OBJECTIVE: To assess b-cell function and insulin sensitivity following improvement in glycemic control in severely insulin-resistant @entity1 with poorly controlled @entity2175 ( @entity2175 ). METHODS: A subset of @entity1 in a 24-week, open-label, randomized trial comparing thrice-daily (n = 14/162) versus twice-daily (n = 11/163) @entity1 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; @entity6 duration, 13.6 years; body mass index, 38.8 kg/m(2); 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 @entity413 (AUCC-peptide/AUC @entity413 ) 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. b-Cell function significantly improved after 24 weeks of U-500R therapy in combined treatment groups. The AUCC-peptide/AUC @entity413 increased 34.0% (ratio of least-squares geometric mean, 1.34; 95% confidence interval, 1.18 to 1.52; P = .0001). Integral of total insulin secretion rate increased from 27.0 to 33.7 nmol/m(2), and @entity413 sensitivity improved from 18.3 to 24.0 pmol/min/m(2)/mM (both, P = .02). Matsuda index improved from 0.8 to 1.3 (P = .008). CONCLUSION: Despite long-standing @entity6 and poor glycemic control at baseline, functional recovery of b-cells was observed with improved glycemic control in these severely insulin-resistant @entity1 with @entity2175 , possibly due to alleviation of glucotoxicity. ABBREVIATIONS: AUC = area under the curve BID = twice daily HbA1c = glycated hemoglobin ISR = insulin secretion rate LSM = least-squares mean MMTT = mixed meal tolerance test PG = plasma @entity413 @entity2175 = @entity2175 TDD = total daily dose TID = thrice daily U-500R = @entity1 regular U-500 insulin.

OPTIMIZED XXXX REGULAR U-500 INSULIN TREATMENT IMPROVES b-CELL FUNCTION IN SEVERELY INSULIN-RESISTANT @entity1 WITH LONG-STANDING TYPE 2 DIABETES AND HIGH INSULIN REQUIREMENTS.

@entity1 :: ('9606', 'Species') :: ['human', 'patients'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity2175 :: ('MESH:D003924', 'Disease') :: ['type 2 diabetes', 'T2D']
@entity1 :: (9606,Species) :: ['HUMAN']
