Dextrose-Sulfonylurea Challenge As a Screening Test for Monogenic Diabetes in Patients Diagnosed with Type I Diabetes

Presentation Number: LB SAT 83
Date of Presentation: April 1st, 2017

Aurelia Christine Holland Wood*1, Bess Adkins Marshall2, Maria S. Remedi3 and Colin Nichols Nicols3
1Washington University in St. Louis, St Louis, MO, 2Washington University in St. Louis, Saint Louis, MO, 3Washington University in St. Louis, St. Louis, MO


Neonatal and MODY subtypes of monogenic diabetes due to mutations in ABCC8, KCNJ11, HNF1A and HNF4can often be treated with sulfonylurea (SU). The SEARCH for Diabetes in Youth study confirmed most patients with monogenic diabetes are misdiagnosed with Type I Diabetes (TIDM) and treated with insulin (1,2). In this study monogenic diabetes was found in 8% of antibody negative patients with presumed Type 1 diabetes, 94% of which were new diagnoses, representing 1.2% of the entire SEARCH study group, congruent with other estimates of the frequency of MODY. While genetic screening may isolate some individuals with mutations in recognized genes, there is no evidence that family history or fasting C-peptide increase pre-test probability for diagnosis of monogenic diabetes (1). In addition, genetic testing is expensive, and though efforts have been made to improve the yield of genetic testing and cost-benefit ratio, standardized methods do not yet exist (3).

To evaluate differential C-peptide response to SU and hyperglycemia as indication of clinically significant β–cell excitation defects, we developed a dextrose-SU challenge. We postulate that negative response to hyperglycemia with positive response to sulfonylurea indicates presence of a genetic defect in glucose-stimulated insulin secretion.

A single 240-minute fasting dextrose-SU challenge was performed on 27 pediatric subjects with TIDM treated with insulin, who had no evidence of cardiac or renal disease. Participation was not precluded by diabetes antibody status. Blood glucose (BG) and C-peptide were obtained at 20, 10, and 0 minutes prior to a 0.5 g/kg IV dextrose bolus (maximum dose 20 g), and at 3, 5, 10, and 20 minutes after dextrose. A single weight-based dose of glipizide was given (0.3 mg/kg, max 15mg if < 50 kg; 40 mg if > 50 kg) and glucose and C-peptide were obtained until study conclusion.

Most subjects (n=20) maintained undetectable C-peptide before and after both dextrose and SU (<0.1 ng/mL). Seven subjects (48 ±1.79 months since diagnosis) showed marginal C-peptide response to dextrose (ΔC-peptide from baseline 0.03 ± 0.03 ng/mL), with increased response after SU (peak 0.37 ± 0.32 ng/mL, ΔC-peptide after SU 0.15 ± 0.09 ng/mL), suggesting islets may show modest but specific response to SU in TIDM years after diagnosis. We previously reported a patient with TIDM who showed no C-peptide response to dextrose and an unexpected increase in C-peptide with significant hypoglycemia in response to SU, suggestive of robust excitation-secretion response (4). This suggests the challenge may serve to elicit and stratify C-peptide response to SU, assist clinicians in categorizing residual beta cell function, support screening for monogenic diabetes, and increase consideration of SU therapy for appropriate patients.


Nothing to Disclose: ACHW, BAM, MSR, CNN