The threshold shift paradigm of obesity: evidence from surgically induced weight loss.

BACKGROUND The high prevalence of obesity has called attention to the near-intractable problem of sustained weight reduction and its underlying mechanisms. With diet-induced weight loss, achieved body weight is closely related to initial body weight. OBJECTIVE The objective was to compare the relation between initial and achieved body mass index (BMI) in patients treated with diet-induced weight loss or bariatric surgery. DESIGN We analyzed data from a cohort of 223 healthy individuals who lost a mean (±SD) of 5 ± 3 kg body weight over 3 y by diet (diet group) and data from 182 obese individuals [BMI (in kg/m(2)) ≥35] who had lost an average of 47 ± 17 kg 1 y after Roux-en-Y gastric bypass (a restrictive procedure; n = 71) or biliopancreatic diversion (a malabsorptive procedure; n = 111) (surgery group). RESULTS In the diet group, final BMI was strongly related to initial BMI (r = 0.96, P < 0.0001). By multivariate analysis, the decrease in BMI at 3 y was age independent and was predicted only by initial BMI and sex (both P < 0.0001). Strikingly, final BMI was also strongly related to initial BMI (r = 0.67, P < 0.0001) in the surgery group, irrespective of the type of operation. The surgically induced decrease in BMI was predicted by age (P = 0.0002) and initial BMI (P < 0.0001). In 110 surgery patients, serum leptin concentrations decreased from 39 ± 16 to 10 ± 5 ng/mL after surgery (P < 0.0001) and were correlated with BMI both before and after surgery, but the slope of the relation was significantly (P < 0.01) flatter after surgery. CONCLUSION The strong predictivity of initial BMI for achieved BMI observed even when voluntary control of energy intake is interfered with through diverse anatomical rearrangements of the gastrointestinal tract supports the concept of a weight "threshold" paradigm: in the obese, anabolic responses are triggered by adiposity-related signals at a higher threshold, which leads to defense of a higher body weight.