PMID- 31499737
OWN - NLM
STAT- MEDLINE
DCOM- 20200922
LR  - 20200922
IS  - 1551-0018 (Electronic)
IS  - 1547-1063 (Print)
IS  - 1547-1063 (Linking)
VI  - 16
IP  - 5
DP  - 2019 Jun 20
TI  - Modeling the dynamics of glucose, insulin, and free fatty acids with time delay: 
      The impact of bariatric surgery on type 2 diabetes mellitus.
PG  - 5765-5787
LID - 10.3934/mbe.2019288 [doi]
AB  - The role of free fatty acids (FFA) on Type 2 diabetes mellitus (T2DM) progression 
      has been studied extensively with prior studies suggesting that individuals with 
      shared familial genetic predisposition to metabolic-related diseases may be 
      vulnerable to dysfunctional plasma FFA regulation. A harmful cycle arises when 
      FFA are not properly regulated by insulin contributing to the development of 
      insulin resistance, a key indicator for T2DM, since prolonged insulin resistance 
      may lead to hyperglycemia. We introduce a hypothesis-driven dynamical model and 
      use it to evaluate the role of FFA on insulin resistance progression that is 
      mathematically constructed within the context of individuals that have genetic 
      predisposition to dysfunctional plasma FFA. The dynamics of the nonlinear 
      interactions that involve glucose, insulin, and FFA are modeled by incorporating 
      a fixed-time delay with the corresponding delay-differential equations being 
      studied numerically. The results of computational studies, that is, extensive 
      simulations, are compared to the known minimal ordinary differential equations 
      model. Parameter estimation and model validation are carried out using clinical 
      data of patients who underwent bariatric surgery. These estimates provide a 
      quantitative measure that is used to evaluate the regulation of lipolysis by 
      insulin action measured by insulin sensitivity, within a metabolically 
      heterogeneous population (non-diabetic to diabetic). Results show that key 
      metabolic factors improve after surgery, such as the effect of insulin inhibition 
      of FFA on insulin and glucose regulation, results that do match prior clinical 
      studies. These findings indicate that the reduction in weight or body mass due to 
      surgery improve insulin action for the regulation of glucose, FFA, and insulin 
      levels. This reinforces what we know, namely, that insulin action is essential 
      for regulating FFA and glucose levels and is a robust effect that can be observed 
      not only in the long-term, but also in the short-term; thereby preventing the 
      manifestation of T2DM.
FAU - Murillo, Anarina L
AU  - Murillo AL
AD  - Simon A Levin Mathematical, Computational and Modeling Sciences Center, Arizona 
      State University, Tempe, AZ, USA.
AD  - Department of Biostatistics, School of Public Health, University of Alabama at 
      Birmingham, 1720 2nd Ave S, Birmingham, Alabama, USA.
FAU - Li, Jia Xu
AU  - Li JX
AD  - Simon A Levin Mathematical, Computational and Modeling Sciences Center, Arizona 
      State University, Tempe, AZ, USA.
AD  - Department of Mathematics, University of Louisville, 328 Natural Sciences 
      Building, Louisville, Kentucky, USA.
FAU - Castillo-Chavez, Carlos
AU  - Castillo-Chavez C
AD  - Simon A Levin Mathematical, Computational and Modeling Sciences Center, Arizona 
      State University, Tempe, AZ, USA.
AD  - Division of Applied Mathematics, Brown University, 182 George Street, Providence, 
      Rhode Island, USA.
LA  - eng
GR  - P30 DK079626/DK/NIDDK NIH HHS/United States
GR  - T32 HL072757/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Math Biosci Eng
JT  - Mathematical biosciences and engineering : MBE
JID - 101197794
RN  - 0 (Blood Glucose)
RN  - 0 (Fatty Acids, Nonesterified)
RN  - 0 (Insulin)
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - *Bariatric Surgery
MH  - Blood Glucose/*metabolism
MH  - Body Mass Index
MH  - Body Weight
MH  - Diabetes Mellitus, Type 2/blood/complications/*surgery
MH  - Disease Progression
MH  - Fatty Acids, Nonesterified/*blood
MH  - Female
MH  - Follow-Up Studies
MH  - Genetic Predisposition to Disease
MH  - Glucose Tolerance Test
MH  - Humans
MH  - Insulin/*blood
MH  - Insulin Resistance
MH  - Male
MH  - Middle Aged
MH  - Models, Theoretical
MH  - Obesity, Morbid/blood/complications/*surgery
MH  - Time-to-Treatment
PMC - PMC6765335
MID - NIHMS1051671
OTO - NOTNLM
OT  - free fatty acids
OT  - mathematical model
OT  - type 2 diabetes
COIS- Conflict of interest No potential conflict of interest was reported by the 
      authors.
EDAT- 2019/09/11 06:00
MHDA- 2020/09/23 06:00
PMCR- 2019/09/28
CRDT- 2019/09/11 06:00
PHST- 2019/09/11 06:00 [entrez]
PHST- 2019/09/11 06:00 [pubmed]
PHST- 2020/09/23 06:00 [medline]
PHST- 2019/09/28 00:00 [pmc-release]
AID - 10.3934/mbe.2019288 [doi]
PST - ppublish
SO  - Math Biosci Eng. 2019 Jun 20;16(5):5765-5787. doi: 10.3934/mbe.2019288.