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Mathematical modeling of hepatic and adipose insulin resistance in girls with polycystic ovarian syndrome
Simens, Jacqueline
Simens, Jacqueline
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2015
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Polycystic Ovarian Syndrome (PCOS) affects 6-10% of women in the United States and is one of the leading causes of infertility. The metabolic phenotype for PCOS includes insulin resistance (IR), and IR may vary with tissue type. The goal of this project is to determine the contributions of hepatic (liver) tissue and adipose (fat) tissue to increased IR in a cohort of adolescent females. For hepatic IR, we use the Labeled Oral Minimal Model (OMM*), originally developed by Dalla Man and colleagues. This differential equations based mathematical model describes the dynamics of glucose and insulin during an oral glucose tolerance test (OGTT) with stable isotope tracers for glucose and glycerol. Parameters for OMM* are used to quantify hepatic IR. We investigate the identifiability of this system and estimate model parameters in 6 subjects. For adipose IR, we propose a novel approach to modeling glycerol dynamics during an OGTT. We investigate the identifiability of this system and develop a numerical approach for estimating model parameters in the same cohort of 6 subjects. We propose the use of model parameters and metrics involving the numerical solution to quantify adipose IR. This work contributes to an improved understanding of tissue-specific IR, which may lead to targeted therapeutics.
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