1657-P: Post–Mixed Meal Glucagon Secretion Is Not Influenced by Residual Beta-Cell Function in Type 1 Diabetes

Aims: Postprandial glucose excursions contribute to dysglycemia in type 1 diabetes (T1D). Hyperglucagonaemia may play a role but the relationship between beta and alpha-cell dysfunction together with incretin response remains unclear. We sought to elucidate this in people with established T1D with and without C-peptide.

Methods: Participants (n=29, age 38 ± 12 years, HbA1c 57 ± 9 mmol/mol, T1D duration 20 ± 13 years) with a range of postprandial urine C-peptide were recruited. A Meal Tolerance Test (MTT, 240 mL Fortisip: 360kcal, 14.4g protein, 13.92g fat, 44.16g carbohydrate) was completed after an overnight fast, maintaining normal basal insulin, without an insulin bolus. Blood samples were taken pre and 30min intervals for 180 minutes post-drink and analysed for glucose, C-peptide, glucagon, proinsulin, GLP-1 and GIP. Participants were grouped by peak C-peptide (high >200 pmol/L, low 3-200pmol/L, undetectable). [Incremental] area under the curves ([i]AUC) were compared by one way ANOVA, Spearman's correlation and multiple regression with significance accepted p≤0.05.

Results: Ten participants had high peak C-peptide (680 ± 426 pmol/L), 8 low (39 ± 34 pmol/L), and 11 undetectable. Glucagon was comparable in all groups with mean AUC 1721 ± 890 pmol/L*180min (p=0.84). Glucagon correlated with GLP-1 (r=0.81, p<0.01) and GIP (r=0.43, p=0.02) response, but not C-peptide (R=-0.10, p=0.61), proinsulin (r=-0.18, p=0.35) or proinsulin/C-peptide ratio (r=0.04, p=0.85). C-peptide predicted glucose AUC using multiple regression (R² = 44.3%, F(1, 27) = 21.4, p<0.01). C-peptide in combination with glucagon predicted glucose iAUC (R² = 41.1% F(2, 26) = 9.1, p<0.01).

Conclusion: Residual C-peptide is a predictor of MTT glucose excursions but not glucagon response in established T1D. Postprandial glucagon contributed to glucose excursion as well as correlating with incretin response. This supports altered alpha-cell phenotype in T1D, aberrantly responding to or secreting incretin.