Masculinized Counterregulatory Hormone Responses to Hypoglycemia in Polycystic Ovary Syndrome

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: SUN 498-523-Female Reproductive Endocrinology & Case Reports
Clinical
Sunday, June 16, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board SUN-503
Priyathama Vellanki*1, Sudha K Yalamanchi2, Richard N Bergman3 and Andrea Dunaif4
1Northwestern University, Chicago, IL, 2Feinberg School of Medicine, Nor, Chicago, IL, 3Alfred Firestein Chair Diab Rsrc, West Hollywood, CA, 4Northwestern University, Feinberg School of Medicine, Chicago, IL
Premenopausal women have blunting of many counterregulatory hormone responses (CRR) to hypoglycemia compared to men, but men have blunted cortisol responses compared to women.  Postmenopausal women have CRR similar to men.  The premenopausal pattern can be partially restored by estrogen administration.  However, glucagon responses remain higher in men than in postmenopausal women.  We performed this study to test the hypothesis that women with polycystic ovary syndrome (PCOS) have masculinized CRR to hypoglycemia.

Ten PCOS and 9 reproductively-normal premenopausal control women (C) of comparable age and BMI underwent 180 min hypoglycemic clamp studies at a 60 mU/m2/min insulin dose.  Plasma glucose was clamped at ~52 mg/dL.  Endogenous glucose production (EGP) was determined in the postabsorptive state and during the last 30 min of the clamp (steady-state) using steady-state tracer kinetics.  Insulin-mediated glucose disposal (IMGD) was the sum of the glucose infusion rate and residual EGP.  Groups were compared by two-tailed t- or non-parametric tests, as appropriate (mean ± SD).

PCOS and C women reached glucose nadir at 45 and 35 min, respectively, P< 0.001.  In the postabsorptive state, glucose levels were similar but insulin levels were higher in PCOS (PCOS 26±8 vs C 16±6 µU/mL, P=0.008).  Steady-state insulin levels were higher in PCOS (PCOS 158±35 vs C 126±16 µU/ml, P=0.02).  Neither basal nor steady-state EGP differed.  IMGD was significantly decreased in PCOS (PCOS 101±37 vs C 144±46 mg/m2/min, P=0.02), despite higher insulin levels in affected women.  The change (Δ) from postabsorptive to steady-state glucagon levels was increased in PCOS (PCOS 55±35 vs C 22±25 pg/mL, P=0.04).  There was a trend towards decreased Δ steady-state cortisol levels in PCOS (P=0.07).  Postabsorptive lactate levels were higher in PCOS (PCOS 9.3±1.7 vs C 7.1±3.1 mg/dL, P=0.03) and showed an inverse correlation with IMGD (R2= 0.27, P= 0.03).  Postabsorptive and Δ steady-state growth hormone, cortisol, catecholamines, free fatty acid, glycerol and pancreatic polypeptide levels did not differ.  

CRR modulated by estrogen did not differ in PCOS and C women.  In contrast, glucagon responses were increased in PCOS, a male pattern not entirely accounted for by differences in circulating estrogen levels.  Our findings suggest that CRR are masculinized in PCOS.  Higher basal lactate levels in PCOS may reflect decreased insulin sensitivity as reported in other insulin-resistant states.

Disclosure: AD: Speaker, Bayer Schering Pharma, Advisory Group Member, Amylin Pharmaceuticals, Advisory Group Member, Bristol-Myers Squibb. Nothing to Disclose: PV, SKY, RNB

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

Sources of Research Support: NIH/NIDDK Training Grant T32 DK007169 awarded to PV