Weight and glucose reduction observed with a combination of nutritional agents in rodent models does not translate to humans in a randomized clinical trial with healthy volunteers and subjects with type 2 diabetes

PLoS ONE

Volumn 11, Issue 4, 2016, Pages

  Hodge, Rebecca J ^a   Paulik, Mark A ^a,b   Walker, Ann ^a   Boucheron, Joyce A ^a   McMullen, Susan L ^a,c   Gillmor, Dawn S ^a,d   Nunez, Derek J ^a  

^a GLAXOSMITHKLINE   (United States)

^b Research Triangle   (United States)

^c PAREXEL INTERNATIONAL   (United States)

^d Pharmaceutical Product Development   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALBUMIN ANTIBODY; ANTIDIABETIC AGENT; ANTIOBESITY AGENT; BLACK CURRANT EXTRACT; EXENDIN 4; FRUCTOSE OLIGOSACCHARIDE; GLUCOSE; GSK 457; HEMOGLOBIN A1C; LIRAGLUTIDE; METFORMIN; OLEIC ACID; PECTIN; PLACEBO; UNCLASSIFIED DRUG; BIOLOGICAL FACTOR; GLUCAGON LIKE PEPTIDE 1; GLUCOSE BLOOD LEVEL;

ABDOMINAL DISTENSION; ADULT; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CLINICAL ARTICLE; CONSTIPATION; CONTROLLED STUDY; DIARRHEA; DRUG BLOOD LEVEL; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG USE; ERUCTATION; FEMALE; FLATULENCE; GASTROINTESTINAL MOTILITY DISORDER; GLUCOSE METABOLISM; HUMAN; MALE; MOUSE; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OBESITY; PHARMACODYNAMICS; RANDOMIZED CONTROLLED TRIAL (TOPIC); SIDE EFFECT; SINGLE DRUG DOSE; UPPER ABDOMINAL PAIN; UPPER RESPIRATORY TRACT INFECTION; WEIGHT GAIN; WEIGHT REDUCTION; ADOLESCENT; AGED; ANIMAL; BLOOD; BODY WEIGHT; C57BL MOUSE; CLINICAL TRIAL; DRUG EFFECTS; GLUCOSE BLOOD LEVEL; METABOLISM; MIDDLE AGED; NORMAL HUMAN; PATHOPHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL; YOUNG ADULT;

ADOLESCENT; ADULT; AGED; ANIMALS; BIOLOGICAL FACTORS; BLOOD GLUCOSE; BODY WEIGHT; DIABETES MELLITUS, TYPE 2; FEMALE; GLUCAGON-LIKE PEPTIDE 1; HEALTHY VOLUNTEERS; HUMANS; HYPOGLYCEMIC AGENTS; LIRAGLUTIDE; MALE; METFORMIN; MICE; MICE, INBRED C57BL; MIDDLE AGED; WEIGHT LOSS; YOUNG ADULT;

EID: 84964597651     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0153151     Document Type: Article

References (36)

1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384(9945):766-81. PMID: 24880830
2. NIH Publication No. 98-4083. Health Risks of Overweight and Obesity. Clinical Guidelines on the Identification, Evaluation, and Treatment of Overweight and Obesity in Adults-The Evidence Report. Sep 1998: 12-25.
3. Cani PD, Everard A, Duparc T. Gut microbiota, enteroendocrine functions and metabolism. Curt Opin Pharmacol. 2013; 13;935-40.
4. Everard A, Cani PD, Diabetes, obesity, and gut microbiota. Best Prac Res Clin Gastroenterol. 2013; 27(1):73-83.
5. Ley RE, Blackhed F, Turnbaugh P, Lozupone CA, Knight RD, Gordon JI. Obesity alters gut microbial ecology. Proc Nat Acad Sci. 2005; 102(31):11070-75. PMID: 16033867
6. Cani PD, Bibiloni R, Knauf C, Waget A, Neyrinck AM, Delzenne NM, et al. Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced Inflammation in High-Fat Diet-Induced Obesity and Diabetes in Mice. Diabetes. 2008; 57(6):1470-81. doi: 10.2337/db07-1403 PMID: 18305141
7. Cani PD, Possemiers S, Van de WT, Guiot Y, Everard A, Rottier O, et al. Changes in gut microbiota control inflammation in obese mice through a mechanism involving GLP-2-driven improvement of gut permeability. Gut. 2009; 58:1091-1103. doi: 10.1136/gut.2008.165886 PMID: 19240062
8. Janssen S, Deportere I. Nutrient sensing in the gut: new roads to therapeutics? Trends Endocrinol Metab. 2013; 24(2):92-100. doi: 10.1016/j.tem.2012.11.006 PMID: 23266105
9. Den Besten G, van Eunen K, Groen AK, Venema K, Reijingoud D-J, Bakker BM. The role of short-chain fatty acids in the interplay between diet, gut microbiota, and host energy metabolism. J Lipid Res. 2013; 54:2325-40. doi: 10.1194/jlr.R036012 PMID: 23821742
10. Puddu A, Sanguineti R, Montecucco F, Viviani GL. Evidence for the Gut Microbiota Short-Chain Fatty Acids as Key Pathophysiological Molecules Improving Diabetes. Mediators Inflamm. 2014: Article ID 162021, 9 pages, 2014. doi: 10.1155/2014/162021
11. Moran TH. Gut peptides in the control of food intake. Int J Obes. 2009; 33:S7-S10.
12. Karra E, Batterham RL. The role of gut hormones in the regulation of body weight and energy homeostasis. Mol Cell Endocrinol. 2010; 316(2):120-8. doi: 10.1016/j.mce.2009.06.010 PMID: 19563862
13. Inzucchi SE, Bergenstal RM, Buse JB, Diamant M, Ferranini E, Nauck M, et al. Management of Hyperglycemia in Type 2 Diabetes 2015-A Patient-Centered Approach. Diabetes Care. 2015; 38:140-9.
14. Astrup A, Rossner S, van Gaal L, Rissanen A, Niskanen L, al Hakim M, et al. Effects of liraglutide in the treatment of obesity: a randomized, double-blind, placebo-controlled study. Lancet. 2009; 374 (9701):1606-16.
15. Therakan G, Tan T, Bloom S. Emerging therapies in the treatment of'diabesity': beyond GLP-1. Trends Pharmacol Sci. 2011; 32(1):8-15.
16. Napolitano A, Miller S, Nicholls AW, Baker D, van Horn S, Thomas E, et al. Novel Gut-Based Pharmacology of Metformin in Patients with Type 2 Diabetes Mellitus. PLOS One. 2014; 9(7): e100778. doi: 10.1371/journal.pone.0100778 PMID: 24988476
17. International Conference on Harmonisation (1996) ICH Harmonised Tripartite Guideline. Guideline for Good Clinical Practice. Version 10.
18. World Medical Association (2000) Declaration of Helsinki: ethical principles for medical research involving human subjects. J Am Med Assoc. 284:3043-45.
19. Svedlund J., Sjodin I, Dolevall G. GSRS - a clinical rating scale for gastrointestinal symptoms in patients with irritable bowel syndrome and peptic ulcerdisease. Dig. Dis. Sci. 1988; 33:129-134. PMID: 3123181
20. 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; 89:1751-59. doi: 10.3945/ajcn.2009.27465 PMID: 19386741
21. DiLorenzo C, Williams CM, Hajnal F, Valenzuela JE. Pectin delays Gastric Emptying and Increases Satiety in Obese Subjects. Gastroenterol. 1988: 95(5):1211-15.
22. Schwartz SE, Levine RA, Weinstock RS, Petokas S, Mills CA, Thomas FD. Sustained pectin ingestion: effect on gastric emptying and glucose tolerance in non-insulin-dependent diabetic patients. Am J Clin Nutr. 1988; 48:1413-17. PMID: 2849298
23. Carr RD, Larsen MO, Winzell MS, Jelic K, Lindgren O, Deacon CF, et al. Incretin and islet hormonal responses to fat and protein ingestion in healthy men. Am J Physiol Endocrinol Metab. 2008; 295: E779-E784. doi: 10.1152/ajpendo.90233.2008 PMID: 18612044
24. Teres S, Barcelo-Coblijn G, Benet M, Alvarez R, Bressani R, Halver JE, et al. Oleic acid content is responsible for the reduction in blood pressure induced by olive oil. PNAs. 2008; 105(37):13811-16. doi: 10.1073/pnas.0807500105 PMID: 18772370
25. Munir KM, Chandrasekaran S, Gao F, Quon MJ. Mechanisms for food polyphenols to ameliorate insulin resistance and endothelial dysfunction: therapeutic implications for diabetes and its cardiovascular complications. Am J Physiol Endorcinol Metab. 2013: 305(6):E679-E686.
26. Guo H, Xia M, Zou T, Ling W, Zhong R, Zhang W. Cyanidin 3-glucoside attenuates obesity-associated insulin resistance and hepatic steatosis in high-fat diet-fed and db/db mice via the transcription factor Fox01. J Nutr Biochem. 2012; 23(4):349-60.
27. Tsuda T. Regulation of Adipocyte Function by Anthocyanins; Possibility of Preventing the Metabolic Syndrome. J. Agric. Food Chem. 2008; 56:642-46. doi: 10.1021/jf073113b PMID: 18211021
28. Delzenne NM, Cani PD, Daubioul C, Neyrinck AM. Impact of inulin and oligofructose on gastrointestinal peptides. Br J Nutr. 2005; 93(Suppl. 1):S157-S161. PMID: 15877889
29. Gibson GR, Beatty ER, Wang X, Cummings JH. Selective stimulation of bifidobacteria in the human colon by oligofructose and inulin. Gastroenterol. 1995; 108(4):975-982.
30. Howard MD, Gordon DT, Garleb KA, Kerley MS. Dietary fructooligosaccharide, xylooligosaccharide and gum arabic have variable effects on cecal and colonic microbiota and epithelial cell proliferation in mice and rats. J Nutr. 1995; 125(10):2604-2609. PMID: 7562096
31. Kleessen B, Hartmann L, Blaut M. Oligofructose and long-chain inulin: Influence on the gut microbial ecology of rats associated with a human faecal flora. Bri J Nutri. 2001; 86(2):291-300.
32. Sasaki R, Nishimura N, Hoshino H, Isa Y, Kadowaki M, Ichi T, et al. Cyanidin 3-glucoside ameliorates hyperglycemia and insulin sensitivity due to downregulation of retinol binding protein 4 expression in diabetic mice. Biochem Pharmacol. 2007; 74:1619-1627. PMID: 17869225
33. Burant CF. Activation of GPR40 as a Therapeutic Target for the Treatment of Type 2 Diabetes. Diabetes Care. 2013; 36(S2):S175-S179.
34. Zhang D, Leung PS. Potential roles of GPR120 and its agonists in the management of diabetes. Drug Des, Devel Ther. 2014; 8:1013-1027.
35. Chakravarthy MV, Lodhi IF, Yin L, Malapaka RRV, Xu HE, Turk J, et al. Identification of a Physiologically Relevant Endogenous Ligand for PPARα in Liver. Cell. 2009; 138(3):476-488.
36. Godlewski G, Offertaler L, Wagner JA, Kunos G. Receptors for acylethanoloamides-GPR55and GPR119. Prostaglandins Other Lipid Mediat. 2009; 89(3-4):105-111. doi: 10.1016/j.prostaglandins.2009.07.001 PMID: 19615459