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

TL;DR

This study shows that residual beta cells in long-term type 1 diabetes patients can respond to various stimuli, suggesting potential for clinical benefit.

Contribution

The study introduces an oral mixed meal plus arginine as an effective alternative to traditional methods for detecting residual beta cell function.

Findings

C-peptide levels increased significantly during hyperglycemia and GLP-1 + arginine phases.

An oral mixed meal plus arginine identified residual beta cell function as effectively as a glucose clamp.

Glucagon secretion was inhibited during the glucose clamp regardless of beta cell function.

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 + 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 + GLP-1 phase, and 22.3-fold [95% CI: 5.6–89.1] during hyperglycemia + GLP-1 + 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.

NEW & NOTEWORTHY If beta cell function is detectable, the beta cells react relatively normal to the different stimuli except for the first phase response to intravenous glucose. An oral mixed meal followed by an intravenous arginine bolus can identify residual beta cell function/mass as well as the more commonly used glucose potentiated arginine-induced insulin secretion during a hyperglycemic clamp.

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