Changes in insulin sensitivity and gut peptides 8 and 52 weeks after bariatric surgery or low-calorie diet

The endocrine consequences of weight loss by bariatric surgery (BS) and caloric restriction are not fully understood but contribute to variable improvements in insulin sensitivity and cardiometabolic health. This study compared changes in insulin sensitivity and plasma concentrations of gut peptides 8 weeks and 1 year after BS and a low-calorie diet (LCD). Nineteen female patients with obesity self-selected BS (gastric bypass [n = 5] or sleeve gastrectomy [n = 7]) or LCD (n = 7) in this parallel-arm, prospective observational study. We assessed insulin sensitivity via a two-step hyperinsulinemic-euglycemic clamp (20 and 80 mU/min/m² insulin). Plasma glucose, insulin, and gut peptides were measured around a mixed meal tolerance test (400 kcal). Visual analogue scales (VAS) were used to rate subjective appetite sensations. All assessments were conducted at baseline and after 8 weeks and 1 year of intervention. Whole-body insulin sensitivity was unchanged 8 weeks after the intervention. One year after surgery, insulin sensitivity at both 20 and 80 mU/m²/min insulin infusion doses increased with BS weight loss (-33.8% ± 1.4% body weight) but was unchanged in LCD with small weight loss (-3.7% ± 2.0% body weight). Postprandial total PYY increased more following BS while total and acylated ghrelin decreased more following BS compared to LCD. Hunger decreased and fullness increased with BS compared to LCD (p = .037; p = .010, respectively). Insulin sensitivity was improved only 1 year after BS, despite significant weight loss after 8 weeks. Changes in gut peptides after BS paralleled reduced hunger and increased fullness. Most improvements in cardiometabolic health were related to weight loss.