancer-related, and liver-related mortality in comparison with MASLD, reinforcing the importance of accurate alcohol assessment in managing diabetes and obesity. Diagnosis now requires stratifying alcohol use and integrating tools such as the Alcohol Use Disorders Identification Test (AUDIT) questionnaire and phosphatidylethanol testing. The caveats and use of these tools in clinical practice are discussed. Management strategies for MASLD focus on lifestyle changes, weight loss, and medications such as glucagon-like peptide 1 receptor agonists, with emerging evidence suggesting that these agents may also reduce alcohol consumption. However, treatment data on MetALD are limited. This review offers practical guidance for health care professionals on how to integrate alcohol use into existing, recommended MASLD care pathways.

OBJECTIVE South Asian individuals are at elevated diabetes risk attributed to insulin resistance, insulin deficiency, and ectopic fat. The CHARISMA study compared metabolic mechanisms in South Asian, White, and African American adolescents and young adults (AYAs) to investigate early diabetes risk in South Asian individuals. RESEARCH DESIGN AND METHODS AYAs aged 12–21 years with a BMI ≥23 kg/m2 or ≥80 percentile underwent MRI/MRS to quantify fat; OGTT with minimal modeling to calculate insulin sensitivity (Si), AUC insulin secretory rate (ISR), and disposition index (DI); DXA; and glucose-potentiated arginine stimulation test. RESULTS South Asian AYAs (n = 53, median [interquartile range] age 20.3 [18.9, 21.4] years) compared with White (n = 53, 19.1 [17.6, 20.8] years) and African American (n = 49, 18.8 [17.7, 20.5] years) AYAs (P = 0.02) of similar sex, pubertal stage, and BMI-Z had higher visceral fat on MRI (P < 0.001 vs. White; P = 0.009 vs. African American) and liver fat on MRS (P < 0.001 vs. both). South Asian AYAs had lower Si (P = 0.006) and higher dynamic AUC-ISR (P = 0.003) vs. White AYAs, higher total and static AUC-ISR vs. both White and African American AYAs (P < 0.001), and lower dynamic DI vs. African American AYAs (P = 0.039). South Asian AYAs had lower insulin clearance than White (P = 0.027) and African American (P = 0.007) AYAs. First-pass hepatic insulin extraction was lower in African American than South Asian (P < 0.0001) and White (P = 0.027) AYAs. Group differences in Si, dynamic AUC-ISR, and dynamic DI lost significance when visceral or liver fat was added to models, but higher total and static AUC-ISR in South Asian AYAs persisted. CONCLUSIONS Compared with White and African American AYAs, South Asian AYAs have higher visceral and liver fat. These findings, along with lower Si and dynamic DI, suggest elevated metabolic risk in South Asian individuals, even at young ages. Higher total and static phase insulin secretion in South Asian AYAs may precede insulin deficiency, reported in adults.