Hepatic Steatosis is Common in Adolescents with Obesity and PCOS and Relates to De Novo Lipogenesis but not Insulin Resistance

Abstract

Objective Increased liver fat and type 2 diabetes are prevalent in women with polycystic ovarian syndrome (PCOS) and cause excess mortality, yet little is known about their development during adolescence. Our goal was to measure hepatic steatosis and related metabolic contributors in girls with obesity, with and without PCOS. Methods Nondiabetic adolescents with obesity, 41 with PCOS (PCOS; age 15.0(13.0,16.0) years, BMI 35.2±0.61 kg/m2) and 30 without PCOS (OB; age 14.5(13.0,17.0), BMI 33.2±1.8) were studied. Visceral and liver fat were assessed with MRI. Serum measures included androgens and 16 and 18 n7 fatty acids specific to de novo lipogenesis. Adipose, hepatic and peripheral insulin sensitivity (IS) were assessed with a 4-phase hyperinsulinemic-euglycemic clamp with isotope tracers. Results 49% PCOS had hepatic steatosis vs. 14% OB (p=0.02), and PCOS had higher n7 (43±4 nmol/g vs. 29±5; p=0.02). Peripheral IS was lower in PCOS (9.4(7.2,12.3) mg/lean kg/min vs. 14.5(13.1,18.05); p<0.001) as was hepatic (p=0.006) and adipose IS (p=0.005). Percent liver fat correlated with n7 (R=0.46, p=0.02) and visceral fat (R=0.42, p<0.001), not androgens or peripheral IS. Conclusions Nearly 50% of nondiabetic girls with PCOS and obesity have hepatic steatosis, which related to visceral fat and lipogenesis, but not to IS or androgens.

Using simple clinical measures to predict insulin resistance or hyperglycemia in girls with polycystic ovarian syndrome

“…Forty‐eight participants were enrolled (28 PCOS and 20 control) from the resistance to insulin in Type 1 and Type 2 diabetes (RESISTANT) study and androgens and insulin resistance study (AIRS) cohorts with all studies performed between 2006 and 2014 . Inclusion criteria included: female sex, age 11 to 19 years, and sedentary status (<3 hours of activity per week; validated with both a 3‐day activity recall and 7‐day accelerometer use).…”

“…Forty-eight participants were enrolled (28 PCOS and 20 control) from the resistance to insulin in Type 1 and Type 2 diabetes (RESISTANT) study and androgens and insulin resistance study (AIRS) cohorts with all studies performed between 2006 and 2014. 3,21,32 On a separate morning, the participants also underwent a fasting 2-hour OGTT using a dose of 1.75 mg/kg up to a maximum of 75 mg.…”

“…Polycystic ovarian syndrome (PCOS) is a common endocrine disorder, affecting around 12% of reproductive‐aged women . Patients with PCOS can have profound insulin resistance (IR) and have an increased risk of developing metabolic aberrations, such as type 2 diabetes (T2D), non‐alcoholic fatty liver disease and cardiovascular disease, all of which start in adolescence . The Joint 2017 Pediatric Endocrine Society and North American Society for Adolescent and Pediatric Gynecology Guidelines for PCOS diagnosis and management in adolescents recommend that the presence of IR prompt further co‐morbidity testing and treatment with metformin .…”

“…risk of developing metabolic aberrations, such as type 2 diabetes (T2D), non-alcoholic fatty liver disease and cardiovascular disease, all of which start in adolescence. 1,3,4 The Joint 2017 Pediatric Endocrine Society and North American Society for Adolescent and Pediatric Gynecology Guidelines for PCOS diagnosis and management in adolescents recommend that the presence of IR prompt further comorbidity testing and treatment with metformin. 5 The 2013 Endocrine Society guidelines suggest the use of metformin as a second-line therapy in PCOS youth with hyperglycemia, defined as impaired glucose tolerance (IGT) or T2D.…”

MANAGEMENT OF ENDOCRINE DISEASE: Polycystic ovary syndrome and nonalcoholic fatty liver disease

“…Similarly, 49% of obese, non-diabetic PCOS adolescents, in comparison to 14% of obese adolescents without PCOS, had hepatic steatosis. Moreover, these authors showed that hepatic steatosis was related to the visceral fat content and lipogenesis, but not to the indices of insulin sensitivity or androgen levels (124). On the other hand, postmenopausal women without history of PCOS had similar prevalence of NAFLD as premenopausal PCOS women, and both groups had more prevalent NAFLD than premenopausal women without PCOS, which suggests possible protective effects of estrogens for the development of NAFLD in women (125).…”