It remains unclear which metabolic changes are solely attributable to WL and which also involve WL-independent changes.<h4>Objective</h4>The objective of this study was to quantify changes in the adiponectin/leptin ratio and IGF binding protein 2 (IGFBP-2), both markers of metabolic disease.<h4>Methods</h4>Adults with body mass index ≥35 kg/m<sup>2</sup> underwent a 12-week 800 kcal/day low-calorie diet (LCD; n = 20), sleeve gastrectomy (n = 18), or Roux-en-Y gastric bypass (n = 10) and were studied at baseline [time 1(T1)], early weight loss [time 2 (T2)], and 1 year [time 3 (T3)]. The gene discussed is IGFBP2; the disease is Other metabolic disease.