Adolescent polycystic ovary syndrome (PCOS), obesity and nonalcoholic fatty liver

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 554-573-Ovarian & Uterine Function I
Basic/Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-560
Sara F Michaliszyn1, SoJung F Lee1, Hala Mounir Tfayli2 and Silva A Arslanian*3
1University of Pittsburgh, Pittsburgh, PA, 2American Univ of Beirut, Beirut, Lebanon, 3Children's Hosp of Pittsburgh of, Pittsburgh, PA
Introduction: Nonalcoholic fatty liver disease (NAFLD) is a comorbidity of obesity, dysmetabolic syndrome, insulin resistance and type 2 diabetes. Adolescent females with PCOS are characterized by obesity, severe insulin resistance and heightened risk of pre diabetes and type 2 diabetes, conditions that enhance the risk of NAFLD. Therefore, we investigated in obese adolescent girls with PCOS the relationship between liver fat and in vivo insulin sensitivity, body composition, abdominal adiposity and lipid metabolism.

Methods: Thirty Tanner stage V obese adolescent girls diagnosed with PCOS were studied [age: 16.1±0.3yrs; BMI%: 97.6±0.3; free testosterone: 8.7±0.8pg/ml, (mean±SEM)]. Liver fat was evaluated with computed tomography (CT) and fatty liver index (FLI) expressed as the ratio of liver to spleen Hounsfield attenuation units (HU) (liver HU/spleen HU < 1 indicative of fatty liver). In vivo insulin-stimulated glucose disposal was measured by a 3-hr hyperinsulinemic (80mu/m2/min)-euglycemic clamp, whole-body lipolysis and fat oxidation by [2H5]glycerol and indirect calorimetry respectively, body composition by dual energy x-ray absorptiometry, abdominal adiposity by CT scan at L4-5 intervertebral space. Fasting blood was obtained for lipoprotein particle size and concentration and liver enzymes (ALT, AST).

Results: Fatty liver was present in 2 individuals (6.7%). ALT and AST were not different between those with fatty liver vs. without (ALT: 28.0±5.0 vs. 27.4±1.7, p=0.93; AST: 23.0±1.0 vs. 22.9±0.8, p=0.98). FLI was associated with age (r=-0.53, p=0.003), total (r=-0.43, p=0.03) and subcutaneous (r=-0.41, p=0.04) abdominal adipose tissue, insulin-stimulated glucose disposal (r=0.36, p=0.05), small, medium small, and very small LDL concentrations (r>=-0.43, p=0.03). There was a trend for an association between FLI and lipolysis (r=-0.32, p=0.09), and no relationship to fat oxidation. In a multiple regression analysis, age, total testosterone, race and insulin-stimulated glucose disposal explained 43% of the variance (R2=0.43, p=0.006) in FLI, with age (R2=0.28, p=0.002) and total testosterone (R2=0.11, p=0.03) being significant independent contributors.

Conclusion: These observations suggest that in obese adolescent girls with PCOS, liver fat is associated with increasing age, increasing abdominal adiposity, worsening insulin sensitivity and dyslipoproteinemia. Targeting these abnormalities early in the course of PCOS may halt future NAFLD in adulthood.

Disclosure: SAA: Advisory Group Member, Novo Nordisk, Advisory Group Member, Sanofi, Advisory Group Member, Bristol-Myers Squibb, Consultant, Gilead Science,Inc., , Boehringer Ingelheim. Nothing to Disclose: SFM, SFL, HMT

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm

Sources of Research Support: Endocrine FellowsFoundation; T32 DK063686 (S.A.); K24-HD01357 (S.A.); Richard L. Day Endowed Chair (S.A. and H.T.); M01-RR00084; and UL1 RR024153 and UL1 TR000005 CTSA