Sulfonylurea challenge test in subjects diagnosed with type 1 diabetes mellitus

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.

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.

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.

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.

These data demonstrate the feasibility of the sulfonylurea challenge test, and suggest that responder individuals may be identified.

We propose that this sulfonylurea challenge test should be explored more extensively, as it may prove useful as a clinical and scientific tool.