2026/04/20 by TALIA A. HITT, Andrea Kelly, Darko Stefanovski +9 · 1 voice
Medicine · #Cardiovascular Disease and Adiposity #Diabetes, Cardiovascular Risks, and Lipoproteins #Growth Hormone and Insulin-like Growth Factors
paper · doi:10.2337/dc25-2976
openalex publication_date 2026/04/20 · openalex created_date 2026/04/21 · openalex updated_date 2026/07/22
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.