Abstracts - Orals, Featured Poster Presentations, and Posters
FP09-Obesity: Physiologic Responses to Energy Balance Disruption
Bench to Bedside
Presentation Start Time: 11:15 AM
Room 307 (Moscone Center)
Poster Board SAT-660
Ghrelin (Ghr) is a potent orexigen with a well defined role in meal initiation, food intake and long-term body weight (BW) regulation.1 Ghr has been implicated in hyperphagia of Prader Willi Syndrome,2 3appetite dysregulation from sleep deprivation,4 and weight loss associated with bariatric surgery.5 Ghr levels typically rise with diet-induced weight loss5, 6 and are believed to contribute to weight regain as part of a complex adaptive process.7 Strategies to diminish this rise might avert weight regain. EMPOWIR, is a double blind, placebo controlled, randomized trial of a novel carbohydrate modified diet (CMD) alone, and in combination with 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, and White Coat hypertension in normoglycemic hyperinsulinemic Women.8 The study was conducted to test the hypothesis that insulin sensitizers along with CMD could reduce fasting insulin and BW. CMD is 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 as previously reported.9, 10 The selected macronutrient composition reflects research on ad libitum intake11 and protein induced ghrelin suppression.12, 13 METHODS We assessed total Ghr (RIA, Millipore, Boston) and BW at baseline & 6-months at a single study site (n=22; 32% white, 41% black, 18% Hispanic, 9% other) mean age 46.2, BMI 31.1kg/m2; metabolic study criteria: normal GTT & AUC-insulin>100μU/ml. Paired t-tests & multivariate models were used (SPSS 19). Participants attended 4 weekly nutrition workshops prior to randomization. RESULTS Significant BW reductions were observed in all groups (P´s=.049, .005, .017). Mean basal Ghr declined significantly (1392±113.8 →1149±75 pg/ml, P= .001) in all groups (1240→1084 P=.046, 1052→878, P=.057 and 1984→1529 P=.031pg/ml); with Ghr reductions in 20 of 22 subjects. DISCUSSIONS Our data are consistent with most,14-19 but not all20-22 comparable intervention studies. CONCLUSION Significant Ghr decline was noted after weight loss with CMD alone, and in combination with insulin sensitizers in diverse midlife women. These findings contrast with the results of most dietary studies and merit additional study.
1. Cummings DE, Shannon MH. Roles for ghrelin in the regulation of appetite and body weight. Arch Surg 2003;138(4):389-396. 2. Cummings DE, Clement K, Purnell JQ et al. Elevated plasma ghrelin levels in Prader Willi syndrome. Nat Med 2002;8(7):643-644. 3. Haqq AM, Farooqi IS, O'Rahilly S et al. Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. J Clin Endocrinol Metab 2003;88(1):174-178. 4. Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 2004;1(3):e62. 5. Cummings DE, Weigle DS, Frayo RS et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med 2002;346(21):1623-1630. 6. Hansen TK, Dall R, Hosoda H et al. Weight loss increases circulating levels of ghrelin in human obesity. Clin Endocrinol (Oxf) 2002;56(2):203-206. 7. Cummings DE, Foster-Schubert KE, Overduin J. Ghrelin and energy balance: focus on current controversies. Curr Drug Targets 2005;6(2):153-169. 8. Mogul HR, Weinstein BI, Mogul DB et al. Syndrome W: a new model of hyperinsulinemia, hypertension and midlife weight gain in healthy women with normal glucose tolerance. Heart Dis 2002;4(2):78-85. 9. Mogul HR, Peterson SJ, Weinstein BI, Zhang S, Southren AL. Metformin and carbohydrate-modified diet: a novel obesity treatment protocol: preliminary findings from a case series of nondiabetic women with midlife weight gain and hyperinsulinemia. Heart Dis 2001;3(5):285-292. 10. Mogul HR, Peterson SJ, Weinstein BI, Li J, Southren AL. Long-term (2-4 year) weight reduction with metformin plus carbohydrate-modified diet in euglycemic, hyperinsulinemic, midlife women (Syndrome W). Heart Dis 2003;5(6):384-392. 11. Ludwig DS, Majzoub JA, Al-Zahrani A, Dallal GE, Blanco I, Roberts SB. High glycemic index foods, overeating, and obesity. Pediatrics 1999;103(3):E26. 12. Lomenick JP, Melguizo MS, Mitchell SL, Summar ML, Anderson JW. Effects of meals high in carbohydrate, protein, and fat on ghrelin and peptide YY secretion in prepubertal children. J Clin Endocrinol Metab 2009;94(11):4463-4471. 13. Foster-Schubert KE, Overduin J, Prudom CE et al. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab 2008;93(5):1971-1979. 14. English PJ, Ashcroft A, Patterson M et al. Metformin prolongs the postprandial fall in plasma ghrelin concentrations in type 2 diabetes. Diabetes Metab Res Rev 2007;23(4):299-303. 15. Kusaka I, Nagasaka S, Horie H, Ishibashi S. Metformin, but not pioglitazone, decreases postchallenge plasma ghrelin levels in type 2 diabetic patients: a possible role in weight stability? Diabetes Obes Metab 2008;10(11):1039-1046. 16. Kiyici S, Ersoy C, Oz GO et al. Total and acylated ghrelin levels in type 2 diabetic patients: similar levels observed after treatment with metformin, pioglitazone or diet therapy. Exp Clin Endocrinol Diabetes 2009;117(8):386-390. 17. Martin CK, Gupta AK, Smith SR, Greenway FL, Han H, Bray GA. Effect of pioglitazone on energy intake and ghrelin in diabetic patients. Diabetes Care 2010;33(4):742-744. 18. Rudovich N, Mohlig M, Otto B et al. Effect of meglitinides on postprandial ghrelin secretion pattern in type 2 diabetes mellitus. Diabetes Technol Ther 2010;12(1):57-64. 19. Taslimi S, Esteghamati A, Rashidi A, Tavakkoli HM, Nakhjavani M, Kebriaee-Zadeh A. Treatment with pioglitazone is associated with decreased preprandial ghrelin levels: A randomized clinical trial. Peptides 2012. 20. Pagotto U, Gambineri A, Vicennati V, Heiman ML, Tschop M, Pasquali R. Plasma ghrelin, obesity, and the polycystic ovary syndrome: correlation with insulin resistance and androgen levels. J Clin Endocrinol Metab 2002;87(12):5625-5629. 21. Schofl C, Horn R, Schill T, Schlosser HW, Muller MJ, Brabant G. Circulating ghrelin levels in patients with polycystic ovary syndrome. J Clin Endocrinol Metab 2002;87(10):4607-4610. 22. Doogue MP, Begg EJ, Moore MP, Lunt H, Pemberton CJ, Zhang M. Metformin increases plasma ghrelin in Type 2 diabetes. Br J Clin Pharmacol 2009;68(6):875-882.
Disclosure: HRM: Principal Investigator, GlaxoSmithKline, Clinical Researcher, Eli Lilly & Company. Nothing to Disclose: RGF, GC, 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.