Visceral Fat Loss Confers 28% Lower 10-Year Diabetes Risk Independent of Weight Regain in CENTRAL/DIRECT-PLUS Follow-Up

The FIT project achieved 96% retention and repeated 3T-MRI quantification of visceral, deep-subcutaneous, superficial-subcutaneous, hepatic, and pancreatic fat depots in 325 participants originally randomized to low-fat, Mediterranean, low-carbohydrate, or green-Mediterranean diets plus exercise. At decade follow-up, mean body weight had returned to baseline while waist circumference and visceral fat remained 8-12% below baseline values; liver fat normalized and pancreatic fat rose above baseline. These depot-specific trajectories decoupled from overall adiposity and tracked with sustained improvements in HOMA-IR and metabolic syndrome severity scores. The 28% risk reduction per 10% visceral fat decrement parallels the legacy effect observed in the Diabetes Prevention Program, where lifestyle-induced changes in insulin sensitivity persisted years after intervention cessation, yet here the signal is localized to visceral rather than total weight change. This finding challenges the prevailing clinical assumption that weight regain nullifies prior lifestyle benefits and suggests visceral adipose tissue may retain an epigenetic or inflammatory memory. Future trials should test whether repeated, shorter visceral-fat-targeted interventions (e.g., time-restricted green-Mediterranean feeding) can compound this legacy effect and whether MRI-guided visceral fat thresholds outperform BMI or waist circumference for long-term risk stratification.