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SUN 780-806-Determinants of Insulin Resistance & Associated Metabolic Disturbances
Expo Halls ABC (Moscone Center)
Poster Board SUN-798
BACKGROUND Hyperinsulinemia is increasingly recognized as a cause as well as a consequence of obesity and diabetes1-3 and strategies to ameliorate hyperinsulinemia are widely advocated.4 Identification of hyperinsulinemia is critical to initiation of early intervention. IGFBP-1 is an acknowledged marker of hyperinsulinemia5-7with a documented role in glucose homeostasis.7,8 Hepatic IGFBP-1 is inhibited by insulin. Low serum IGFBP-1’s correlate with metabolic syndrome (MS), and cardiovascular disease,9,10 and predict impaired glucose tolerance and Type 2 diabetes (T2DM) incidence in prospective studies.5 IGFBP-1 has excellent sensitivity & specificity as a screening test for ↑AUC-insulin11 & could be used to detect and monitor treatment in normoglycemic patients, comparable to Hb A1C in the management of T2DM. Accordingly, we measured IGFBP-1 at baseline & 6 months in EMPOWIR, a double blind, placebo controlled randomized clinical trial of metformin (MF) 2000mg & MF plus rosiglitazone (RSG) in women with Syndrome W—an early manifestation of insulin resistance, defined by the triad of Weight gain (≥20 lbs after the 20´s), Waist gain, & White Coat hypertension in normoglycemic hyperinsulinemic Women.12 The study was conducted to test the hypothesis that insulin sensitizers, along with a novel carbohydrate modified diet, could reduce fasting insulin (FIn) & attenuate related risk factors.13, 14 METHODS We compared FIn, IGFBP-1, BW, HOMA, & MS measures at baseline & 6-months in 46 subjects (mean age 46.6, BMI 30.5kg/m2, Hb A1C 5.4%) meeting inclusion criteria: age 35-55; 20 lb wt gain; normal GTT & AUC-insulin>100μU/ml. Paired t-tests & multivariate models were used (SPSS 19). Participants attended 4 weekly nutrition workshops to introduce the EMPOWIR diet: a flexible food plan (40% carbohydrates-40% protein-20% fat) promoting increased intake of vegetables, low-glycemic index fruits, low-fat protein & dairy products, restriction of all free sugars, & notable postponement of 3 allowable additional carbohydrates (starches) to after 4PM. RESULTS Significant reductions in mean BW were observed in all 3 study arms (P´s=.049, .005, .017). IGFBP-1 increased in all 3 arms (11.6→15.1, 11.2→13.2, & 11.8→19.6 ng/ml), but was only significant in the MF+RSG arm: P’s=.427, .194, .005, and was independent of weight loss. FIn reduction was significant in the MF arm (12.5→8.0µU/ml, P= .011). HOMA decreased in MF & MF+RSG arms (2.5→1.6 &1.9→1.3, P´s=.054 & .013). DISCUSSION IGFBP-1 improvement is reported in studies of women with PCOS.15-17 We believe this is the first demonstration of IGFBP-1 normalization with preventive interventions in midlife women. CONCLUSIONS Significant IGFBP-1 increase was observed in the MF+RSG arm in a diverse cohort of normoglycemic, hyperinsulinemic midlife women. IGFBP-1 may be a valuable test to diagnose and monitor hyperinsulinemia and merits additional study.
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Disclosure: HRM: Principal Investigator, GlaxoSmithKline, Clinical Researcher, Eli Lilly & Company. Nothing to Disclose: RGF, FMH, NB, MF
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
Sources of Research Support:
EMPOWIR is an unsolicited, investigator-initiated study supported by Glaxo Smith Kline with additional support from a Clinical and Translational Science Award (CTSA) from the National Institutes of Health UL11RR025740 awarded to the GCRC at Einstein.