235-LB: Time Course of Pancreatic Alpha-Cell Function in Fulminant Type 1 Diabetes

Aim: We aim to investigate the time course of changes in pancreatic alpha-cells function in patients with newly-onset fulminant type 1 diabetes (FT1D).

Methods: Glucagon and C-peptide concentrations were determined in response to 100g steamed bread meal tests (SBMT) in 6 patients with newly-onset FT1D. SBMT were taken every 3 months thereafter until 6 months for 1 FT1D patient and 12 months later for 2 FT1D patients. The area under curve of C-peptide (tAUC_c-peptide) and the incremental area under curve of glucagon (iAUC_glucagon) were calculated with 0min glucagon as baseline during SBMT.

Results: (1) At the onset of disease, tAUC_c-peptide in FT1D patients was significantly lower than that of typical autoimmune type 1 diabetes [(217.04 ± 67.47) vs. (1762.00 ± 255.84) pmol/L*h, P<0.0001]. The iAUC_glucagon of 4 FT1D patients were higher than patients with typical autoimmune type 1 diabetes [(21.55±8.88) pmol/L*h vs. (6.72±2.92) pmol/L*h, P=0.006], while iAUC_glucagon of 2 FT1D patients were lower [1.09, 3.11 pmol/L*h respectively]. And iAUC_glucagon of age-matched healthy control [ -(13.16±7.68) pmol/L*h] was much lower. (2) Glucagon secretion in FT1D patients conversely decreased after 12 months of diagnosis, even as early as 6 months. After 6 months of diagnosis, tAUC_c-peptide of the FT1D patient did not decrease (456 vs. 692.1 pmol/L*h), while iAUC_glucagon drop from 1.09 to (-4.11) pmol/L*h. After 12 months of diagnosis, with islet beta-cells function completely absent, the iAUC_glucagon of 2 FT1D patients were 13.64 vs. 12.34 pmol/L*h, 16.52 vs. (-19.42) pmol/L*h at the onset of diabetes and 12 months later respectively.

Conclusions: The opposing directions of abnormal glucagon and C-peptide secretion support the dysregulated alpha-cells function in newly-onset FT1D patients. The impaired alpha-cells function may recover in the time course of disease.