Insulin resistance (IR) precedes type 2 diabetes and may vary in severity and organ-specific location, influencing body composition and diabetes risk. At the European Association for the Study of Diabetes (EASD) 2025, data from 5,509 participants (53% women, mean age 54 ± 6 years, BMI 30 ± 5 kg/m²) in the Netherlands Epidemiology of Obesity (NEO) study were analyzed to examine organ-specific IR subtypes. 

Hepatic insulin resistance index (HIRI), muscle insulin resistance index (MIRI), and disposition index (DI) were used to classify participants into eight IR subtypes. During a median follow-up of 6.6 years, 283 participants developed type 2 diabetes. Subtypes characterized by low DI and hepatic IR, with or without concomitant muscle IR, carried the highest diabetes risk (HR=19.48 [9.02–42.09] and HR=20.16 [9.32–43.60], respectively). 

These subtypes also exhibited the greatest adiposity, largest waist circumference, and highest visceral and liver fat. The findings highlight the prognostic importance of hepatic IR and beta-cell dysfunction in type 2 diabetes development and suggest targeted monitoring and early interventions for high-risk metabolic profiles.