Background:

Bariatric surgery creates anatomical changes that substantially alter nutrient delivery to the gut, leading to major physiological effects on glucose regulation. Although glucose homeostasis often improves after surgery, including remission of type 2 diabetes, the altered nutrient flow can also disrupt the normal feedback relationship between plasma glucose and insulin secretion. This impaired β-cell regulation can cause an exaggerated early postprandial glucose rise followed by excessive insulin release, predisposing some individuals to postprandial hyperinsulinaemic hypoglycaemia. Several strategies have been proposed to mitigate these effects, including pharmacotherapy and dietary modifications. Given their distinct mechanisms, the aim of this secondary analysis was to compare the effectiveness of three acute interventions on improving postprandial glucose homeostasis and β-cell function in people who have previously undergone bariatric surgery, to better understand their relative contributions. 

Methods:

Data were pooled from three similarly designed acute, randomised, cross-over trials (n=38, BMI=37.9±10.2 kg/m², age=54.9±9.9 years, sex=31F). Each trial was approved by an HRA research ethics committee (REC ref: 20/YH/0123, 20/YH/0339, 20/YH/0177). Each trial included two visits (treatment and control). Treatments included 300mg canagliflozin (CANA) or 28g brazil nuts (NUTS) consumed 30 minutes before a mixed-meal, or 2g salt (SALT) consumed with a mixed-meal. Controls were 100ml water 30 minutes before the mixed-meal for CANA and NUTS, and the same meal without added salt for SALT. Blood samples were collected over 3 hours to assess plasma glucose, insulin, C-peptide, and total glucagon-like peptide-1 (GLP-1). C-peptide deconvolution was performed to evaluate β-cell function parameters (insulin secretion rate, potentiation ratio and insulin clearance). Generalised estimated equations were performed with β-cell function parameters as dependent variables, and treatment (intervention or control) and trial (CANA, NUTS, SALT) as predictor variables. The model assessed the main effect of treatment and trial and their interaction (treatmentXtrial). If a significant interaction term was observed, data were then stratified by trial.

Results:

A reduction in early glucose response (-5.9% in AUC_{0-30 mins}, P=0.004), insulin secretion rate (P=0.002), insulin potentiation ratio (P=0.001) and a 10.4% increase in basal insulin clearance (P=0.047) were observed in response to acute intervention (treatment main effect). CANA was the most effective intervention for improving mean postprandial glucose and insulin, mean insulin clearance and early (AUC_{0-30 mins}), and overall (AUC_{0-180 mins}), insulin and glucose response, treatmentXtrial P<0.05. NUTS increased basal insulin secretion rate by 10.9±4.3% and decreased insulin potentiation ratio by 44.4±10.2%, and impacted these parameters to a greater extent than SALT and CANA (P<0.05). SALT did not out-perform CANA or NUTS on any parameter.

Conclusions:

Among the interventions investigated, 300mg of canagliflozin was the most effective for improving postprandial β-cell function and glucose homeostasis. In contrast, consuming a portion of brazil nuts prior to a mixed-meal increased basal insulin secretion rate and was more effective in lowering the insulin potentiation ratio throughout the entire postprandial period, consistent with the effect of canagliflozin acting predominantly in the early postprandial phase. These findings could suggest potential complementary effects, and future research could explore how pharmacological and dietary strategies might be combined to optimise postprandial glucose regulation in individuals following bariatric surgery.