OR02-5 Metabolomic Response to an Oral Glucose Challenge in Women with a History of Gestational Diabetes Mellitus

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: OR02-Diabetes in Pregnancy
Translational
Saturday, June 15, 2013: 11:30 AM-1:00 PM
Presentation Start Time: 12:30 PM
Room 303 (Moscone Center)
Annie Yang*1, Grace Xiong1, Hang Lee1, Catherine Kim2 and Rhonda Bentley-Lewis1
1Massachusetts General Hospital, Boston, MA, 2University of Michigan, Ann Arbor, MI
Background: Metabolomics is the science of systematically examining products of biochemical pathways in order to identify biomarkers predictive of metabolic diseases, such as type 2 diabetes. Metabolomics has been used to elucidate the response to an oral glucose tolerance test (OGTT) in normoglycemic and glucose intolerant subjects; however, this response has not been examined specifically in women with a history of GDM.

Objectives: To examine the metabolite response to an OGTT, i.e. change from fasting to 2-hour post-challenge, in women with a history of GDM and to determine if insulin resistance is associated with these changes.

Methods: We analyzed metabolomic profiles of 39 non-diabetic, non-pregnant women with a history of GDM within 3 years. Women provided information on family history of type 2 diabetes, race, parity, smoking, and breastfeeding. A 75 g-oral glucose load was given and fasting and 2-hr plasma samples were collected. Gas chromatography-mass spectrometry was employed to construct metabolite profiles on 23 amino acid (AA) or AA derivatives. Stepwise regression analyses (forward variable inclusion criteria p < 0.15) and correlations (p < 0.05) were performed to examine associations between metabolites and clinical measures.

Results: The women were 35 ± 4 years old (mean ± SD) and 69% white. They had mean fasting (90 ± 10 mg/dl) and 2-hr (125 ± 38 mg/dl) glucose levels and were insulin resistant as reflected by body mass index (BMI; 28.4 ± 5.6 kg/m2), glucose:insulin ratio (G/I, 5.5 ± 2.1) and homeostatic model assessment – insulin resistance (HOMA-IR; 6.08 ± 12.9). The levels of twenty AAs increased significantly in response to the glucose load (p < 0.0001) and G/I was most significantly associated with tyrosine levels (r = -0.43, p = 0.007).  Of the clinical parameters, breastfeeding, race, and G/I were associated with several AA levels (beta coefficients, b = 8.59 ± 1.0, -23.54 ± 2.4, and -3.43 ± 0.7 respectively, p values ranging < 0.002 to < 0.05), but the most significant association was between parity and change in cystine levels (b = 1.257, p = 0.0009).

Conclusions: Among insulin-resistant women with a recent history of GDM, breastfeeding, race, and G/I were most strongly associated with metabolite profile changes following the OGTT. Parity and cystine levels had the most significant association. Confirmation of these relationships and closer examination of the specific pathways implicated in these associations are warranted.

Nothing to Disclose: AY, GX, HL, CK, RB

*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 grant DK089503 awarded to the University of Michigan to support Metabolomic Core services; NIH 1R03DK096152 and the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program awarded to RB-L.