PMID- 27450071
OWN - NLM
STAT- MEDLINE
DCOM- 20171205
LR  - 20221207
IS  - 1365-2125 (Electronic)
IS  - 0306-5251 (Print)
IS  - 0306-5251 (Linking)
VI  - 82
IP  - 6
DP  - 2016 Dec
TI  - Application of the integrated glucose-insulin model for cross-study 
      characterization of T2DM patients on metformin background treatment.
PG  - 1613-1624
LID - 10.1111/bcp.13069 [doi]
AB  - AIM: The integrated glucose-insulin (IGI) model is a semi-mechanistic 
      physiological model which can describe the glucose-insulin homeostasis system 
      following various glucose challenge settings. The aim of the present work was to 
      apply the model to a large and diverse population of metformin-only-treated type 
      2 diabetes mellitus (T2DM) patients and identify patient-specific covariates. 
      METHODS: Data from four clinical studies were pooled, including glucose and 
      insulin concentration-time profiles from T2DM patients on stable treatment with 
      metformin alone following mixed-meal tolerance tests. The data were collected 
      from a wide range of patients with respect to the duration of diabetes and level 
      of glycaemic control. RESULTS: The IGI model was expanded by four 
      patient-specific covariates. The level of glycaemic control, represented by 
      baseline glycosylated haemoglobin was identified as a significant covariate for 
      steady-state glucose, insulin-dependent glucose clearance and the magnitude of 
      the incretin effect, while baseline body mass index was a significant covariate 
      for steady-state insulin levels. In addition, glucose dose was found to have an 
      impact on glucose absorption rate. The developed model was used to simulate 
      glucose and insulin profiles in different groups of T2DM patients, across a range 
      of glycaemic control, and it was found accurately to characterize their response 
      to the standard oral glucose challenge. CONCLUSIONS: The IGI model was 
      successfully applied to characterize differences between T2DM patients across a 
      wide range of glycaemic control. The addition of patient-specific covariates in 
      the IGI model might be valuable for the future development of antidiabetic 
      treatment and for the design and simulation of clinical studies.
CI  - (c) 2016 The British Pharmacological Society.
FAU - Parkinson, Joanna
AU  - Parkinson J
AD  - Cardiovascular & Metabolic Disease, Innovative Medicines and Early Development 
      Biotech Unit, AstraZeneca, Molndal, 431 83, Sweden.
FAU - Hamren, Bengt
AU  - Hamren B
AD  - Cardiovascular & Metabolic Disease, Innovative Medicines and Early Development 
      Biotech Unit, AstraZeneca, Molndal, 431 83, Sweden.
FAU - Kjellsson, Maria C
AU  - Kjellsson MC
AD  - Pharmacometrics Research Group, Department of Pharmaceutical Biosciences, Uppsala 
      University, Sweden.
FAU - Skrtic, Stanko
AU  - Skrtic S
AD  - Cardiovascular & Metabolic Disease, Innovative Medicines and Early Development 
      Biotech Unit, AstraZeneca, Molndal, 431 83, Sweden.
AD  - Department of Endocrinology, Sahlgrenska University Hospital and Institute of 
      Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160816
PL  - England
TA  - Br J Clin Pharmacol
JT  - British journal of clinical pharmacology
JID - 7503323
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Hypoglycemic Agents)
RN  - 0 (Insulin)
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Blood Glucose/*metabolism
MH  - Diabetes Mellitus, Type 2/*blood/drug therapy
MH  - Female
MH  - Glycated Hemoglobin/analysis
MH  - Humans
MH  - Hypoglycemic Agents/*therapeutic use
MH  - Insulin/*blood
MH  - Male
MH  - Metformin/*therapeutic use
MH  - *Models, Biological
MH  - Randomized Controlled Trials as Topic
PMC - PMC5099540
OTO - NOTNLM
OT  - NONMEM
OT  - glucose
OT  - glycaemic control
OT  - insulin
OT  - integrated glucose-insulin model
OT  - type 2 diabetes mellitus
EDAT- 2016/07/28 06:00
MHDA- 2017/12/06 06:00
PMCR- 2017/12/01
CRDT- 2016/07/25 06:00
PHST- 2016/02/18 00:00 [received]
PHST- 2016/07/08 00:00 [revised]
PHST- 2016/07/17 00:00 [accepted]
PHST- 2016/07/28 06:00 [pubmed]
PHST- 2017/12/06 06:00 [medline]
PHST- 2016/07/25 06:00 [entrez]
PHST- 2017/12/01 00:00 [pmc-release]
AID - BCP13069 [pii]
AID - 10.1111/bcp.13069 [doi]
PST - ppublish
SO  - Br J Clin Pharmacol. 2016 Dec;82(6):1613-1624. doi: 10.1111/bcp.13069. Epub 2016 
      Aug 16.