OPTIMIZED HUMAN REGULAR U-500 INSULIN TREATMENT IMPROVES β-CELL FUNCTION IN SEVERELY INSULIN-RESISTANT PATIENTS WITH LONG-STANDING TYPE 2 DIABETES AND HIGH INSULIN REQUIREMENTS.

ABSTRACT Objective: To assess β-cell function and insulin sensitivity following improvement in glycemic control in severely insulin-resistant patients with poorly controlled type 2 diabetes (T2D). Methods: A subset of patients in a 24-week, open-label, randomized trial comparing thrice-daily (n = 14/162) versus twice-daily (n = 11/163) human regular U-500 insulin (U-500R) underwent mixed meal tolerance testing at baseline and endpoint. Baseline characteristics were similar between treatment groups (combined means: age, 54.0 years; diabetes duration, 13.6 years; body mass index, 38.8 kg/m2; glycated hemoglobin [HbA1c], 8.3%; U-100 insulin dose, 287.6 units/day, 2.6 units/kg/day). Primary outcome measure was ratio of area under the curve (AUC) for C-peptide to glucose (AUCC-peptide/AUCglucose) at 24-week endpoint. Results: Change from baseline HbA1c, daily U-500R dose, and weight were −1.17% (P = .0002), +80.8 units (P = .0003), and +5.9 kg (P = .33), respectively. β-Cell function significantly improved aft...