PMID- 25524950
OWN - NLM
STAT- MEDLINE
DCOM- 20150911
LR  - 20181202
IS  - 1935-5548 (Electronic)
IS  - 0149-5992 (Linking)
VI  - 38
IP  - 3
DP  - 2015 Mar
TI  - Pharmacokinetics and pharmacodynamics of insulin glargine given in the evening as 
      compared with in the morning in type 2 diabetes.
PG  - 503-12
LID - 10.2337/dc14-0649 [doi]
AB  - OBJECTIVE: To compare pharmacokinetics (PK) and pharmacodynamics (PD) of insulin 
      glargine in type 2 diabetes mellitus (T2DM) after evening versus morning 
      administration. RESEARCH DESIGN AND METHODS: Ten T2DM insulin-treated persons 
      were studied during 24-h euglycemic glucose clamp, after glargine injection (0.4 
      units/kg s.c.), either in the evening (2200 h) or the morning (1000 h). RESULTS: 
      The 24-h glucose infusion rate area under the curve (AUC0-24h) was similar in the 
      evening and morning studies (1,058 +/- 571 and 995 +/- 691 mg/kg x 24 h, P = 0.503), 
      but the first 12 h (AUC0-12h) was lower with evening versus morning glargine (357 
      +/- 244 vs. 593 +/- 374 mg/kg x 12 h, P = 0.004), whereas the opposite occurred for 
      the second 12 h (AUC12-24h 700 +/- 396 vs. 403 +/- 343 mg/kg x 24 h, P = 0.002). The 
      glucose infusion rate differences were totally accounted for by different rates 
      of endogenous glucose production, not utilization. Plasma insulin and C-peptide 
      levels did not differ in evening versus morning studies. Plasma glucagon levels 
      (AUC0-24h 1,533 +/- 656 vs. 1,120 +/- 344 ng/L/h, P = 0.027) and lipolysis (free 
      fatty acid AUC0-24h 7.5 +/- 1.6 vs. 8.9 +/- 1.9 mmol/L/h, P = 0.005; beta-OH-butyrate 
      AUC0-24h 6.8 +/- 4.7 vs. 17.0 +/- 11.9 mmol/L/h, P = 0.005; glycerol, P < 0.020) were 
      overall more suppressed after evening versus morning glargine administration. 
      CONCLUSIONS: The PD of insulin glargine differs depending on time of 
      administration. With morning administration insulin activity is greater in the 
      first 0-12 h, while with evening administration the activity is greater in the 
      12-24 h period following dosing. However, glargine PK and plasma C-peptide levels 
      were similar, as well as glargine PD when analyzed by 24-h clock time independent 
      of the time of administration. Thus, the results reflect the impact of circadian 
      changes in insulin sensitivity in T2DM (lower in the night-early morning vs. 
      afternoon hours) rather than glargine per se.
CI  - (c) 2015 by the American Diabetes Association. Readers may use this article as long 
      as the work is properly cited, the use is educational and not for profit, and the 
      work is not altered.
FAU - Porcellati, Francesca
AU  - Porcellati F
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
FAU - Lucidi, Paola
AU  - Lucidi P
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
FAU - Cioli, Patrizia
AU  - Cioli P
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
FAU - Candeloro, Paola
AU  - Candeloro P
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
FAU - Marinelli Andreoli, Anna
AU  - Marinelli Andreoli A
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
FAU - Marzotti, Stefania
AU  - Marzotti S
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
FAU - Ambrogi, Maura
AU  - Ambrogi M
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
FAU - Bolli, Geremia B
AU  - Bolli GB
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy 
      geremia.bolli@unipg.it.
FAU - Fanelli, Carmine G
AU  - Fanelli CG
AD  - Department of Medicine, University of Perugia Medical School, Perugia, Italy.
LA  - eng
SI  - EudraCT/2010-019368-35
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20141218
PL  - United States
TA  - Diabetes Care
JT  - Diabetes care
JID - 7805975
RN  - 0 (Blood Glucose)
RN  - 0 (C-Peptide)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin, Long-Acting)
RN  - 2ZM8CX04RZ (Insulin Glargine)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Aged
MH  - Blood Glucose/analysis
MH  - C-Peptide/blood
MH  - Circadian Rhythm
MH  - Cross-Over Studies
MH  - Diabetes Mellitus, Type 2/*drug therapy/*metabolism
MH  - Drug Administration Schedule
MH  - Fatty Acids, Nonesterified/blood
MH  - Female
MH  - Glucose/administration & dosage/pharmacokinetics
MH  - Glucose Clamp Technique
MH  - Humans
MH  - Hypoglycemic Agents/*administration & dosage/*pharmacokinetics
MH  - Injections
MH  - Insulin Glargine
MH  - Insulin Resistance
MH  - Insulin, Long-Acting/*administration & dosage/*pharmacokinetics
MH  - Male
MH  - Middle Aged
EDAT- 2014/12/20 06:00
MHDA- 2015/09/12 06:00
CRDT- 2014/12/20 06:00
PHST- 2014/12/20 06:00 [entrez]
PHST- 2014/12/20 06:00 [pubmed]
PHST- 2015/09/12 06:00 [medline]
AID - dc14-0649 [pii]
AID - 10.2337/dc14-0649 [doi]
PST - ppublish
SO  - Diabetes Care. 2015 Mar;38(3):503-12. doi: 10.2337/dc14-0649. Epub 2014 Dec 18.