Sulfonylurea challenge test in subjects diagnosed with type 1 diabetes mellitus

Background: Patients with early onset diabetes because of defects in glucose-stimulated insulin secretion (GSIS) may respond better to sulfonylureas than insulin treatment. Such patients include those with monogenic disorders, who can be differentiated from autoimmune type 1 diabetes mellitus (T1DM) by genetic testing. Genetic testing is expensive and unknown defects in GSIS would not be diagnosed. Aims: We propose a sulfonylurea challenge test to identify patients who have been clinically diagnosed with T1DM, but those who maintain a preferentially sulfonylurea-responsive insulin secretion. Materials & Methods: A total of 3 healthy controls, 2 neonatal diabetes mellitus (NDM) subjects, 3 antibody-positive (Ab+T1DM), and 12 antibody-negative (Ab−T1DM) subjects with type 1 diabetes, were given an intravenous bolus of glucose followed by an oral dose of glipizide. Results: Healthy controls showed a robust C-peptide increase after both glucose and glipizide, but NDM subjects showed a large increase in C-peptide only following glipizide. As expected, 2 of 3 Ab+T1DM, as well as 11 of 12 Ab−T1DM showed no response to either glucose or glipizide. However, 1 Ab−T1DM and 1 Ab+T1DM showed a small C-peptide response to glucose and a marked positive response to glipizide, suggesting defects in GSIS rather than typical autoimmune diabetes. Discussion: These data demonstrate the feasibility of the sulfonylurea challenge test, and suggest that responder individuals may be identified. Conclusions: We propose that this sulfonylurea challenge test should be explored more extensively, as it may prove useful as a clinical and scientific tool.