ODP424 Postprandial Adipose Insulin Resistance in Adolescent Girls with PCOS and Obesity

Abstract Background Polycystic ovary syndrome (PCOS) is common and associated with metabolic disease, in particular glucose abnormalities and insulin resistance (IR). Fat metabolism is linked with IR, manifesting as decreased suppression of lipolysis following meals, inflammation, and ectopic fat accumulation. Our previous work demonstrated adipose IR during a hyperinsulinemic-euglycemic clamp and increased hepatic fat in adolescents with PCOS. We hypothesized that postprandial fat metabolism would be altered compared to controls with obesity. Design/Methodology Data from 133 girls aged 13-21 years with obesity (BMI >90th%ile) enrolled in 1 of 4 cross-sectional metabolic studies were included in this secondary analysis. PCOS was determined per NIH diagnostic standards. Controls had regular menses and were >1-year post-menarche. Metabolic assessments were identical across studies and included fasting labs (lipid panel, inflammatory markers, androgens, insulin sensitivity indices), 4-hour oral sugar tolerance test (OSTT, 75 grams glucose, 25 grams fructose), liver fat by MRI, and body composition by DXA. Glycerol production (Ra) D5 glycerol infusion to measure lipolysis was evaluated in a subset. Metrics of glucose, insulin, glycerol, free fatty acid (FFA), and glucagon during the OSTT were calculated including AUC, fasting, nadir, and peak. Adipo IR (fasting FAA x fasting insulin) was determined. Data between controls and girls with PCOS were compared by Student's t-tests with Welch correction. Spearman's correlations were used within groups to evaluate associations. Results Participants included 110 girls with PCOS (age 16.4±1.6 years; BMI 35.9±5.8 kg/m2) and 23 without PCOS (15.9±1.6; 34.6±6.7). Per design, markers of androgen excess including total testosterone (p<0.001), free testosterone (p<0.001), degree of hirsutism (p=0.004), and severity of acne (p<0.001) were worse in girls with PCOS. Consistent with previous work, girls with PCOS had worse markers of glycemia including higher HbA1c (p<0.001), fasting glucose (p=0.027), 2-hour glucose (p=0.008), glucose AUC (p=0.033), and insulin AUC (p=0.034). They also had higher liver (p<0.001) and visceral fat (p=0.007), total (p=0.007) and LDL cholesterol (p=0.006), and triglycerides (p=0.005). Regarding adipose IR, fasting FFA (699±175 µmol/L vs. 593±163, p=0.007), FFA nadir (68±26 vs. 51±16, p=0.003), FFA AUC (114210 vs. 92518, p = 0.018), glycerol AUC (13815 vs. 8393, p<0.0001), and Adipo IR (p=0.034) were significantly higher while fasting glycerol Ra (p=0.571) did not differ. There were no differences between groups in markers of inflammation. Within the PCOS group, higher glycerol AUC correlated with higher HbA1c (p=0.001) and highly-sensitive C-reactive protein (hsCRP) (p=0.029), while increased FFA AUC correlated with increased hsCRP (p=0.043) and AST (p=0.037), but not markers of insulin resistance or dysglycemia. Conclusions Adolescents with PCOS and obesity have increased adipose IR. Future focus and treatment of adipose IR may be a promising avenue to delay onset of metabolic syndrome complications in girls with PCOS and obesity. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.