Effect of Food Order on Ghrelin Suppression

e76 Diabetes Care Volume 41, May 2018

Effect of Food Order on Ghrelin Alpana P. Shukla,1 Elizabeth Mauer,2 Leon I. Igel,1 Wanda Truong,1 Suppression Anthony Casper,1 Rekha B. Kumar,1 1 Diabetes Care 2018;41:e76–e77 | https://doi.org/10.2337/dc17-2244 Katherine H. Saunders, and Louis J. Aronne1

Data suggest that the temporal sequence scores, were similar in the three meal con- were similar in the three meal conditions. of carbohydrate ingestion during a meal ditions. At 180 min, ghrelin levels remained There was an inverse correlation between has a significant impact on postprandial suppressed following the carbohydrate-last percent change in ghrelin and percent glucose (1–3), insulin, and glucagon-like meal order, while the carbohydrate-first change in glucose from baseline when as- peptide 1 (GLP-1) excursions (4) in type 2 meal led to a rebound in ghrelin to prepran- sessing all participants in the three meal diabetes, while the effects on ghrelin sup- dial levels (percent ghrelin change from conditions at the evaluated time points pression and satiety have not been reported. baseline to 180 min 211.45 6 3.86% vs. (r 520.204; P , 0.001). We did not The study design and methods have 4.13 6 4.38%; P 5 0.003) (Fig. 1). Decre- observe a significant effect of food order previously been described in detail (4). mental areas under the curve for 0–180 min on subjective VAS appetite measures. Briefly, using a crossover design, 16 subjects with overweight/obesity and metformin-treated type 2 diabetes were assigned to consume the same meal on 3daysinrandomorder:

c Carbohydrate-first meal: carbohydrate (bread and orange juice), followed 10 min later by protein (chicken) and vegetables c Carbohydrate-last meal: protein and vegetables, followed 10 min later by carbohydrate c Sandwich: all meal components to- gether, each half consumed over 10 min witha10-minintervalinbetween

Blood was sampled for glucose, insulin,

OBSERVATIONS active GLP-1, and total ghrelin measure- – ments at baseline (just before meal in- gestion) and at 30-min intervals up to 180 min. Participants rated their hunger e-LETTERS and fullness levels using a visual analog Figure 1—Ghrelin percent change from baseline following carbohydrate-first (carbs first), carbohydrate- scale (VAS) at the same time points. last (carbs last), and sandwich meal orders. Values are mean 6 SEM, n 5 16. UStatistically signif- Baseline glucose, insulin, GLP-1, and ghrelin icant difference (P 5 0.003, linear mixed-effects model) between carbs first and carbs last at concentrations,aswellashungerandsatiety 180 min.

1Comprehensive Weight Control Center, Division of Endocrinology, Diabetes and Metabolism, Weill Cornell Medicine, New York, NY 2Department of Healthcare Policy and Research, Weill Cornell Medicine, New York, NY Corresponding author: Alpana P. Shukla, [email protected]. Received 25 October 2017 and accepted 6 February 2018. © 2018 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license. care.diabetesjournals.org Shukla and Associates e77

We have previously demonstrated that composition, and more objective meas- and edited the manuscript. A.P.S. and L.J.A. are the carbohydrate-last meal pattern re- ures of satiety is needed. the guarantors of this work and, as such, had full duces postprandial glucose excursions In conclusion, to our knowledge, this is access to all the data in the study and take responsibilityforthe integrityof the dataandthe compared with other meal patterns. Con- the first study to demonstrate that ma- accuracy of the data analysis. trolling for carbohydrate amount, this nipulation of macronutrient order can im- Prior Presentation. Parts of this work were meal pattern stimulates lower insulin pact gut hormone excursions. Its clinical presented as a late-breaking abstract at the ’ fi implications for satiety and weight man- Obesity Society s Annual Scienti cMeeting, and higher GLP-1 response compared Obesity Week, Washington, DC, 29 October–2 with the carbohydrate-first pattern (4). agement require further study. November 2017. Taken together with our new findings on ghrelin suppression, this suggests References 1. Imai S, Fukui M, Kajiyama S. Effect of eating that macronutrient order during a Acknowledgments. The authors acknowledge vegetables before carbohydrates on glucose ex- meal modifies the pattern of postprandial the support and contribution of Samir H. Touhamy cursions in patients with type 2 diabetes. J Clin insulin and gut hormone secretion that and Jeselin Andono (Institute of Human Nutrition, Biochem Nutr 2014;54:7–11 could potentially impact satiety and Columbia University, New York, NY) toward subject 2. Shukla AP, Iliescu RG, Thomas CE, Aronne LJ. fi weight regulation. However, similar to recruitment and conduct of study procedures, Dr. Food order has a signi cant impact on postpran- David S. Ludwig (BostonChildren’sHospital,Boston, dial glucose and insulin levels. Diabetes Care observations in previous studies that MA) for study design, and Dr. Ana Emiliano (Rocke- 2015;38:e98–e99 have investigated gut hormone excur- feller University, New York, NY) for her critical 3. TricoD,FiliceE,Tri` firo` S, Natali A. Manipulating sions to isocaloric meal interventions review of the manuscript. The study was partially the sequence of food ingestion improves glycemic (5,6), these disparate hormonal re- supported by grant UL1 TR000457-06 to the Clin- control in type 2 diabetic patients under free- ical and Translational Science Center at Weill living conditions. Nutr Diabetes 2016;6:e226 sponses did not translate into any signif- Cornell Medicine. 4. Shukla AP, Andono J, Touhamy SH, et al. icant differences in hunger/satiety scores Funding. Funding for this study was provided by Carbohydrate-last meal pattern lowers postprandial reported by participants in the three meal the Louis and Rachel Rudin Foundation and the glucose and insulin excursions in type 2 diabetes. conditions. This result may reflect both Diane and Darryl Mallah Family Foundation. BMJ Open Diabetes Res Care 2017;5:e000440 the subjective nature of the VAS tool Duality of Interest. L.J.A. reports receiving roy- 5. Foster-Schubert KE, Overduin J, Prudom CE, alties for books on nutrition and obesity. No other et al. Acyl and total ghrelin are suppressed and the complexity of appetite regula- potential conflicts of interest relevant to this arti- strongly by ingested proteins, weakly by lipids, tion; ghrelin is the only known orexigenic cle were reported. and biphasically by carbohydrates. J Clin Endocri- peptide, whereas GLP-1 is one of several Author Contributions. A.P.S. and L.J.A. con- nol Metab 2008;93:1971–1979 anorexigenic signaling gut hormones. Fur- ceived and designed the study. A.P.S. drafted the 6. Bowen J, Noakes M, Trenerry C, Clifton PM. manuscript. A.P.S., W.T., and A.C. conducted the Energy intake, ghrelin, and cholecystokinin after therstudywithanextendedobservation study procedures and acquired the data. E.M. different carbohydrate and protein preloads in period, assessment of other gut hormones analyzed the data. A.P.S., L.I.I., R.B.K., K.H.S., and overweight men. J Clin Endocrinol Metab 2006; using meals with different macronutrient L.J.A. interpreted the data. All authors reviewed 91:1477–1483