The Case for Intravenous Arginine Stimulation In Lieu of Mixed-Meal Tolerance Tests as Outcome Measure for Intervention Studies in Recent-Onset Type 1 Diabetes

• MMTT, mixed-meal tolerance test

Residual β-cell function in patients with type 1 diabetes has been generally determined by C-peptide response to stimulation by a liquid mixed-meal tolerance test (MMTT) or intravenous glucagon (1). Early trials assessed benefits of therapy by frequency and duration of the clinical remission phase in which minimal or no exogenous insulin was needed to maintain euglycemia (reviewed in 2). What is now needed is the most sensitive, and not necessarily the most physiologic measure, so that any improvement in β-cell function during a clinical trial can be detected. Both the MMTT and the intravenous glucagon test have practical limitations. The MMTT takes 2–4 h to complete, and the stimulus is subject to variations in gastrointestinal absorption, while the intravenous glucagon test often invokes nausea.

In contrast, the use of intravenous arginine to stimulate and measure β-cell secretion takes only a few minutes to perform, circumvents gastrointestinal variation, and is clinically well tolerated. In addition, responses to this nonglucose secretagogue have been demonstrated to persist after the diagnosis of diabetes at a time when responses to glucose are gone (3–6). Our goal was to determine whether arginine-stimulated C-peptide could be used in lieu of MMTT as an outcome measure for intervention studies in recent-onset type 1 diabetes.