Journal Article
. 2013 Jan; 36(7):1913-8.
doi: 10.2337/dc12-2294.

Effects of a D-xylose preload with or without sitagliptin on gastric emptying, glucagon-like peptide-1, and postprandial glycemia in type 2 diabetes

Tongzhi Wu 1 Michelle J Bound  Beiyi R Zhao  Scott D Standfield  Max Bellon  Karen L Jones  Michael Horowitz  Christopher K Rayner  
  • PMID: 23359361
  •     40 References
  •     19 citations


Objective: Macronutrient "preloads" can reduce postprandial glycemia by slowing gastric emptying and stimulating glucagon-like peptide-1 (GLP-1) secretion. An ideal preload would entail minimal additional energy intake and might be optimized by concurrent inhibition of dipeptidyl peptidase-4 (DPP-4). We evaluated the effects of a low-energy D-xylose preload, with or without sitagliptin, on gastric emptying, plasma intact GLP-1 concentrations, and postprandial glycemia in type 2 diabetes.

Research Design And Methods: Twelve type 2 diabetic patients were studied on four occasions each. After 100 mg sitagliptin (S) or placebo (P) and an overnight fast, patients consumed a preload drink containing either 50 g D-xylose (X) or 80 mg sucralose (control [C]), followed after 40 min by a mashed potato meal labeled with (13)C-octanoate. Blood was sampled at intervals. Gastric emptying was determined.

Results: Both peak blood glucose and the amplitude of glycemic excursion were lower after PX and SC than PC (P < 0.01 for each) and were lowest after SX (P < 0.05 for each), while overall blood glucose was lower after SX than PC (P < 0.05). The postprandial insulin-to-glucose ratio was attenuated (P < 0.05) and gastric emptying was slower (P < 0.01) after D-xylose, without any effect of sitagliptin. Plasma GLP-1 concentrations were higher after D-xylose than control only before the meal (P < 0.05) but were sustained postprandially when combined with sitagliptin (P < 0.05).

Conclusions: In type 2 diabetes, acute administration of a D-xylose preload reduces postprandial glycemia and enhances the effect of a DPP-4 inhibitor.

Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men.
Amelia N Pilichiewicz, Reawika Chaikomin, +6 authors, Christine Feinle-Bisset.
Am J Physiol Endocrinol Metab, 2007 Jul 05; 293(3). PMID: 17609258
Management of hyperglycaemia in type 2 diabetes: a patient-centered approach. Position statement of the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).
S E Inzucchi, R M Bergenstal, +7 authors, D R Matthews.
Diabetologia, 2012 Apr 25; 55(6). PMID: 22526604
Highly Cited.
Utility of casual postprandial glucose levels in type 2 diabetes management.
Imad M El-Kebbi, David C Ziemer, +3 authors, Lawrence S Phillips.
Diabetes Care, 2004 Jan 30; 27(2). PMID: 14747210
Comparative effects of glucose and xylose on blood pressure, gastric emptying and incretin hormones in healthy older subjects.
Lora Vanis, Trygve Hausken, +5 authors, Karen L Jones.
Br J Nutr, 2011 Feb 08; 105(11). PMID: 21294929
Measurement of gastric emptying rate of solids by means of a carbon-labeled octanoic acid breath test.
Y F Ghoos, B D Maes, +4 authors, G Vantrappen.
Gastroenterology, 1993 Jun 01; 104(6). PMID: 8500721
Highly Cited.
A glucose transporter can mediate ribose uptake: definition of residues that confer substrate specificity in a sugar transporter.
Christina M Naula, Flora J Logan, +3 authors, Richard J Burchmore.
J Biol Chem, 2010 Jul 06; 285(39). PMID: 20601430    Free PMC article.
Mechanisms for the antihyperglycemic effect of sitagliptin in patients with type 2 diabetes.
Elza Muscelli, Arturo Casolaro, +7 authors, Ele Ferrannini.
J Clin Endocrinol Metab, 2012 Jun 12; 97(8). PMID: 22685234
DPP-4 inhibitors.
Bo Ahrén.
Best Pract Res Clin Endocrinol Metab, 2007 Dec 07; 21(4). PMID: 18054733
Initially more rapid small intestinal glucose delivery increases plasma insulin, GIP, and GLP-1 but does not improve overall glycemia in healthy subjects.
Reawika Chaikomin, Selena Doran, +4 authors, Michael Horowitz.
Am J Physiol Endocrinol Metab, 2005 May 12; 289(3). PMID: 15886226
Upper gastrointestinal function and glycemic control in diabetes mellitus.
Reawika Chaikomin, Christopher K Rayner, Karen-L Jones, Michael Horowitz.
World J Gastroenterol, 2006 Sep 29; 12(35). PMID: 17007012    Free PMC article.
Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects.
M Horowitz, M A Edelbroek, J M Wishart, J W Straathof.
Diabetologia, 1993 Sep 01; 36(9). PMID: 8405758
Highly Cited.
Dietary effects on incretin hormone secretion.
Tongzhi Wu, Christopher K Rayner, Karen Jones, Michael Horowitz.
Vitam Horm, 2010 Nov 26; 84. PMID: 21094897
Effects of fat on gastric emptying of and the glycemic, insulin, and incretin responses to a carbohydrate meal in type 2 diabetes.
Diana Gentilcore, Reawika Chaikomin, +5 authors, Michael Horowitz.
J Clin Endocrinol Metab, 2006 Mar 16; 91(6). PMID: 16537685
Inhibition of dipeptidyl peptidase-4 by vildagliptin during glucagon-like Peptide 1 infusion increases liver glucose uptake in the conscious dog.
Dale S Edgerton, Kathryn M S Johnson, +5 authors, Alan D Cherrington.
Diabetes, 2008 Oct 09; 58(1). PMID: 18840785    Free PMC article.
Effect of the artificial sweetener, sucralose, on gastric emptying and incretin hormone release in healthy subjects.
Jing Ma, Max Bellon, +5 authors, Christopher K Rayner.
Am J Physiol Gastrointest Liver Physiol, 2009 Feb 18; 296(4). PMID: 19221011    Free PMC article.
Effects of a protein preload on gastric emptying, glycemia, and gut hormones after a carbohydrate meal in diet-controlled type 2 diabetes.
Jing Ma, Julie E Stevens, +6 authors, Christopher K Rayner.
Diabetes Care, 2009 Jun 23; 32(9). PMID: 19542012    Free PMC article.
Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus.
M A Nauck, M M Heimesaat, +3 authors, W Creutzfeldt.
J Clin Invest, 1993 Jan 01; 91(1). PMID: 8423228    Free PMC article.
Highly Cited.
Role of incretin hormones in the regulation of insulin secretion in diabetic and nondiabetic humans.
Jens Juul Holst, Jesper Gromada.
Am J Physiol Endocrinol Metab, 2004 Jul 24; 287(2). PMID: 15271645
Highly Cited. Review.
Intestinal absorption of D-xylose in man.
N Engl J Med, 1962 Aug 09; 267. PMID: 13894031
Effects of different sweet preloads on incretin hormone secretion, gastric emptying, and postprandial glycemia in healthy humans.
Tongzhi Wu, Beiyi R Zhao, +7 authors, Christopher K Rayner.
Am J Clin Nutr, 2011 Dec 14; 95(1). PMID: 22158727
Gastric emptying in early noninsulin-dependent diabetes mellitus.
K L Jones, M Horowitz, +3 authors, L Green.
J Nucl Med, 1996 Oct 01; 37(10). PMID: 8862300
The gut hormones PYY 3-36 and GLP-1 7-36 amide reduce food intake and modulate brain activity in appetite centers in humans.
Akila De Silva, Victoria Salem, +8 authors, Waljit S Dhillo.
Cell Metab, 2011 Oct 18; 14(5). PMID: 22000927    Free PMC article.
Effect of the artificial sweetener, sucralose, on small intestinal glucose absorption in healthy human subjects.
Jing Ma, Jessica Chang, +4 authors, Christopher K Rayner.
Br J Nutr, 2010 Apr 28; 104(6). PMID: 20420761
Suppression of glucose production by GLP-1 independent of islet hormones: a novel extrapancreatic effect.
Ronald L Prigeon, Shaista Quddusi, Breay Paty, David A D'Alessio.
Am J Physiol Endocrinol Metab, 2003 May 30; 285(4). PMID: 12773303
Simultaneous 13C/14C dual isotope breath test measurement of gastric emptying of solid and liquid in normal subjects and patients: comparison with scintigraphy.
Chong G Chew, Francis D L Bartholomeusz, Max Bellon, Barry E Chatterton.
Nucl Med Rev Cent East Eur, 2003 Nov 06; 6(1). PMID: 14600930
Actions of glucose and potassium chloride on osmoreceptors slowing gastric emptying.
G R Barker, G M Cochrane, +2 authors, S K Roberts.
J Physiol, 1974 Feb 01; 237(1). PMID: 4822585    Free PMC article.
Effect of age on fructose malabsorption in children presenting with gastrointestinal symptoms.
Hilary F Jones, Esther Burt, +3 authors, Ross N Butler.
J Pediatr Gastroenterol Nutr, 2011 Apr 20; 52(5). PMID: 21502829
The incretin system: glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes.
Daniel J Drucker, Michael A Nauck.
Lancet, 2006 Nov 14; 368(9548). PMID: 17098089
Highly Cited. Review.
The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study.
J E Stevens, M Horowitz, +3 authors, K L Jones.
Aliment Pharmacol Ther, 2012 Jun 29; 36(4). PMID: 22738299
Physiological hyperglycemia slows gastric emptying in normal subjects and patients with insulin-dependent diabetes mellitus.
E Schvarcz, M Palmér, +3 authors, C Berne.
Gastroenterology, 1997 Jul 01; 113(1). PMID: 9207262
Dipeptidyl peptidase-4 inhibitors administered in combination with metformin result in an additive increase in the plasma concentration of active GLP-1.
E M Migoya, R Bergeron, +19 authors, R SinhaRoy.
Clin Pharmacol Ther, 2010 Nov 05; 88(6). PMID: 21048706
Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man.
A-B Witte, P Grybäck, +4 authors, P T Schmidt.
Regul Pept, 2009 Aug 05; 158(1-3). PMID: 19651163
Endogenous glucagon-like peptide-1 slows gastric emptying in healthy subjects, attenuating postprandial glycemia.
Adam M Deane, Nam Q Nguyen, +8 authors, Michael Horowitz.
J Clin Endocrinol Metab, 2009 Nov 07; 95(1). PMID: 19892837
Glucagon-like peptide 1 (7-36 amide) secretion in response to luminal sucrose from the upper and lower gut. A study using alpha-glucosidase inhibition (acarbose).
C Qualmann, M A Nauck, +2 authors, W Creutzfeldt.
Scand J Gastroenterol, 1995 Sep 01; 30(9). PMID: 8578189
D-xylose testing.
R M Craig, E D Ehrenpreis.
J Clin Gastroenterol, 1999 Sep 09; 29(2). PMID: 10478874
Effect of blood sampling schedule and method of calculating the area under the curve on validity and precision of glycaemic index values.
Thomas M S Wolever.
Br J Nutr, 2004 Feb 06; 91(2). PMID: 14756916
Reduced incretin effect in type 2 (non-insulin-dependent) diabetes.
M Nauck, F Stöckmann, R Ebert, W Creutzfeldt.
Diabetologia, 1986 Jan 01; 29(1). PMID: 3514343
Highly Cited.
Postprandial hyperglycemia and glycemic variability: should we care?
Eberhard Standl, Oliver Schnell, Antonio Ceriello.
Diabetes Care, 2011 May 06; 34 Suppl 2. PMID: 21525442    Free PMC article.
The incretin system and its role in type 2 diabetes mellitus.
Jens Juul Holst, Tina Vilsbøll, Carolyn F Deacon.
Mol Cell Endocrinol, 2008 Sep 13; 297(1-2). PMID: 18786605
Highly Cited. Review.
The physiological role of GLP-1 in human: incretin, ileal brake or more?
Jörg Schirra, Burkhard Göke.
Regul Pept, 2005 Mar 23; 128(2). PMID: 15780430
Protein 'pre-loads' in type 2 diabetes: what do we know and what do we need to find out?
Christopher K Rayner, Jing Ma, +2 authors, Michael Horowitz.
Diabetologia, 2014 Oct 15; 57(12). PMID: 25312814
Effect of a low dose whey/guar preload on glycemic control in people with type 2 diabetes--a randomised controlled trial.
Peter M Clifton, Claire Galbraith, Leah Coles.
Nutr J, 2014 Oct 26; 13. PMID: 25343850    Free PMC article.
Gastric emptying and glycaemia in health and diabetes mellitus.
Liza K Phillips, Adam M Deane, +2 authors, Michael Horowitz.
Nat Rev Endocrinol, 2014 Nov 26; 11(2). PMID: 25421372
Postprandial insulin and glucose levels are reduced in healthy subjects when a standardised breakfast meal is supplemented with a filtered sugarcane molasses concentrate.
Timothy P Ellis, Alison G Wright, Peter M Clifton, Leodevico L Ilag.
Eur J Nutr, 2015 Sep 28; 55(8). PMID: 26410392
Whey protein: The "whey" forward for treatment of type 2 diabetes?
Linda E Mignone, Tongzhi Wu, Michael Horowitz, Christopher K Rayner.
World J Diabetes, 2015 Oct 31; 6(14). PMID: 26516411    Free PMC article.
Interventions That Affect Gastrointestinal Motility in Hospitalized Adult Patients: A Systematic Review and Meta-Analysis of Double-Blind Placebo-Controlled Randomized Trials.
Varsha M Asrani, Harry D Yoon, +2 authors, Maxim S Petrov.
Medicine (Baltimore), 2016 Feb 06; 95(5). PMID: 26844455    Free PMC article.
Systematic Review.
Improved glucose regulation in type 2 diabetic patients with DPP-4 inhibitors: focus on alpha and beta cell function and lipid metabolism.
Bo Ahrén, James E Foley.
Diabetologia, 2016 Feb 20; 59(5). PMID: 26894277
Effect of a macronutrient preload on blood glucose level and pregnancy outcome in gestational diabetes.
Li Li, Jing Xu, +8 authors, Jian Wang.
J Clin Transl Endocrinol, 2016 May 16; 5. PMID: 29067233    Free PMC article.
Xylose: absorption, fermentation, and post-absorptive metabolism in the pig.
Nichole F Huntley, John F Patience.
J Anim Sci Biotechnol, 2018 Jan 18; 9. PMID: 29340150    Free PMC article.
Role of Intestinal Bitter Sensing in Enteroendocrine Hormone Secretion and Metabolic Control.
Cong Xie, Xuyi Wang, +3 authors, Tongzhi Wu.
Front Endocrinol (Lausanne), 2018 Oct 16; 9. PMID: 30319553    Free PMC article.
Non-nutritive Sweeteners and Glycaemic Control.
Yoona Kim, Jennifer B Keogh, Peter M Clifton.
Curr Atheroscler Rep, 2019 Nov 20; 21(12). PMID: 31741078
Diabetic Gastroparesis and Glycaemic Control.
Ryan Jalleh, Chinmay S Marathe, +2 authors, Michael Horowitz.
Curr Diab Rep, 2019 Dec 04; 19(12). PMID: 31792708
Relationship between diet/exercise and pharmacotherapy to enhance the GLP-1 levels in type 2 diabetes.
Yuki Fujiwara, Shunsuke Eguchi, +4 authors, Kinsuke Tsuda.
Endocrinol Diabetes Metab, 2019 Jul 12; 2(3). PMID: 31294084    Free PMC article.
1-Kestose supplementation mitigates the progressive deterioration of glucose metabolism in type 2 diabetes OLETF rats.
Ayako Watanabe, Yoshihiro Kadota, +4 authors, Yasuyuki Kitaura.
Sci Rep, 2020 Sep 26; 10(1). PMID: 32973311    Free PMC article.
Enteroendocrine Hormone Secretion and Metabolic Control: Importance of the Region of the Gut Stimulation.
Cong Xie, Karen L Jones, Christopher K Rayner, Tongzhi Wu.
Pharmaceutics, 2020 Aug 23; 12(9). PMID: 32825608    Free PMC article.
Energy Expenditure, Carbohydrate Oxidation and Appetitive Responses to Sucrose or Sucralose in Humans: A Pilot Study.
Christine Chern, Sze-Yen Tan.
Nutrients, 2019 Aug 04; 11(8). PMID: 31374985    Free PMC article.
Chemical exchange sensitive MRI of glucose uptake using xylose as a contrast agent.
Jicheng Wang, Mitsuhiro Fukuda, +2 authors, Tao Jin.
Magn Reson Med, 2020 Oct 28; 85(4). PMID: 33107108    Free PMC article.
Gastrointestinal Distension by Pectin-Containing Carbonated Solution Suppresses Food Intake and Enhances Glucose Tolerance via GLP-1 Secretion and Vagal Afferent Activation.
Kento Ohbayashi, Yukiko Oyama, +3 authors, Yusaku Iwasaki.
Front Endocrinol (Lausanne), 2021 Jun 26; 12. PMID: 34168616    Free PMC article.
Gastric emptying of solutions containing the natural sweetener erythritol and effects on gut hormone secretion in humans: A pilot dose-ranging study.
Bettina K Wölnerhanssen, Jürgen Drewe, +9 authors, Anne C Meyer-Gerspach.
Diabetes Obes Metab, 2021 Feb 11; 23(6). PMID: 33565706    Free PMC article.