Comparison of an oral mixed meal plus arginine and intravenous glucose, GLP-1 plus arginine to unmask residual islet function in longstanding type 1 diabetes

Abstract

Residual beta cells are present in most patients with longstanding type 1 diabetes but it is unknown whether these beta cells react normally to different stimuli. Moreover a defect in proinsulin conversion and abnormal alpha cell response are also part of the islet dysfunction. A three-phase [euglycemia, hyperglycemia, and hyperglycemia þ glucagon-like peptide 1 (GLP-1)] clamp was performed in patients with longstanding type 1 diabetes. Intravenous arginine boluses were administered at the end of each phase. On another day, a mixed meal stimulation test with a subsequent intravenous arginine bolus was performed. C-peptide was detectable in a subgroup of subjects at baseline (2/15) or only after stimulation (3/15). When detectable, C-peptide increased 2.9-fold [95% CI: 1.2–7.1] during the hyperglycemia phase and 14.1-fold [95% CI: 3.1–65.2] during the hyperglycemia þ GLP-1 phase, and 22.3-fold [95% CI: 5.6–89.1] during hyperglycemia þ GLP-1 þ arginine phase when compared with baseline. The same subset of patients with a C-peptide response were identified during the mixed meal stimulation test as during the clamp. There was an inhibition of glucagon secretion (0.72-fold, [95% CI: 0.63–0.84]) during the glucose clamp irrespective of the presence of detectable beta cell function. Proinsulin was only present in a subset of subjects with detectable C-peptide (3/15) and proinsulin mimicked the C-peptide response to the different stimuli when detectable. Residual beta cells in longstanding type 1 diabetes respond adequately to different stimuli and could be of clinical benefit.