Glucose Metabolism Parameters and Post-Prandial GLP-1 and GLP-2 Release Largely Vary in Several Distinct Situations: a Controlled Comparison Among Individuals with Crohn's Disease and Individuals with Obesity Before and After Bariatric Surgery.

BACKGROUND: This study aims to compare the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 among individuals with Crohn's disease (CD), obese individuals before and after bariatric surgery, and healthy controls. METHODS: This an exploratory cross-sectional study that involved five groups of patients (two groups of individuals with CD-active and inactive), bariatric patients (pre- and post-surgery, who were their own controls), and a distinct separated control group of healthy volunteers. C-reactive protein (CRP) levels and the post-prandial curves of glucose, insulin, GLP-1, and GLP-2 curves were assessed and compared. RESULTS: The pre-RYGB group presented significantly higher levels of CRP than the post-RYGB (p = 0.001) and the control group (p = 0.001). The inactive CD group presented a higher post-prandial GLP-1 area under the curve (AUC) than the pre-RYGB group (p = 0.009). The post-RYGB group presented significantly higher AUCs of GLP-2 than the pre-RYGB group (p < 0.0001), both inactive and active CD groups (p < 0.0001 in both situations), and the control group (p = 0.002). The pre-RYGB group presented a significantly higher AUC of glucose than the post-RYGB (p = 0.02) and both active and inactive CD groups (p = 0.019 and p = 0.046, respectively). The pre-RYGB group presented a significantly higher AUC of insulin than the control (p = 0.005) and both CD groups (p < 0.0001). CONCLUSIONS: Obesity is associated with an inflammatory state comparable to the one observed in CD; inflammation may also be enrolled in the blockade of GLP-2. CD individuals present a more incretin-driven pattern of glucose metabolism, as a way to prevent hypoglycemia and compensate the carbohydrate malabsorption and GLP-2 blockade.

Association of insulin resistance and GLP-2 secretion in obesity: a pilot study.

OBJECTIVE: The objective of this pilot study was to determine whether glugagon-like peptide 2 (GLP-2) secretion relates to insulin sensitivity (IS) in obese subjects. SUBJECTS AND METHODS: Twenty four obese subjects [body mass index (BMI) 40.0 ± 3.0 kg/m² (mean ± standard deviation)] were included, nine of which were male, age 43 ± 8 years. Twelve subjects had type 2 diabetes, all treated with oral anti-diabetic agents only. The subjects were submitted to standard meal tolerance test (MTT) for dosage of the curves: glucose, insulin, and GLP-2. Insulin sensitivity was measured by HOMA-IR, and OGIS was derived from the MTT. Spearman linear correlations and partial correlations were obtained. RESULTS: There was an inverse relationship between the GLP-2 secretion and IS: HOMA-IR correlated with GLP-2 AUC (R = 0.504; p = 0.012), and OGIS correlated with GLP-2 incremental AUC (R = -0.54; p = 0.054). The correlation persisted after controlling for BMI. CONCLUSION: We found an association of GLP-2 secretion and insulin resistance (IR). The understanding of the underlying mechanisms may provide future directions in the pharmacological manipulation of incretins, and in the treatment of obesity and related metabolic disorders.