Girls with obesity and polycystic ovarian syndrome will receive either glucagon like peptide-1 receptor agonist therapy or a dietary intervention for 12 weeks to decrease the metabolic syndrome, in particular to lower hepatic fat and improve insulin sensitivity.
In obese girls with polycystic ovarian syndrome, testosterone and obesity combine to create unique pathology to increase metabolic disease including fatty liver and insulin resistance, which may be mediated by altered glucagon like peptide-1 activity. The investigators will treat girls with obesity and polycystic ovarian syndrome for 4 months with a glucagon like peptide-1 receptor agonist compared to dietary intervention to primarily lower hepatic fat and secondarily improve whole body and adipose insulin sensitivity. Mechanisms of hepatic metabolism, including rates of de novo lipogenesis and relative mitochondrial flux will also be assessed.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
60
Once daily oral tablet of semaglutide for 4 months
Prescribed weight loss diet to match weight loss in Drug arm
University of Colorado Anshutz Medical Campus/Children's Hospital Colorado
Aurora, Colorado, United States
Change in Hepatic Fat Fraction
Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%. A negative value means a decrease in liver fat, and a positive value means an increase in liver fat.
Time frame: Baseline and 12 weeks
Change in Weight
Change in weight will be calculated for each group (diet and semaglutide), and both the absolute and relative weight changes between the two groups will be reported.
Time frame: Baseline and 12 weeks
Change in Rate of De Novo Lipogenesis (DNL)
Change from baseline of the rate of overnight de novo lipogenesis (DNL) will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction. A negative value means a decrease in newly synthesized lipids after the 12 week intervention, and a positive value means an increase in newly synthesized lipids after the 12 week intervention. A lower value is better.
Time frame: Baseline and 12 weeks
Change in Whole Body Insulin Sensitivity
Participants will undergo a 75 gram oral glucose tolerance test, and the change from baseline in whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model.
Time frame: Baseline and 12 weeks
Change in Adipose Insulin Sensitivity
Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids, and the nadir of free fatty acids during the oral glucose tolerance test. Percent suppression of FFAs during the OGTT was calculated as fasting FFA minus the minimal FFA value divided by fasting FFA. This was calculated for baseline and after 12-weeks of intervention. The change was calculated by subtracting the final-baseline values. A higher absolute value means there was an improvement in adipose insulin sensitivity after 12-weeks of treatment.
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Time frame: Baseline and 12 weeks