Impact of weight loss on GLP-1, glucagon and oxyntomodulin secretion in patients with obesity and type 2 diabetes

BACKGROUND : The effect of glucagon on metabolic processes is ambiguous: on the one hand, an excess of this hormone in the postprandial period increases glycemia, on the other hand, it can contribute to weight loss. In this regard, it is important to assess the secretion of the natural glucagon/glucagon-like peptide-1 coagonist oxyntomodulin in obese individuals with or without type 2 diabetes (T2D). AIM : To investigate the secretion levels of GLP-1, glucagon, and the GLP-1/glucagon coagonist oxyntomodulin in patients with obesity, with or without T2D, during the weight loss process after bariatric surgery. MATERIALS AND METHODS : The study involved participants with morbid obesity, with or without T2D, all of whom underwent bariatric surgery. Prior to the procedure, and then at 3 and 6 months post-surgery, the patients participated in hyperinsulinemic euglycemic clamp tests and OGTT. During these assessments, glucose, glucagon, GLP-1, and oxyntomodulin levels were measured at 0, 30, and 120 minutes. RESULTS : The research included 44 obese patients without T2D and 42 with T2D. Baseline characteristics, including age, height, weight, BMI, waist circumference, and hip circumference, did not show significant differences between the two groups. Patients without T2D showed a lower degree of insulin resistance, a lower glucagon level, and greater preservation of GLP-1 secretion. Additionally, these patients initially exhibited higher levels of oxyntomodulin compared to those with T2D (area under the curve 2.08 [1.61; 2.50] ng/ml*h vs 1.64 [1.07; 1.78] ng/ml*h , p<0.00005). Following weight loss, oxyntomodulin secretion levels rose in both groups (in the T2DM (-) group: 2.35 [1.9; 3.28] ng/ml*h at 3 months, 2.55 [2.02; 3.35] ng/ml*h at 6 months, p<0.00001; in the T2DM (+) group: 2.27 [1.95; 2.61] ng/ml*h at 3 months; 2.4 [1.99; 2.72] ng/ml*h at 6 months, p<0.00001) with no significant intergroup differences at 3 and 6 months after ­surgery. CONCLUSION : Baseline oxyntomodulin levels were significantly higher in patients with normal carbohydrate metabolism than in patients with type 2 diabetes and increased equally in both groups at 3 and 6 months after bariatric intervention. These results may indicate potential protective functions of oxyntomodulin, but further studies are needed.