Long-term follow-up data from two randomized lifestyle intervention trials suggest that changes in body fat distribution, particularly reductions in visceral adipose tissue, may have lasting cardiometabolic implications even after body weight is regained. A 5- and 10-year follow-up analysis of the CENTRAL and DIRECT-PLUS randomized controlled trials, published in Circulation, evaluated the long-term cardiometabolic effects of dietary interventions combined with structured physical activity. 

The original trials assessed low-fat, Mediterranean, low-carbohydrate, and polyphenol-enriched green Mediterranean dietary patterns. Of 381 eligible participants, 366 (96%) completed long-term follow-up assessments. 

Findings

• Despite complete weight regain, reductions in waist circumference and abdominal fat depots, including visceral and subcutaneous fat, remained partially preserved during long-term follow-up (false discovery rate ≤0.01 for all).
• Intrahepatic fat reductions were fully regained, while intrapancreatic fat increased beyond post-intervention levels during follow-up (false discovery rate ≤0.01 for both).
• Each 10% reduction in visceral adipose tissue during the intervention was associated with improvements in Metabolic Score for Insulin Resistance, composite cardiometabolic risk, and metabolic syndrome severity scores (all P<0.05).
• Similar favorable metabolic associations were observed with reductions in superficial subcutaneous adipose tissue and intrapancreatic fat (all P<0.05).
• Only visceral adipose tissue reduction remained independently associated with lower incident type 2 diabetes risk, with each 10% loss linked to a 28% lower risk during follow-up (hazard ratio [HR], 0.72; 95% confidence interval [CI], 0.54–0.94).

The findings suggest that lifestyle interventions may confer durable cardiometabolic benefits despite later weight regain, with visceral adipose tissue reduction remaining an important marker of long-term metabolic health.