FP19-2 PERSISTENT DEFECTS IN PANCREATIC β-CELL FUNCTION IN EARLY PUBERTAL FEMALE RELATIVES OF WOMEN WITH POLYCYSTIC OVARY SYNDROME IN A THREE YEAR LONGITUDINAL STUDY

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: FP19-Female Reproductive Endocrinology
Basic/Clinical
Sunday, June 16, 2013: 10:45 AM-11:15 AM
Presentation Start Time: 10:50 AM
Room 102 (Moscone Center)

Poster Board SUN-501
Laura Christine Torchen*1, Naomi R Fogel1, Wendy Brickman1, Rodis Paparodis2 and Andrea Dunaif3
1Feinberg School of Medicine, Northwestern University, Chicago, IL, 2University of Wisconsin School of Medicine and Public Health, Madison, WI, 3Northwestern University, Feinberg School of Medicine, Chicago, IL
First-degree female relatives (FDRs) of women with polycystic ovary syndrome (PCOS) are at substantially increased risk for PCOS. Although PCOS cannot be diagnosed until after menarche, reproductive and metabolic abnormalities are present earlier in FDRs.  We reported β-cell dysfunction and hyperandrogenemia in early pubertal FDR compared to control girls. This cohort was followed prospectively to investigate the evolution of these abnormalities.  

Twelve FDR and 10 control (CON) girls aged 8-12 y, breast Tanner Stage (bTS) I-III, BMI >85th- ≤98th percentile were studied at Year 1 (mean age 10.0 y, mean bTS II); 7 FDR and 8 CON returned at Year 2 (mean age 10.9 y, mean bTS III), and 6 FDR and 8 CON returned at Year 3 (mean age 11.5 y, mean bTS IV). Insulin sensitivity and secretion were assessed by frequently sampled intravenous glucose tolerance testing.

The groups were of similar age, bTS and BMI Z-score for the duration of the study.  Three FDRs had dysglycemia at baseline. All CON had normal glucose tolerance at baseline by design. Two dysglycemic FDRs did not participate in the prospective study. Impaired glucose tolerance normalized by Year 2 in one FDR. The significant decrease in disposition index (DI), the product of acute insulin response to glucose (AIRg) and insulin sensitivity index (SI), persisted over 3 years in FDR compared to CON girls (P=0.003). SI and visceral adipose tissue volume did not differ significantly between the groups. Data on age at menarche was available for 9 FDRs. Eight of 9 FDRs were postmenarchal, with a mean age at menarche of 12.1 years, similar to the average age of menarche in the US of 12.0 years according to 2007-2008 NHANES data. The significant increases in testosterone (T) levels in FDR compared to CON girls at Year 1 did not persist in Years 2 and 3 as CON T levels increased. Sex hormone binding globulin, DHEAS and androstenedione levels did not differ between the groups at any time point.

In conclusion, DI, the most powerful predictor of type 2 diabetes risk, remains significantly decreased in FDR girls during puberty. These findings suggest that there are persistent defects in β-cell function in PCOS FDR girls. Further, DI is decreased without significant decreases in SI suggesting that β-cell dysfunction precedes insulin resistance. Accordingly, therapies targeting insulin secretion rather than insulin action may be more successful for diabetes prevention in girls at risk for PCOS.

Disclosure: AD: Speaker, Bayer Schering Pharma, Advisory Group Member, Amylin Pharmaceuticals, Advisory Group Member, Bristol-Myers Squibb. Nothing to Disclose: LCT, NRF, WB, RP

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