1917-P: Alpha-Cell Function in Patients with Type 1 Diabetes Is Compromised with Different Levels of Residual C-Peptide

Objective: It is poorly understood α-cell function changes to respond to the different detectable C-peptide levels in patients with type 1 diabetes (T1D). This study aims to investigate the relationship between glucagon secretion and declining β-cell function in patients with T1D.

Methods: Eighty-seven subjects [68, autoimmune type 1 diabetes (T1AD); 4, fulminant type 1 diabetes (FT1D); 15 healthy controls] were enrolled. All participants underwent a 100g steamed bread meal tests (SBMT). T1AD patients were divided into C-peptide negative (CPN), C-peptide middle (CPM) and C-peptide high (CPH) group based on peak C-peptide levels. Both fasting and postprandial of glucose, C-peptide and glucagon were measured. Glucagon among groups were compared by a linear mixed-effects model. The relationship between C-peptide, glucose and glucagon responses was evaluated by regression analysis.

Results: At baseline, fasting glucagon concentrations were comparable between CPN, CPM and CPH group (F=0.099, P=0.906). After SBMT, 180min-glucagon in CPN group were higher than in CPM (P=0.004) and in CPH group (P<0.001). The iAUC_30-180 of glucagon was lower in CPH than in CPN (P=0.001) and in CPM group (P=0.034), whereas the iAUC_{0-30 glucagon} did not differ among CPN, CPM and CPH group (F=1.246, P=0.295). The same results were observed in iAUC of glucagon/glucose. After adjustment for age, BMI and diabetes duration, the iAUC_{30-180 glucagon} in T1AD was inversely related to peak C-peptide and positively related to peak glucose levels (R_adj²=0.315, P<0.001); however, the iAUC_{0-30 glucagon} in T1AD was only positively related to 30min-glucose (R_adj²=0.466, P<0.001).

Conclusions: This study demonstrates α-cell function in patients with T1D are compromised with different levels of residual C-peptide. Glucose is also a contributor factor for postprandial hyperglucagonemia.