RT Journal Article
SR Electronic
T1 Pharmacokinetics and Pharmacodynamics of NPH Insulin in Type 1 Diabetes: The Importance of Appropriate Resuspension Before Subcutaneous Injection
JF Diabetes Care
JO Diabetes Care
FD American Diabetes Association
SP 2204
OP 2210
DO 10.2337/dc15-0801
VO 38
IS 12
A1 Lucidi, Paola
A1 Porcellati, Francesca
A1 Marinelli Andreoli, Anna
A1 Carriero, Ilaria
A1 Candeloro, Paola
A1 Cioli, Patrizia
A1 Bolli, Geremia B.
A1 Fanelli, Carmine G.
YR 2015
UL http://care.diabetesjournals.org/content/38/12/2204.abstract
AB OBJECTIVE Crystalline NPH insulin comes in a two-phase solution with either a solvent or a rapid-acting insulin (in premixed formulations) and needs adequate mixing for complete resuspension before injection. The aim of this study was to establish pharmacokinetics (PK) and pharmacodynamics (PD) after injection of appropriately resuspended versus nonresuspended NPH insulin.RESEARCH DESIGN AND METHODS PK and PD were assessed after subcutaneous injection of NPH insulin 0.35 units/kg at steady state by pen either resuspended (R+, tipping of insulin pen 20 times) or nonresuspended (pen maintained in fixed position either horizontally [R- horizontal] or vertically with tip up [R- up] or tip down [R- down]). Eleven subjects with type 1 diabetes (age 31.5 ± 12 years, diabetes duration 17.5 ± 7.7 years, BMI 22.9 ± 1.5 kg/m2, A1C 7.2 ± 0.4% [55.2 ± 4.4 mmol/mol]) were studied (euglycemic clamp) with a randomized crossover design.RESULTS Compared with resuspended NPH insulin (R+), nonresuspended NPH insulin resulted in profound PK/PD differences with either reduced (R- horizontal and R- up) or increased (R- down) plasma insulin concentrations [FIRI_AUC(0–end of study) (free immunoreactive insulin area under the concentration-time curve between 0 and end of study)] and PD activity [glucose infusion rate (GIR)_AUC(0–end of study)] (all P < 0.05). Duration of NPH insulin action was shorter in R- up (9.4 ± 1.7 h) but longer in R- down (15.4 ± 2.3 h) compared with R+ (11.8 ± 2.6 h) (P < 0.05). Within-subject variability (percent coefficient of variation) among studies was as high as 23% for PK [FIRI_AUC(0–end of study)] and 62% for PD [GIR_AUC(0–end of study)].CONCLUSIONS Compared with resuspended NPH insulin, lack of resuspension profoundly alters PK/PD and may importantly contribute to day-to-day glycemic variability of type 1 diabetes.