PMID- 32895980
OWN - NLM
STAT- MEDLINE
DCOM- 20211208
LR  - 20221207
IS  - 1552-4604 (Electronic)
IS  - 0091-2700 (Linking)
VI  - 61
IP  - 2
DP  - 2021 Feb
TI  - Development and Verification of a Body Weight-Directed Disease Trial Model for 
      Glucose Homeostasis.
PG  - 234-243
LID - 10.1002/jcph.1728 [doi]
AB  - Weight loss has been associated with improvement in insulin sensitivity. It is 
      consequently a cornerstone in the management of type 2 diabetes mellitus (T2DM). 
      However, the strictly quantitative relationship between weight loss, insulin 
      sensitivity, and clinically relevant glucose homeostasis biomarkers as well as 
      changes therein as T2DM progresses is not yet fully understood. Therefore, the 
      objective of our research was to establish a body weight-directed disease trial 
      model for glucose homeostasis. To that end, we conducted a model-based 
      meta-analysis using time course data of body weight loss (following lifestyle 
      change or surgical procedure) and corresponding improvement of insulin 
      sensitivity expressed as the Matsuda index. Changes in body weight were best 
      described by a sigmoidal E(max) model, whereas changes in the Matsuda index were 
      best described by a linear model with a slope of 3.49. Once developed and 
      verified, the model-based meta-analysis was linked to a disease-drug trial model 
      for T2DM previously developed by our group to characterize and predict the impact 
      of weight loss on clinically relevant glucose homeostasis biomarkers. The joint 
      model was then used to conduct clinical trial simulations, which showed that 
      weight loss can greatly improve clinically relevant glucose homeostasis 
      biomarkers in T2DM patients.
CI  - (c) 2020, The American College of Clinical Pharmacology.
FAU - Farhan, Nashid
AU  - Farhan N
AUID- ORCID: 0000-0001-8484-5526
AD  - Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, 
      University of Florida, Orlando, Florida, USA.
FAU - Gebert, Ines
AU  - Gebert I
AD  - Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, 
      University of Florida, Orlando, Florida, USA.
FAU - Xing, Yifan
AU  - Xing Y
AD  - Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, 
      University of Florida, Orlando, Florida, USA.
FAU - Wieser, Katharina
AU  - Wieser K
AD  - Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, 
      University of Florida, Orlando, Florida, USA.
FAU - Lingineni, Karthik
AU  - Lingineni K
AD  - Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, 
      University of Florida, Orlando, Florida, USA.
FAU - Ma, Xiaosu
AU  - Ma X
AD  - Global PK/PD & Pharmacometrics, Eli Lilly & Company, Lilly Corporate Center, 
      Indianapolis, Indiana, USA.
FAU - Chien, Jenny Y
AU  - Chien JY
AD  - Global PK/PD & Pharmacometrics, Eli Lilly & Company, Lilly Corporate Center, 
      Indianapolis, Indiana, USA.
FAU - Garhyan, Parag
AU  - Garhyan P
AD  - Global PK/PD & Pharmacometrics, Eli Lilly & Company, Lilly Corporate Center, 
      Indianapolis, Indiana, USA.
FAU - Schmidt, Stephan
AU  - Schmidt S
AD  - Center for Pharmacometrics and Systems Pharmacology, College of Pharmacy, 
      University of Florida, Orlando, Florida, USA.
LA  - eng
PT  - Journal Article
PT  - Meta-Analysis
DEP - 20200907
PL  - England
TA  - J Clin Pharmacol
JT  - Journal of clinical pharmacology
JID - 0366372
RN  - 0 (Biomarkers)
RN  - 0 (Blood Glucose)
RN  - 0 (Glycated Hemoglobin A)
RN  - 0 (Insulin)
SB  - IM
MH  - Biomarkers
MH  - Blood Glucose
MH  - Diabetes Mellitus, Type 2/*physiopathology
MH  - Glycated Hemoglobin
MH  - Humans
MH  - Insulin/blood
MH  - Insulin Resistance/*physiology
MH  - *Models, Biological
MH  - Weight Loss/*physiology
OTO - NOTNLM
OT  - MBMA
OT  - Matsuda index
OT  - obesity
OT  - type 2 diabetes
OT  - weight loss
EDAT- 2020/09/09 06:00
MHDA- 2021/12/15 06:00
CRDT- 2020/09/08 05:26
PHST- 2020/06/24 00:00 [received]
PHST- 2020/08/02 00:00 [accepted]
PHST- 2020/09/09 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2020/09/08 05:26 [entrez]
AID - 10.1002/jcph.1728 [doi]
PST - ppublish
SO  - J Clin Pharmacol. 2021 Feb;61(2):234-243. doi: 10.1002/jcph.1728. Epub 2020 Sep 
      7.