Long-term persistence of hormonal adaptations to weight loss.
Level 4 - case-series / case-control
Uncontrolled single-arm prospective interventional follow-up study
PubMed 22029981 · doi:10.1056/NEJMoa1105816
What was done
Fifty overweight or obese adults without diabetes were enrolled in a 10-week weight-loss program using a prescribed very-low-energy diet. Circulating levels of nine appetite-regulating hormones (leptin, ghrelin, peptide YY, gastric inhibitory polypeptide, glucagon-like peptide 1, amylin, pancreatic polypeptide, cholecystokinin, and insulin) and subjective appetite ratings were measured at baseline, at 10 weeks (program completion), and at 62 weeks (one year after initial weight loss).
What was found
Initial weight loss averaged 13.5 ± 0.5 kg at 10 weeks. This was accompanied by significant reductions in leptin, peptide YY, cholecystokinin, insulin (all P < 0.001), and amylin (P = 0.002), alongside significant increases in ghrelin (P < 0.001), gastric inhibitory polypeptide (P = 0.004), pancreatic polypeptide (P = 0.008), and subjective appetite (P < 0.001). At 62 weeks, significant differences from baseline remained for leptin (P < 0.001), peptide YY (P < 0.001), cholecystokinin (P = 0.04), insulin (P = 0.01), ghrelin (P < 0.001), gastric inhibitory polypeptide (P < 0.001), pancreatic polypeptide (P = 0.002), and subjective hunger (P < 0.001).
Why it matters
This study shows that hormonal adaptations favoring weight regain do not normalize within a year after weight loss, providing a physiological basis for the high relapse rate following diet interventions.
Limits
The study lacked a randomized control or weight-stable comparator group. The sample size was modest (n = 50), excluded patients with diabetes, and evaluated rapid weight loss via a very-low-energy diet, which may not generalize to slower, lifestyle-driven weight reduction. Absolute hormone levels and weight trajectory at 62 weeks were not reported in the abstract.
Cited by
- supports Fat loss reduces circulating leptin, which alongside ghrelin stimulates appetite and promotes weight regain toward a set point.