Hormonal adaptations to weight loss: Responses to an oral glucose load 4 weeks after obesity surgery and low-energy diet.

Aims: In addition to weight loss, obesity surgery (OS) leads to metabolic improvements that seem at least partly independent of weight loss and are also mediated by various endocrine pathways and the brain. For the first time, we compared the short-term effects of weight loss achieved by either OS or a low-energy diet (LED) on several hormonal systems, at fasting and upon an oral glucose challenge.

Materials and methods: This study presents sub-analyses from a randomized controlled trial including 24 participants with obesity but without diabetes (BMI 35-45 kg/m²), randomized 2:1 to either OS or 4-week LED leading to comparable weight loss. Circulating levels of gut, pituitary, adrenal, thyroid hormones, glucagon, insulin-like growth factor-1 and sex hormone-binding globulin were measured at baseline and 4 weeks after either intervention, both at fasting and during an oral glucose tolerance test (OGTT).

Results: At 4 weeks, similar weight loss was achieved for the two interventions (7.7 for OS vs. 7.4% for LED). glucagon-like peptide-1 and peptide YY secretion during the OGTT increased after OS (p < 0.001 for OGTT_AUC for both hormones), but not LED, while glucagon secretion remained unaffected. Adrenocorticotropin, cortisol and prolactin levels during OGTT were increased after OS (p = 0.04, p < 0.001, p = 0.002, respectively), while parathyroid hormone levels were decreased (p = 0.007). Fasting triiodothyronine levels were reduced after OS (p = 0.01). Fasting sex hormone-binding globulin levels decreased after both interventions (p < 0.01).

Conclusion: Rapid and extensive hormonal changes occur after OS, but not LED, despite similar weight loss. Of note, few differences were seen in the fasting state, whereas multiple endocrine pathways were affected during the oral glucose challenge. The findings suggest altered responses to oral glucose after OS in several hypothalamus-pituitary endocrine axes and peripheral endocrine glands.