Horm Metab Res 2017; 49(11): 886-891
DOI: 10.1055/s-0043-119089
Endocrine Care
© Georg Thieme Verlag KG Stuttgart · New York

Effect of Butyrate and Inulin Supplementation on Glycemic Status, Lipid Profile and Glucagon-Like Peptide 1 Level in Patients with Type 2 Diabetes: A Randomized Double-Blind, Placebo-Controlled Trial

Neda Roshanravan
1   Nutrition Research Center, Students Research Committee, School of Nutrition, Tabriz University of Medical Science, Tabriz, Iran
Reza Mahdavi
2   Nutrition Research Center, School of Nutrition, Tabriz University of Medical Science, Tabriz, Iran
Effat Alizadeh
3   Department of Medical Biotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Science, Tabriz, Iran
Mohammad Asghari Jafarabadi
4   Road Traffic Injury Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
5   Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran
Mehdi Hedayati
6   Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Abed Ghavami
2   Nutrition Research Center, School of Nutrition, Tabriz University of Medical Science, Tabriz, Iran
Shahriar Alipour
7   Department of Molecular Medicine, Nutrition Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Naimeh Mesri Alamdari
8   Student Research Committee, School of Health, Iran University of Medical Science, Tehran, Iran
Meisam Barati
2   Nutrition Research Center, School of Nutrition, Tabriz University of Medical Science, Tabriz, Iran
Alireza Ostadrahimi
2   Nutrition Research Center, School of Nutrition, Tabriz University of Medical Science, Tabriz, Iran
› Author Affiliations
Further Information

Publication History

received 05 March 2017

accepted 29 August 2017

Publication Date:
29 September 2017 (online)


Studies on humans with diabetes mellitus showed that the crosstalk between the intestinal microbiota and the host has a key role in controlling the disease. The aim of this study was to evaluate the effects of sodium butyrate and high performance inulin supplementation simultaneously or singly on glycemic status, lipid profile, and glucagon-like peptide 1 level in adults with type 2 diabetes mellitus. Sixty patients were recruited for the study. The participants were randomly allocated, using randomized block procedure, to one of the four treatment groups (A, B, C, or D). Group A received sodium butyrate capsules, group B received inulin supplement powder, group C was exposed to the concomitant use of inulin and sodium butyrate, and group D consumed placebo for 45 consecutive days. Markers of glycemia, lipid profile, and glucagon-like peptide 1 were measured pre- and post-intervention. Dietary supplementation in groups A, B, and C significantly reduced diastolic blood pressure in comparison with the placebo group (p<0.05). Also, intra-group statistical analysis showed that only treatment with sodium butyrate + inulin (group C) significantly reduced fasting blood sugar (p=0.049) and waist to hip ratio (p=0.020). Waist circumference in groups B and C reduced significantly after the intervention (p=0.007 and p=0.011; respectively). The post hoc Tukey tests showed significant increase in glucagon-like peptide 1 concentration in groups A and C in comparison with group D (p<0.05). The results suggest that inulin supplementation may be useful to diabetic patients and these effects could be increased with butyrate supplement.

Supplementary Material

  • References

  • 1 Ruan Y, Sun J, He J, Chen F, Chen R, Chen H. Effect of probiotics on glycemic control: A systematic review and meta-analysis of randomized, controlled trials. PloS one 2015; 10: e0132121
  • 2 Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes estimates for the year 2000 and projections for 2030. Diabetes Care 2004; 27: 1047-1053
  • 3 Melli L, do Carmo-Rodrigues M, Araújo-Filho H, Solé D, de Morais M. Intestinal microbiota and allergic diseases: A systematic review. Allergol Immunopathol 2016; 44: 177-188
  • 4 Le Barz M, Anhê FF, Varin TV, Desjardins Y, Levy E, Roy D, Urdaci MC, Marette A. Probiotics as complementary treatment for metabolic disorders. Diabetes metab J 2015; 39: 291-303
  • 5 Ericsson AC, Franklin CL. Manipulating the gut microbiota: Methods and challenges. ILAR J 2015; 56: 205-217
  • 6 Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, Morelli L, Canani RB, Flint HJ, Salminen S. Expert consensus document: The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol 2014; 11: 506-514
  • 7 Pineiro M, Asp N-G, Reid G, Macfarlane S, Morelli L, Brunser O, Tuohy K. FAO Technical meeting on prebiotics. J Clin Gastroenterol 2008; 42: S156-S159
  • 8 de Vrese M, Schrezenmeir J. Probiotics, prebiotics, and synbiotics. Adv Biochem Eng Biotechnol 2008; 111: 1-66
  • 9 Kolida S, Meyer D, Gibson G. A double-blind placebo-controlled study to establish the bifidogenic dose of inulin in healthy humans. Eur J Clin Nutr 2007; 61: 1189-1195
  • 10 Flamm G, Glinsmann W, Kritchevsky D, Prosky L, Roberfroid M. Inulin and oligofructose as dietary fiber: A review of the evidence. Crit Rev Food Sci Nutr 2001; 41: 353-362
  • 11 Kolida S, Gibson GR. Prebiotic capacity of inulin-type fructans. J Nutr 2007; 137: 2503S-2506S
  • 12 Schrezenmeir J, de Vrese M. Probiotics, prebiotics, and synbiotics—approaching a definition. Am J Clin Nutr 2001; 73: 361s-364s
  • 13 Cummings J, Pomare E, Branch W, Naylor C, Macfarlane G. Short chain fatty acids in human large intestine, portal, hepatic and venous blood. Gut 1987; 28: 1221-1227
  • 14 McIntyre A, Gibson P, Young G. Butyrate production from dietary fibre and protection against large bowel cancer in a rat model. Gut 1993; 34: 386-391
  • 15 Singh B, Halestrap AP, Paraskeva C. Butyrate can act as a stimulator of growth or inducer of apoptosis in human colonic epithelial cell lines depending on the presence of alternative energy sources. Carcinogenesis 1997; 18: 1265-1270
  • 16 Harig JM, Soergel KH, Komorowski RA, Wood CM. Treatment of diversion colitis with short-chain-fatty acid irrigation. N Engl J Med 1989; 320: 23-28
  • 17 Gao Z, Yin J, Zhang J, Ward RE, Martin RJ, Lefevre M, Cefalu WT, Ye J. Butyrate improves insulin sensitivity and increases energy expenditure in mice. Diabetes 2009; 58: 1509-1517
  • 18 Ahmad M, Krishnan S, Ramakrishna B, Mathan M, Pulimood A, Murthy S. Butyrate and glucose metabolism by colonocytes in experimental colitis in mice. Gut 2000; 46: 493-499
  • 19 Holst JJ. The physiology of glucagon-like peptide 1. Physiol Rev 2007; 87: 1409-1439
  • 20 Sa’ad H, Peppelenbosch MP, Roelofsen H, Vonk RJ, Venema K. Biological effects of propionic acid in humans; metabolism, potential applications and underlying mechanisms. Biochim Biophys Acta 2010; 1801: 1175-1183
  • 21 Hur KY, Lee M-S. Gut microbiota and metabolic disorders. Diabetes Metab J 2015; 39: 198-203
  • 22 Association AD. Diagnosis and classification of diabetes mellitus. Diabetes Care 2010; 33: S62-S69
  • 23 Dehghan P, Gargari BP, Asgharijafarabadi M. Effects of high performance inulin supplementation on glycemic status and lipid profile in women with type 2 diabetes: A randomized, placebo-controlled clinical trial. Health Promot Perspect 2013; 3: 55-63
  • 24 Dewulf EM, Cani PD, Claus SP, Fuentes S, Puylaert PG, Neyrinck AM, Bindels LB, de Vos WM, Gibson GR, Thissen J-P. Insight into the prebiotic concept: Lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Gut 2013; 62: 1112-1121
  • 25 Guess ND, Dornhorst A, Oliver N, Bell JD, Thomas EL, Frost GS. A randomized controlled trial: The effect of inulin on weight management and ectopic fat in subjects with prediabetes. Nutr Metab 2015; 12: 36-46
  • 26 Parnell JA, Reimer RA. Weight loss during oligofructose supplementation is associated with decreased ghrelin and increased peptide YY in overweight and obese adults. Am J Clin Nutr 2009; 89: 1751-1759
  • 27 Dehghan P, Gargari BP, Jafar-Abadi MA. Oligofructose-enriched inulin improves some inflammatory markers and metabolic endotoxemia in women with type 2 diabetes mellitus: A randomized controlled clinical trial. Nutrition 2014; 30: 418-423
  • 28 Fernandes R, do Rosario VA, Mocellin MC, Kuntz MG, Trindade EB. Effects of inulin-type fructans, galacto-oligosaccharides and related synbiotics on inflammatory markers in adult patients with overweight or obesity: A systematic review. Clin Nutr 2016; 113: 1-10
  • 29 Morel FB, Dai Q, Ni J, Thomas D, Parnet P, Fança-Berthon P. α-Galacto-oligosaccharides dose-dependently reduce appetite and decrease inflammation in overweight adults. J Nutr 2015; 145: 2052-2059
  • 30 Säemann MD, Böhmig GA, Österreicher CH, Burtscher H, Parolini O, Diakos C, Stöckl J, Hörl WH, Zlabinger GJ. Anti-inflammatory effects of sodium butyrate on human monocytes: Potent inhibition of IL-12 and up-regulation of IL-10 production. FASEB J 2000; 14: 2380-2382
  • 31 Cordel S, Dupas B, Douillard JY, Meflah K. Interleukin-2/sodium butyrate treatment cures rats bearing liver tumors after acquired 5-fluorouracil resistance. Int J Cancer 1998; 78: 735-739
  • 32 Krokowicz L, Stojcev Z, Kaczmarek BF, Kociemba W, Kaczmarek E, Walkowiak J, Krokowicz P, Drews M, Banasiewicz T. Microencapsulated sodium butyrate administered to patients with diverticulosis decreases incidence of diverticulitis—a prospective randomized study. Int J Colorectal Dis 2014; 29: 387-393
  • 33 Canani RB, Terrin G, Cirillo P, Castaldo G, Salvatore F, Cardillo G, Coruzzo A, Troncone R. Butyrate as an effective treatment of congenital chloride diarrhea. Gastroenterology 2004; 127: 630-634
  • 34 Wolever T, Brighenti F, Royall D, Jenkins AL, Jenkins DJ. Effect of rectal infusion of short chain fatty acids in human subjects. Am J Gastroenterol 1989; 84: 1027-1033
  • 35 Everard A, Belzer C, Geurts L, Ouwerkerk JP, Druart C, Bindels LB, Guiot Y, Derrien M, Muccioli GG, Delzenne NM. Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity. Proc Natl Acad Sci USA 2013; 110: 9066-9071
  • 36 Everard A, Lazarevic V, Derrien M, Girard M, Muccioli GG, Neyrinck AM, Possemiers S, Van Holle A, François P, de Vos WM. Responses of gut microbiota and glucose and lipid metabolism to prebiotics in genetic obese and diet-induced leptin-resistant mice. Diabetes 2011; 60: 2775-2786
  • 37 Kimura I, Ozawa K, Inoue D, Imamura T, Kimura K, Maeda T, Terasawa K, Kashihara D, Hirano K, Tani T. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43. Nat Commun 2013; 4: 1829-1841
  • 38 Causey JL, Feirtag JM, Gallaher DD. Effects of dietary inulin on serum lipids, blood glucose and the gastrointestinal environment in hypercholesterolemic men. Nutr Res 2000; 20: 191-201