Effect of Palatable Soluble Fibre-Containing Carbohydrate Foods on
Transcription
Effect of Palatable Soluble Fibre-Containing Carbohydrate Foods on
MolecularNutritionandFoodTechnology EffectofPalatableSolubleFibre-ContainingCarbohydrateFoodson PostprandialBloodGlucoseResponseinHealthyIndividuals MasterofScienceThesisby TajaKarner May2016 DepartmentofFoodScience MolecularNutritionandFoodTechnology EffectofPalatableSolubleFibre-ContainingCarbohydrateFoodsonPostprandialBlood GlucoseResponseinHealthyIndividuals MasterofScienceThesis(60ECTS) TajaKarner(201403218) Supervisor: PerBendixJeppesen AssociateProf.,PhD DepartmentofClinicalMedicine AarhusUniversity May2016 PREFACE ThisthesisrepresentsthefinalworkofmyMasterdegreeinMolecularnutritionandfood technology at Aarhus University, Denmark. The experiment work was done in Toronto, Canada between September 2015 – March 2016 at Risk Factor Modification Center at St. Michael Hospital, Toronto. The supervisor that guide me through my work and make it possibleformetoexpandmyknowledgeinCanadaisAssociateProfessor,PhD,PerBendix Jeppesen.InTorontoIwasguidedbyco-supervisorDr.MDVladimirVuksan. Acknowledge IwouldiketothankmysupervisorPerBendixJeppesentohelpmefindtheprojectIwished to work on and introduce me to the opportunity in Toronto. I also want to thank him for guidingmethroughtheprocessofwritingamasterthesisreport.SpecialthankgoestoDr. MD Vladimir Vuksan that trust in me and offer me to do the research in their lab and for sharingwithmehisknowledge.Thankyouforintroducingmetothefieldofsearchingfor foodimprovementstohelpdiabeticpatientsmaintaintheirhealth.Furthermore,Iwantto thankElenaJovanovski,MSc.PhDforguidingmethrougheverystepandhelpingmeclarify allthequestionsthatpopuptomymind.ThanksalsoRodneyAuYeungforhelpingmewith patients,statisticsandtakingcareaboutresearchmaterialandfacilitiesthatweusedinthe experiment. Iwouldliketothankthecollegesinthelabfortryingallmybakedfoodevenwhentheywere notbakedsuccessfully.SpecialthankgoestoAny,Rana,Nourah,CarmenandJuliaforthe excellentworkingatmospheretheycreated. Manythanksgotomyparents,brothersandwholefamilythatsupportmeonmyjourney andhelpmefinanciallytomakethiseducationevenpossible.Thankyoutomybestfriend UrskatocheermeupwhenIwasstressedandtoallmyfriendsandthatstoodbymyside duringtheproject. LISTOFPUBLICATIONS Thisthesisconsistsoftwoparts: 1) Reviewondiabetesandeffectofviscoussolubledietaryfibreonglycaemia. 2) ScientificpaperregardingmystudyperformedinToronto,entitle: Effect of Palatable Soluble Fibre-Containing Carbohydrate Foods on Postprandial Blood Glucose ResponseinHealthyIndividuals:ARandomized,Controlled,Double-blindedStudy ByVladimirVuksan,TajaKarner,AmandaMa,ElenaJovanovski,FeiAuYeung 4 LISTOFABBREVIATIONS ADA:AmericanDiabeticAssociation AUC:Areaunderthecurve BMI:Bodymassindex CHO:Carbohydrates CVD:Cardiovasculardisease FFA:Freefattyacids GI:Glycemicindex GLUT:Glucosetransporterproteins GM:Glucomannan IRS:Insulinreceptorsubstrate ISF:Insolublefibre LADA:LatentAutoimmuneDiabetesinAdults MS:Metabolicsyndrome NEFA:Non-esterifiedfattyacid,equaltoFFA:Freefattyacid PGX:PolyGlycompleX SCFA:Short-chainfattyacid SF:Solublefibre T1D:Type1Diabetes T2D:Type2Diabetes VFB:Viscousfibreblend VSF:Viscoussolublefibre WG:Wholegrain WHO:WorldHealthOrganization 5 TABLEOFCONTENTS PREFACE.........................................................................................................................................3 LISTOFPUBLICATIONS...................................................................................................................4 LISTOFABBREVIATIONS.................................................................................................................5 TABLEOFCONTENTS......................................................................................................................6 ABSTRACT......................................................................................................................................7 INTRODUCTION..............................................................................................................................8 BACKGROUND..............................................................................................................................10 1. DIABETES..................................................................................................................................10 1.1. Epidemiologyofdiabetes.................................................................................................10 1.2. Type2diabetes................................................................................................................11 1.3. Overviewofglucosemetabolism.....................................................................................12 1.4. PathophysiologyofT2D....................................................................................................13 1.4.1. 1.4.2. 1.4.3. Abdominalobesity......................................................................................................................................13 Insulinresistance.........................................................................................................................................14 Hyperglycemia.............................................................................................................................................15 2. CARBOHYDRATES.....................................................................................................................17 3. DIETARYFIBRE..........................................................................................................................18 3.1. Definition..........................................................................................................................18 3.2. Dietaryfibreclassifications...............................................................................................18 3.3. Dietaryfibreandfoodprocessing....................................................................................20 3.4. Dietaryfibrerecommendations.......................................................................................20 WHOLEGRAINSHEALTHEFFECTS.................................................................................................22 VISCOUSSOLUBLEFIBRE...............................................................................................................23 1. Viscoussolublefibresupplementation................................................................................23 1.1. KonjacGlucomannan........................................................................................................24 1.1.1. PolysaccharideComplex(PGX)...............................................................................................................26 1.1.1.1. PGXhealthclaims...........................................................................................................................27 1.1.1.2. IncorporatingPGXintodifferentfoodmatrices.............................................................................27 MYMASTERTHESISPROJECT........................................................................................................29 CONCLUSION................................................................................................................................32 PERSPECTIVE................................................................................................................................33 BIBLIOGRAPHY.............................................................................................................................34 6 ABSTRACT Background:Increaseofdietaryfibreintakeandimprovementofpostprandialglucoseresponsecould be achieved with fibre-enriched carbohydrate products. To evaluate PGX fibre’s incorporation, sensory assessment for palatability and effect on post-prandial glycemic response of enriched productswasobservedinhealthyindividuals. Methods:Thestudyconsistedoftwophases.PhaseI:twenty-onehealthyindividuals(mean±SEM, age:25.2±9years,bodymassindex[BMI]:22.5±2.4kg/m2)assessedpalatabilitydifferencebetween control and treatment products using sensory evaluation questionnaires. Phase II: twenty healthy participants(mean±SEM,age:26.3±10years,BMI:22.4±3.6kg/m2)wererandomizedtoreceive whitebread,muffins,mashedpotatoesandcreamofwheatafterovernightfastingoneightseparate occasions. All products consisted of 50 g of available carbohydrates and were either implemented with4gofPGXorusedascontrol.Bloodglucosesamplesandsatietyratingswerecollectedatfasting andover2hourspostprandial. Results:IncorporationofPGXresultsinnodecreaseinpalatabilityfor3outof4foodproducts.There wasnosignificantreductioniniAUCforanyoftheproductseparately,howeverasignificantreduction was observed in pooled non-baked products, mashed potatoes and cream of wheat, compared to control attributes. Peak rises in glucose concentrations were significantly lower for treatment productscomparedwiththeirrefinedcounterparts. Conclusions: Addition of VFB to different food matrices must be considered and evaluated on individualbasisbeforeanyconclusionscanbeformedonitsglycaemiareducingpotential. 7 INTRODUCTION At one hand the general quality of life in past decades is increasing with technology improvement,butontheotherhandwearefacingaveryconcernincreaseofchronicdiseases globally. Lifestyle changes that include decrease of physical activity and increased consumptionofhighlyprocessedfoodhavebeenreflectedinmanymetabolicdysfunctions knownbythetermmetabolicsyndrome(MS)(WHO2003).MSishighlyconnectedtotherisk ofdevelopingtype2diabetes(T2D)andcardiovasculardisease(CVD)thataretwodominantly chronicaldiseasesnowadays(Singhetal.2013).T2Disoneofthediseaseswiththehugest increase in incidents in the past decades (Ezzati 2016). The prevalence for T2D was firstly connected to developed countries, however in the last decade much faster growth of incidentsofT2Disobservedindevelopingcountries(WorldHealthOrganization2016).Even thoughT2Dusedtoberecognizedasdiseaseofelderpopulation,itisnowpresentalsoamong children(Dabelea2009). EventhoughT2Disassociatedwithgeneticpredisposition,environmentfactorsandlifestyle playsignificantroleandoffereffectiveapproachestopreventfromitsdevelopment(Lam& LeRoith2012).However,theapproachesareverygeneralandincludetakingcareforoverall healthwithregularexercise,healthyfood,avoidingsmokingandhavingbloodpressureand lipidlevelindesirablerange(WorldHealthOrganization2016).Themainrecommendations of World Health Organization for preventing T2D and its complications include having sufficient dietary fibre (DF) intake with consumption of whole grains (WG), legumes, vegetablesandfruitsandlimitedintakeofsaturatedfatandsugartobelow10%ofdaily caloric intake, separately (Ahmad et al. 2001). However, despite the recommendations dietaryfibreintakeremainlowerthandesirable(Association2008). Duetomodernlifestylepeoplefindrecommendationhardtofollow,thereforealotofeffort isputintoseekingofnewsolutionstohelppeoplemaintainoverallhealth.Additionoffibre intodifferentfoodproductshasbeenapracticefordecades,howevermostoftheproducts areenrichedwithinsolublefibrewhichdonotofferdesirableloweringofpostprandialblood glucose that has been recognized as crucial parameter in diabetes control (Frontoni et al. 8 2013). Moreover, most of fibre-enriched products are associated with decrease of palatability,thereforerefinedproducts,despiteawarenessoflownutritionalvalue,remain general preference (Association 2008). Understanding of physicochemical properties of differentfibreandtheireffectsonglucosemetabolismisapromisingwaytoimprovefood productsavailableonthemarket(Guillon&Champ2000).Previousresultshaveshownthat the most significant reduction of postprandial glycaemia of carbohydrate foods can be achieved with viscous soluble fibre implementation (Jenkins et al. 1978). However, high viscosity does reflect in reduced palatability and therefore ways of implementing viscous solublefibreincommonlyconsumedfoodwithoutaffectingtheirpalatabilityarestillsought. Theaimofthismasterthesisistoevaluatepreviousstudiesonhowviscoussolublefibrecan improve post-prandial glycaemia and help to control blood glucose level and how their incorporationinfoodproductscaninfluencedietaryfibreintakeandimprovediabetesrates. 9 BACKGROUND 1. DIABETES 1.1. Epidemiologyofdiabetes Diabetesisconsidertobethemostrepresentedendocrinechronicdiseaseintheworld(J.E. Shaw et al. 2010). In 1980 there were 108 million reported diabetic people in the world, whereasin2014thisnumberhasincreaseupto422million.Theincreaseratecorrespondto therisefrom5.7%to8.5%adultpopulationhavingdiabetes(WorldHealthOrganization 2016).Type2diabetesisthemostcommontypeofdiabetesandcontributetoaround90% ofalldiagnoseddiabetescasesworldwideandto80%ofalldiabeticpatientsinDenmark(J.E. Shawetal.2010).It’swellestablishedthatthecauseofthedefectisacombinationofgenetic predisposition and environmental factors. In a contrast to type 1 diabetes (T1D) where a geneticpredispositionplaysacriticalrole,T2Dismorerelatedtomanyenvironmentalfactors andthereforeeasiertoprevent(Scheen2003).IncaseofT1D,autoimmuneresponseofa body reflects in disruption of pancreatic beta-cells and it is being cured with insulin substitution.Itoccursinchildhoodandprogressthroughyears(Drouinetal.2009).Itwas assumedthatonlytwoformsofdiabetesexist,howeverthereareotherlesscommonforms. Oneofthemistype1½diabetesorLADA(LatentAutoimmuneDiabetesinAdults)thatoccurs inadultagesbuthavethesamemaincharacteristicsasT1D(Fourlanosetal.2005).Itisan autoimmunediseaseanditneedsaninsulinsupplywhichusuallyhastobeincreasedover years. The fourth type is called gestational diabetes and can occur during pregnancy of overweight or obese women (Buchanan & Xiang 2005; Jensen et al. 1999). Abdominal fat cause decrease of insulin sensitivity which can be harmful for fetus if not controlled with healthierlifestyleorinsomecaseseveninsulinisneeded(Langeretal.2005).Themainfocus of this background is going to be T2D since it is the most common and preventable with dietarychangeslikeincreasingfibreconsumption. 10 1.2. Type2diabetes Type2diabetesisacomplexchronicconditionwheninsufficientinsulinproductionaswellas insulinsensitivityleadstoincreaseofbloodglucoselevels(Kahn2003).T2Disadiseasethat doesnotoccurovernightandcannotbelinkedtooneparticulardysfunctioninthebody.At thepointofdiagnosis,mostoftheabnormalitiesareusuallyalreadypresent,thereforethe primarycauseishardtoestablish.Itsprogressionisslowandoftenpre-diabeticphase,an intermediatehyperglycemiastage,canlastcoupleofdecadesbeforethefull-blowndiabetes occur (Saini 2010; The Expert Committee on the Diagnosis and Classification of Diabetes Mellitus2003).ThediagnosisofT2Dhavetobedoneontwoseparateoccasionsandinclude fasting levels of plasma glucose at or above 7 mmol/L or if symptoms as weight loss and polyuria are present and casual plasma glucose concentration exceeded 11.1 mmol/L is considerasT2Dmarker(Fonseca2009). Due to its complexity the pathogenesis of T2D had been a debate for decades. Various disruptions of endocrine pancreas, liver, skeletal muscle, adipose tissue, central nervous system and guts may effect glucose metabolism and cause T2D if not treated preliminary (DEFRONZO 1988). Symptoms that may lead to T2D if not treated have been marked as metabolic syndrome and include obesity, hypertension, dyslipidemia, cardiovascular dysfunctionsandcoronaryarterydisease(Scheen2003).SincemostofthepeoplewithT2D sufferfromobesity,visceralfatadiposetissuesmostpossibleplayacrucialroleindisruption ofglucosehomeostasisbyelevatinginsulinresistanceinbothhepaticandmusculartissues (Kahn et al. 2006). Insufficient insulin sensitivity cause hyperglycemia and increase lipid formation, which leads in overproduction of insulin and potentially to failure of pancreas. Eventhoughtherearedrugsthattriggerinsulinsensitivity,losingweight,increasingphysical activityandavoidingglucoseelevationwithhealthydiethavebeenmoreeffectivewayto controlandavoidpreliminaryconsequencesofT2D(WorldHealthOrganization2016).For easierunderstandingofthemechanismbehindT2D,glucosemetabolismhastobediscussed. 11 1.3. Overviewofglucosemetabolism Glucoseistheprimarysourceofenergyforallthecellsinourbody,thereforethemechanism of regulating the amount of glucose available in plasma is very well controlled. The main hormonesthatcontrolglucoselevelareinsulinandglucagonthataresecretedfrompancreas (Zierler 1999). Pancreas is crucial organ in glucose metabolism and has an important endocrineaswellasdigestivefunction.Humanpancreasconsistsofapproximately1million isletsofLangerhansthatareproducingandsecretinghormonestoregulatethebehaviorof bodycellsandplayacriticalroleinprovidingenergyforallthecellsinhumanbody.Outof around3000cellsthatbuildsoneislets,48-59%arebeta-cellsand33-46%alpha-cellthat havethemajorendocrinefunctioninglucosemetabolism(Cabreraetal.2006).Aftermeal consumption the blood glucose level increase depending on the amount and type of carbohydrates consumed and the presence of fat and proteins in the meal (Jenkins et al. 1981).Afterinsulinissecreted,thephosphorylationcascadeoccurs,withIRSphosphorylation andinitiationofPI3K-AKTpathwaythatcausetheglucoseuptakeinthecell.Furthermore, intracellular glucose transporter type 4 (GLUT-4) with its translocation to the outer cell membrane enables the muscle and adipose tissue to uptake the glucose and store it as glycogen(Saltiel&Kahn2001).Theabsorptionofglucosethroughgutwallisenabledwith glucosetransporterproteins(GLUT-2)thattransportitintobeta-cells.Thatreflectsinseries ofreactionsthatincreaseATP/ADPratioandenclosedATP-regulatedK+channelswhichleads todepolarizationofplasmamembraneandincreaseofcytosolicfreeCa2+(Henquin2004). Thisstimulatesinsulinsecretionfrombeta-cellsthatisfurthertransportedtoliverandtothe bloodstreamwhereitisrecognizedbyinsulinreceptorsonthesurfaceofthecells.Receptors has to be previously activated with insulin receptor substrate-1 (IRS-1), the key signaling moleculethatinduceglucoseintakewhichreflectinloweringbloodglucoseconcentration (Choi&Kim2010).Inmuscleandlivercellstheglucoseisusedforshort-termenergystorage asaformofglycogen,theadiposetissuetaketheglucosefromplasmaandtransformittofat as a long-term energy reserve, whereas other cells break down the glucose to ATP via glycolysisandKrebscycleandusetheenergyforproteinsynthesisandothercellsfunctions (Saltiel&Kahn2001).Insulinsecretionalsoinfluencestheuptakeoffattyacids(FA)andamino acids(AA)andsuppressproductionofglucagon(Zierler1999).Glucagonisahormonewith oppositefunctionofinsuliniscalledglucagonandissecretedwhenbloodglucoselevelhas 12 fallenandneedstobeincreased.Inthissituation,glucagonstimulatesglycogenbreakdown toglucose(gluconeogenesis)sothatitisavailableforothercellstouseit(Exton1972). 1.4. PathophysiologyofT2D 1.4.1. Abdominalobesity ThemainclassificationofobesepeopleincludetheirBodymassindex(BMI)≥30kg/m2that iscalculatedasbodyweightdividedbysquaredheightinmeters.However,thisclassification doesnottakeintoconsiderationwheretheextrafatisstored.Ithasbeenestablishedthat vascular fat accumulated at intra-abdominal cause major complications correlated with obesity,whereassubcutaneousfatisnotsocritical(Carretal.2004).Toevaluatetheriskfor T2Ddiabetestheratiobetweenwaistandheightalsoneedstobeconsider(Ashwelletal. 2012). Abdominal obesity reflect in increase secretion of non-esterified fatty acids (also referredasfreefattyacids-FFA)andvariousotherpro-inflammatorymoleculesasleptin, tumornecrosisfactor(TNF)-α,resistin,adiponectinetc.thatinfluenceglucosemetabolism andpotentiallyleadtoinsulinresistanceasshownonFigure1(Montague&O’Rahilly2000; Kahnetal.2006).Eventhoughabdominalfatwasshowntoleadtoinflammationinthebody, lipotoxificationandoveractiveintravascularcoagulationfactors,clearcorrelationsbetween obesityanddevelopingofT2Dhavenotbeenshown(Kahnetal.2006). 13 Figure1:FactorsinfluencingdevelopingofT2D,adaptedfromScheen(Scheen2003). 1.4.2. Insulinresistance Eventhoughclearmechanismofhowobesitycontributetoinsulinresistanceisnottotally clarified,itiswellestablishedthatitisconnectedtoabnormalsecretionoffreefattyacids fromhypertrophiedadipocytetissueandthatbotharethemajorfactorindevelopingT2D (Kahnetal.2006).Asmentionbefore,productionofFFAisincreasedinoverweightpeople anditreflectsinabnormalitiesininsulin-signalingpathwayasshownonFigure2.Therecent hypothesisforinsulinresistanceasshownonFigure2includetheactofintracellularFFAon activationofserine/threoninekinasecascadewhichleadstoIRS-1phosphorylation(Shulman 2004).TheseinactivateIRS-1eventhoughtheinsulinispresentandconsequentlyPI3Kdoes notactivateglucosetransportationinthecell.Basedonthishypothesis,anyexceededlevel ofFFAinintracellularspacecaneventuallyleadtoinsulinresistanceofmuscleandlivercells andinducehyperglycemia(Shulman2004).Moreover,manysignalingandpro-inflammatory moleculeslikeTNF-αandinterleukin-6(IL-6)weresuggestedtoinfluencethesamepathway butindifferentsteps(Gaoetal.2002).Toconclude,insulinresistanceiscomplexstatethat iscausedbyexcessrateofFFAinintracellularspaceandoverproductionofpro-inflammatory cytokinesbymacrophagesandcontributetodecreaseoffattyacidoxidationthatleadsto lipotoxicity. 14 Figure 2: Mechanism of impaired insulin sensitivity by exceeded intra-cellular FFA concentrations.AdoptedfromShulman(Shulman2004). 1.4.3. Hyperglycemia In normal conditions, increase of glucose in blood stream induces the production and secretionofinsulinbypancreaticbeta-cellsthatstimulatemuscle,liverandadiposetissues inglucoseuptake.Incaseofinsulinresistance,thephosphorylationcascadestopsatanyof the previously mentioned steps and therefore excess glucose remain in the blood stream (hyperglycemia) (Saltiel & Kahn 2001). Many studies have demonstrated that defects in muscleglycogensynthesisplaycrucialroleinloweringinsulinsensitivity,sincethisshowsup to be the major pathway for glucose metabolism in the condition of hyperglycemia and hyperinsulinemia(Shulman2004).AsshownonFigure3,impairedmuscleinsulinsensitivity reflectsininactiveGLUT-4transporterandconsequentlyreductionofmusclescellsabilityof glucoseuptake(Samueletal.2010).Oftenhepaticgluconeogenesisisalsonotsuppressed whichleadtoadditionalelevationofglucoseconcentration.InthedevelopingstagesofT2D, insulinsensitivityisreducedandforsomeperiodthebodyisstillabletomaintainnormal glucoselevel,howeverovertimeinsulinsensitivitydrasticallydecreaseifnottreatedandlead to hyperglycemia. Since the insulin is not efficient, the beta-cells keeps producing high amount of insulin which over time leads to beta-cells dysfunction. Both lipotoxicity and hyperglycemiaarecorrelatedwithdecreaseofbeta-cellmassandfurthercomplicationsof diabetes(Reaven1988). 15 Figure3:Comparisonofmuscleglucosemechanisminnormalcells(left)andinthecaseof insulinresistance(right).AdoptedfromSamueletal(Samueletal.2010). ImportantmechanismfordevelopingT2Disrelatedalsotodyslipidemia,whichisdefinedas eitheroverlyincreasedleveloftriglycerides(TG)ordecreasedlevelofHDL-cholesterolbutit isnotgoingtobediscussedinthismasterthesis(Scheen2003). AllmentionedmechanismdefectsoccurinvariableproportionsinpatientswithT2Dandtheir degreeofcomplicationcanimproveovertimeiflifestylechangesaretakingintoaccount, otherwisethedysfunctionofmechanismincreasewithdiseaseprogression(Scheen2003). Oneofthelifestylechangesthatisrecommendedbymajorhealthagenciesandgovernment bodiesistheincreaseofdietaryfibreconsumption(Ahmadetal.2001).ItscorrelationtoT2D prevention and future opportunities for increasing their consumption are discussed in the nextchapters. 16 2. CARBOHYDRATES Carbohydrates(CHO)arethemostconsumedmacronutrientsgloballyandcontributeto40– 80 % of daily caloric intake, where lower range are referred to developed and higher to developingcountries(Burtonetal.2011).SinceT2Disdirectlyconnectiontocarbohydrate metabolism,itwasadebatefordecadeswhetherdifferenttypeofcarbohydratesplayarole in preventing or causing defects in glucose metabolism. Studies had shown that type of dietary carbohydrates and their quantity are both critical in causing obesity and other contributed chronic disease as T2D and cardiovascular dysfunction (Mann et al. 2007). Increase of T2D over the years was correlated with increase consumption of refined carbohydratesdepletedinfibrethatbroughtoutthehypothesisthatdietaryfibremaybean important parameter in blood glucose control (Mokdad et al. 2003). Those suggestions accelerated researchers to investigate carbohydrates metabolism and it was in 1981 that Jenkinsetalintroducedtheuseofglycemicindex(GI)toclassifydifferentcarbohydratefoods (Jenkinsetal.1981).GIrepresentsthepercentageofglucosethatappearinbloodstreamafter mealconsumptioncomparedtothereferencemealwhichisusuallyglucosesolutionorwhite bread.It’scalculatedasaratiobetweenareaunderthecurve(AUC)ofagivenmealdivided byAUCofareferencewithsameamountofavailableCHO(Jenkinsetal.1981).Themost significantfactorthatinfluenceglucoseavailabilityisthecontentofdietaryfibrewhichtend toimpedethehydrolysisofcarbohydratesinsmallintestinalandmaydecreasethediffusion rateofhydrolyticglucosethroughoutthegutlumen(D.J.A.Jenkinsetal.1987).Itseffect dependsonthetypeandquantityoffibre,howevertheoveralleffectoffibreonGIcannot be assumed only by fibre characteristic since it depends on many circumstances that are addressedinthenextsections(Jenkinsetal.1981). 17 3. DIETARYFIBRE 3.1. Definition Eventhoughthetermdietaryfibreisinusedformorethan50years,itsdefinitionhasbeena discussionfordecades.MostrecentCODEXdefinitionclassifiesdietaryfibreas: “Dietary fibre means carbohydrate polymers with ten or more monomeric units, which are not hydrolysed by the endogenous enzymes in the small intestine of humans and belong to the following categories’: —ediblecarbohydratepolymersnaturallyoccurringinthefoodasconsumed, —carbohydratepolymers,whichhavebeenobtainedfromfoodrawmaterialbyphysical, enzymaticorchemicalmeansandwhichhavebeenshowntohaveaphysiologicaleffectof benefittohealthasdemonstratedbygenerallyacceptedscientificevidencetocompetent authorities, —syntheticcarbohydratepolymerswhichhavebeenshowntohaveaphysiologicaleffectof benefittohealthasdemonstratedbygenerallyacceptedscientificevidencetocompetent authorities Footnote1:Whenderivedfromaplantorigin,dietaryfibremayincludefractionsofligninand/orother compoundsassociatedwithpolysaccharidesintheplantcellwalls.Thesecompoundsalsomaybemeasuredby certainanalyticalmethod(s)fordietaryfibre.” Footnote2:“Decisiononwhethertoincludecarbohydratesof3to9monomericunitsshouldbeleftupto nationalauthorities.”(Jones2014) In this definition are therefore included cell wall polysaccharides, lignin, resistant starch molecules and other minor components that have been shown to have beneficial physiologicaleffects(Mongeau&Brooks2016).Thecompositionandtheirbenefitsonhuman healthdifferfromitsoriginandphysiologicalproperties(Otles&Ozgoz2014). 3.2. Dietaryfibreclassifications Tounderstandandpredicthowspecificfibreinfluenceconsumers’healthmanythingshave tobeconsider.Duetohugevarietyoffibreaspartofhumandiet,itisnotpossibletolink 18 them to specific physiological effect without specifying and classifying them into different groups(Lattimer&Haub2010).MoststandardclassificationofDFisbasedontheirsolubility, even though it’s mainly focused on fibre’ chemical properties and does not help with understanding of physiological responses (Flamm et al. 2001). Firstly, it’s should be acknowledgedthatthedegreeofsolubilityinwatermaybedifferentthaningastrointestinal tractduetodifferentphysicalconditions(Guillon&Champ2000).Moreover,someoftheDF might be soluble in saliva but not in acidic conditions present in stomach (e.g. pectins) (Wanders et al. 2014). It was long believed that soluble fibre (SF) were not common in consumedfoodsbuttheydocontributetoonethirdoftotaldailyfibreintake(Mongeau& Brooks2016).SFaredissolvedinwaterandareabletoformgelswhichmakesthemslowly passingthroughsmallintestineandhighly-fermentedinlargeintestine.Ontheotherhand, insoluble fibre (ISF) cannot be dissolved in human gastrointestinal track and they act like bulking agent, but can only be fermented by bacteria to limited extend (Wong & Jenkins 2007). MoreimportantparametersthatbringusclosertounderstandingofDF’shealtheffectare physicochemical properties of fibre like viscosity and fermentability. Viscous soluble fibre (VSF) are able to thicken and have gelling properties when mixed with fluids, which as suggestedcanslowdowngastricemptingandabsorptionofnutrientsinsmallintestine.The mostresearchedVSFaregums,pectins,beta-glucansandKonjacGluccomannan.Degreeof gelling capacity depend on their chemical composition as well as food preparation (Schneeman1998;Dikeman&Fahey2006). Theextentoffermentabilitydependsonfibreproperties,butit’sassumedthat70-80%of totalDFintakearefermented,includingISFthathaslongbeenassumedtonotbefermented atall(Mongeau&Brooks2016).Fibrethatareeasilyfermentedareincreasingproductionof shortchainfattyacids(SCFAs)thathavebeenlinkedtomanyhealthbenefits.Whereas,fibre thatarefermentedslowlyorcannotbefermentedcompletelyactlikebulkingagentthatare beneficialforlaxationandincreasingstoolweight(Schneeman1998). 19 3.3. Dietaryfibreandfoodprocessing Afterunderstandingclassificationoffibrethatarebasedontheirchemicalcompositionand structural characteristic, one also have to take into consider food processing practices (Guillon&Champ2000).Assoonastheoriginfoodischanged,thepropertiesofDFcontent might be influenced. Heat treatment is a process that can break down glycoside bonds in polysaccharideswhichmightreducetheDFcontentorchangetheratiobetweenISFandSF. Withheatinginthepresenceofaminoacids,Millardreactionofpolysaccharidesisstarted whichproducenewpolymersthatlosethefibreproperties(Mongeau&Brooks2016).One ofthefirstthingsthatwasobservedwhentestinghowfoodprocessinginfluenceglycemic responsewasthatcookedfoodlikewheat,cornandpotatoesingestedsignificantlyhigher glucoseresponsethantheirrawcontributes(Bornetetal.1989).Fibreareinfluencedalsoby cutting,milling,cookingandboiling.Thegreateristhetransformationofgrains,vegetables andfruitsfromtheiroriginstructure,thelowerisintegrityofacellwall,lesslikelyitistohave beneficialeffectsonhealth(Guillon&Champ2000).However,changesthatcanbeobserved while food processing does not necessary correspond to what will be the change while digested.Whenfoodprocessincreasesolubilityandviscosityofameal,itdoesnotnecessary correspondtoincreaseviscosityinsmallintestinal.Sincethereisnoinvitromethodsthat would be able to show relationship between physicochemical properties of DF and their physiological effect, clinical studies have to be conducted to evaluate food processing influenceonhealthbenefitsoffibre(Guillon&Champ2000). 3.4. Dietaryfibrerecommendations Dietaryfibrearepresentineveryunprocessedfoodlikegrains,vegetables,fruits,nutsand seeds.Eventhoughtheycanbefoundinsuchbroadareaoffoodproducts,mostofthepeople failtoreachdailyrecommendations.Averagepersonfibreconsumptionhasbeendecreased duringlastdecadessincetheamountofprocessedDF-freefoodhasdramaticallyincreased (Mannetal.2015). USArecommendationsofdietaryfibretoreachadequateintakeare14g/1000kcalwhich correspondtoapproximately28g/dayforwomenand36g/dayformen(Usda&Dhhs2010). In1994USAreportedthat76%ofpeoplewhoeatbelow20goffibreperdayhaveself20 reportedthattheyareeatingsufficientamountoffibredaily(Alaimoetal.1994).Eventhough theawarenessofimportanceofdietaryfibrehasincreased,thefoodconsumedisreducedin fibrecontentanditreflectsintheaverageintakeoffibreonly15g/dayinUSA(Association 2008).It’ssurprisingthatmostofthefibreconsumedbyAmericanscomesfromwhiteflour and potatoes despite low DF values, since their consumption are the highest (Association 2008).InDenmarkandotherScandinaviancountriestherecommendationofDFintakeare 25-35g/daywhichcorrespondtoUSguidelines(NordicNutritionRecommendation2012).In 2008therewereonly6%ofDanesthatmeettheDFrecommendationseveryday,therefore the country started the campaign to raise the awareness of health benefits from eating enoughWGproductsandfibre.In5yearsafterthecampaignstarted,27%ofadultDanes and 43 % of children met the recommended amounts of whole grain food per day. The average consumption of whole grains have risen from 36 g/day to 63 g/day (75g/day recommended),respectively(DanishWholeGrainPartnership2014). 21 WHOLEGRAINSHEALTHEFFECTS MainrecommendationsareusuallyapproachingincreaseofWGconsumptioneventhough therearecontroversialresultsbetweenepidemiologicandclinicalstudieswhetherWGhave aneffectondiabetesparameters(Schulzeetal.2007;Jenkinsetal.1978).Ononehandmany epidemiologicstudiesshowthatWGandcerealsthatmainlyconsistofinsolublefibrehave the most prospect effect on risk of cardiovascular disease, incident of T2D and mortality (Schulzeetal.2007).Beneficialeffectsobservedincohortstudiesaremostpossiblearesult of many beneficial ingredients in WG and cannot be directly correlated only to higher DF intake(Babioetal.2010).InadditiontoISF,wholegrainsalsocontainpolyphenols,vitaminE andmagnesiumthatpossiblyinfluenceoverallhealthbeing(Counciln.d.).Cohortstudiesare duetomanycorrelationsthatmightinfluencetheresults,notabletoprovidereliablefactsto establishdefinitiveconclusions(Concatoetal.2000).However,theirresultsarestimulating researchgroupstoconstructrandomizecontroltrialstotestpredictedcorrelations. CohortstudiesincludedinreviewbyBabioetal,havesimultaneouslyshowndecreaseinrisk fordevelopingT2DassociatedwithhigherWGintake(Babioetal.2010).However,therewas no specification of grain and fibre types that could give us clear information of what has caused those results. One of the shown correlations from cohort studies was that cardiovascularincidentsaremoreconnectedtoelevatedpostprandialglycaemiathanfasting glucose,thereforemoreclinicalstudieswereconductedtotesttheeffectofcarbohydrate productsonglucoseresponseandevaluatetheirGI(Jenkinsetal.1987;TheDECODEstudy 1999;Brand-Milleretal.2003).ClinicalstudieswerenotabletoshowbeneficialeffectofWG onglycemicresponse,thereforeAmericanDiabetesAssociation(ADA)in1995concludedthat dietaryfibreprobablyhaveinsignificanteffectonglycemiccontrol(Complications2002).The inconsistencyofresultsisareflectionofdifferentdietaryfibrepropertiesthatwasfirstlynot taken into account. Studies of dietary fibre were in the beginning mainly focused on the question how much fibre is needed to have beneficial effect and secondly they have investigatewhattypeoffibreofferbetterphysiologicaleffects(Guillon&Champ2000).In clinicalstudies,ISFthatarethemaintypeoffibreinWGproducts,didnotperformdesirable effectonglycemicrespondandotherriskfactorsofdevelopingT2D(D.J.Jenkinsetal.2002). 22 VISCOUSSOLUBLEFIBRE In 1978 Jenkins et al. first compared different DF and their analogs to test the effect on glucosetoleranceandtoinvestigatecorrelationsbetweenfibrepropertiesandtheireffect (Jenkinsetal.1978).Outofsixdifferentfibreaddedtotheproducts,onlyguargumshowed significantreductioninpeakriseofglucoseconcentration.Theyshowedpositivecorrelation between increase viscosity of fibre added and greater reduction in peak rise and AUC. Increasedviscosityreflectsinslowerglucoseabsorptionandtransittimeandthereforeoffers effective way to decrease postprandial glycaemia. That was even further confirmed when they compare the effect of the same fibre with no viscous properties and showed that hydrolyzed guar gum did not perform any reduction of glucose response. The suggested mechanism is twofold, firstly viscous fibre delay gastric emptying and transit time and secondlyslowdownglucoseabsorptioninintestinal(Jenkinsetal.1978). Evenwhencomestoviscousfibre,notallofthemperformthesamephysiologicaleffect.In vitrostudiesshowedthatglycemicresponseofsolidfoodswithincorporatedVSFcorresponds tomolecularweightoffibreandtheirconcentrationthatinfluencedviscosity(Lan-Pidhainy etal.2007;Toshetal.2008).However,thesituationindigestivesystemmightbedifferent due to different physiological properties and environmental factors, therefore each fibre effectshavetobetestedindividually(Guillon&Champ2000). 1. Viscoussolublefibresupplementation EatingsufficientamountofSFisachallenge,sincetheyareonlypresentinbeans,lentils,chick peas, okra, barley, and oats. Moreover, it was shown that some of the natural occurring soluble fibre, like agar and pectin, do not have an effect on postprandial glycaemia even thoughtheymightdelayfooddigestion(Sanakaetal.2007).Forguargumitwasshownthat itmayloseitsactivityduetohydrolysisinstomachacidthatreflectsinreductionofviscosity (Regand et al. 2009). Moreover, even oats that are rich in viscous beta-glucans, show no differencesinGIcomparedtootherhighGIproducts(Granfeldtetal.1995).Therefore,many supplementsareavailableonthemarketthatcouldhelpinglycemiccontrol(Chutkanetal. 2012).Oneofthesupplementsthatjustrecentlyhavegottheapprovedhealthclaimfrom 23 Health Canada is a Polysaccharide Complex (PGX – PolyGlycompleX), containing glucomannan,xanthangumandsodiumalginate,thatwasusedinthestudyconductedfor thismasterthesis(USPatentNo:8,062,686)(Anonn.d.). 1.1. KonjacGlucomannan The main component of PGX is a glucomannan that is derivated from Konjac root (AmorphophallusKonjac)anditisasoluble,fermentableandhighlyvisousdietaryfibrethat haveabilitytoabsorbupto50timesitsweightwhendiluted(Keithley&Swanson2005;Davé &McCarthy1997). Picture1:AmorphophallusKonjacillustrationoffibreisolationsteps.Sourcewebpagewrapfataway.com–linkatPicture reference(1). 24 Picture2:AmorphophallusKonjacrootusedforglucomannanextraction;sourceWikipedia–sourcewebpagenaturdrogeriet.dk–linkatPicturereference(2). Konjacglucomannan(GM)has5timeshigherviscositythanguargumandbeta-glucansand itwasshowntobeoneofthefibrewiththehighestviscosity(Davé&McCarthy1997).In Japanisecultureithasbeenusedasfoodandremedyforaverylongtimeandtheywerealso thefirstonethatstartedtoinvestigatetheirpositiveoutcomesasadietaryfibre(M.etal. 1980). Konjacglucomannanwasshowntobebeneficialformanyhealthparameters.Vuksanetal. were the first to show its beneficial effect on high-risk diabetic patients when using it implementedintobiscuits.High-riskindividualswithT2Dgainedimprovementinmetabolic controlwhenGM-enrichedbiscuitswereaddedtoconventionaltreatment(drugtherapyand low-saturated fat diet)(Vuksan et al. 1999). Glucomannan has shown beneficial effect on glycemic control when used as a longer as well as shorter (acute) treatment. Its use also reflects in decrease of short-term marker of degree of diabetic control – fructosamine, howevertheyshownoeffectonfastingorinsulinsecretion.ItwassuggestedthatGMmay 25 potentiate the effect of drugs used for diabetes treatment. Furthermore, the same group continueswiththestudyandtestGM-enrichedbiscuitswithwheatbranfibrebiscuitstosee thedifferenceineffectofVSFcomparedtoinsoluble.Resultswereverysimilartoprevious research and supported better glycemic control for GM-group, significant reduction was observed in hyperglycemia and hyperlipidemia (Vuksan et al. 2000). Great reduction propertiesforloweringLDLcholesterolhavebeenshownandifcomparedtootherfibre,GM offerstriplelipid-reductioncomparedtopsyillum,oatproductandguargumaswellastwice thecapacityofpectins(Brownetal.1999;Vuksanetal.2000). 1.1.1. PolysaccharideComplex(PGX) PGXisaformulationofthreeviscousfibrethatactsynergisticallyandinduceseveraltimes higherviscositywhenusedtogether.Thisofferagreatpotentialtoachievethesamehealth resultsusingsmallerquantities.Sinceimplementingviscousfibreinfoodremainsachallenge duetotheirhighviscosity,implementingPGXmightbethesolutiontoobtainpalatabilityof products.ComparedtootherVSFlikeguargumthatreachesextremeviscosityimmediately whenmixedwithwater,PGXgelsslowerandreachesthehighestviscositywithdelaywhich isverybeneficialinfoodproduction(Brand-Milleretal.2010).A.L.Jenkinsetalshowedthat adding10gofVFBtobiscuitsresultsin74%ofGIreductioninhealthyparticipantsandin63 %GIreductionindiabeticpatientscomparedtowhitebreadcontrol,respectively(Jenkinset al.2008).Tocomparethiswithotherfibre,GlycemicReductionIndexPotencial(GRIP)that tells the degree of reduction per gram of added fibre, was calculated. GRIP values are therefore7.4whenusedinhealthypatientsand6.3fordiabeticpatients,whichisstronger reductionthanwasreportedofanyofothersolublefibre,evenGMalone(A.L.Jenkinsetal. 2002;Chearskuletal.2007;Sanakaetal.2007;Dahletal.2005). PGX is very potential fibre blend also because of its effect on weight loss (Onakpoya & Heneghan 2015). As mention before, T2D is very correlated to vascular fat and the first recommendationeverydiabeticpatientreceiveistoloseweight.Fibre-enrichedmealshave lowerenergydensesincethevolumeofthevolumeofthemealincreaseandreflectinhigher satiety.Moreover,theyaredigestedslowerandareabletoprolongthefeelingoffullness alsoduetotheeffectonhormonalhungersignalization(Kristensen&Jensen2011).Theeffect ismostpossiblethreefold,firstlyviscosityofamealincreasetransittimeandreflectsinslower 26 gastricempting(Dikeman&Fahey2006).Secondly,themetaboliceffectisobservedinslower absorptionofglucoseandothermacronutrientsthatreflectsinlowerpostprandialglucose elevation,andthirdly,endocrineeffectwasobservedinlowerproductionofhunger-related hormones like peptide YY, glucagon-like peptide-1 (GLP-1) and cholecystokinin (Wren & Bloom2007;Jenkinsetal.1978).Thesecharacteristicsarealltheeffectiveapproachestohelp inweightcontrol(Howarthetal.2009).StudyconductedbyVuksanetalcomparedviscous fibre blend preload (same properties as PGX) effects on food intake and conclude that significantlylowerintakewasobservedinVFBgroupcomparedtoinsolublecellulosefibre,as wellasGMitself(Vuksanetal.2009). 1.1.1.1. PGXhealthclaims In May 2016, Health Canada approved health claims for the use of PGX in food industry referringtoreducingofpostprandialglycaemiaandcholesterol.Inpostprandialglycaemia, they conclusion was based on six randomized control trial with cross-over design, that showedsignificantreductioninpostprandialglucoseiAUCin80%oftreatmentarms.The effectisachievedwhenaminimumof5gofPGXisaddedtoconsumemealdirectlyprior consumption.ThishealthclaimisnotallowedifPGXisaddedtoproductsthatrequireany kindoffoodprocessingpriorconsumption,sincethereisnoevidencetosupporttheeffect whenenrichedmealsarebaked,frozenorboiled(Anonn.d.).Incholesterolloweringeffect, fourstudiesshowedsignificantreductionintotalcholesterolfor75%oftreatmentarmsand inLDLcholesterollevelsforallarms.Theseresultsrequireaminimumof10gofPGXdailyfor atleast2weekswhenfibreareaddeddirectlypriorconsumption(Anonn.d.). 1.1.1.2. IncorporatingPGXintodifferentfoodmatrices AllthebeneficenteffectsofPGXwereshownwhendrypowderwassprinkledonthetopof foodmealsrightbeforeconsumption.However,askingpeopletosprinklesomethingonthe topofthefoodisnotthemostefficientwaytomakegeneralpopulationeatmoresoluble fibre.Therefore,RiskFactorModificationCenterinSt.MichaelHospitalinToronto,whereI didthepracticalworkforthismasterthesis,havegotthevisionofimplementingPGXinto commonlyconsumedrefinedcarbohydrateproductsduringprocessing.Refinedproductsare despiteawarenessoftheirlownutritionalvalue,stillthemostconsumedcarbohydratesin 27 Canada and USA (Association 2008). Whole grains are recommended by general health institutions,butduetolowerpalatability,noimprovementinamountoftheirconsumption havebeenachievedinlastdecades(Association2008).Apotentialwaytoimprovethiscould be to implement PGX into different refined carbohydrate products with retaining their palatability.SincePGXishighlyeffectiveinloweringpostprandialglycemia,loweramountcan beaddedtofinalproducts,whichmightbeapotentialwaytonotinfluencepalatability. 28 MYMASTERTHESISPROJECT MyworkinTorontostartedwithbakingandpreparingtestingsamplestoensureIwasable topreparethesameproductsthathavebeendonebefore.Beforemyarrivaltheyalready conductedthephaseIofthestudy,sotheyalreadyknewthattheimplementationofPGXin productdidnotinfluencepalatabilityinmostofthecases. Picture3:Theexampleofbakedproductusedinthestudypriordividingintosample;picturetakenbyTajaKarner. Afteralltheproductswerebaked,preparedandsampledwerecruithealthyindividualsto participateinthestudy.RecruitmentroomisshownonPicture2. 29 Picture4:RecruitmentroominRiskFactorModificationCenter(RFMC)inSt.MichaelHospital,Toronto,Canada;picture takenbyTajaKarner. . Picture5:LaboratoryinRFMCwherebloodsampleswereanalyzed;picturetakenbyTajaKarner.. Onthepicture3isthelabweusedforanalysisbloodsamples.Afterwefinishwithparticipants and sample analysis, I focused on analysis of results and compared them to what has previouslybeenestablished.Ilearnedalotabouttheprotocoloftheclinicaltrails,which 30 thingshavetobetakeninaccount,whatcangowrongandhowtopreventit.Mostofallit wasanexcellentexperiencethatwillhelpmetounderstandotherclinicaltrialsmoresinceI wasonceapartofone. The results of our study showed beneficial effects in lowering postprandial peak values in glucoserise,howevernoeffectwasobservedinglucoseiAUC.Interestingobservationfrom theindividualmealresponsesisthatbothcreamofwheatandmashedpotato(non-baked) treatments displayed a slightly more prominent glucose lowering response compared to whitebreadandmuffintreatments(bakedproducts).Itisverylikelythatun-sufficientability toreachfibre’shighestviscositymaskeditspositiveeffectonpostprandialglycaemia.Even thoughthereweresignificantresultsinmanyaspectsinoveralltreatmentproductscompared tooverallcontrol,productsindividuallylacksignificanceanddidnotperformasdesirable.For detailedresultsrefertothepaper:“VladimirVuksan,TajaKarner,AmandaMa,ElenaJovanovski, FeiAuYeung:EffectofPalatableSolubleFibre-ContainingCarbohydrateFoodsonPostprandialBlood Glucose Response in Healthy Individuals: A Randomized, Controlled, Double-blinded Study” (not publishedyet). 31 CONCLUSION Consumption of highly viscous fibre was shown to successfully lower postprandial blood glucoseandofferpotentialwaytoaddresshighglycemicresponsesrelatedtoincreaseriskof developingT2D.IncorporationofVSFintocommonlyconsumedCHOproductshasapotential to reduce GI of highly processed food. Since VSF incorporation reflect in lower products’ palatability, fibre blends like PGX with fibre combination that acts synergistically and can perform the same health effects when used in smaller dosage, might offer a solution to developpalatablefibre-enrichedproducts. Intheperformedstudywewereabletoobtainpalatabilityof3outof4products.However, nosignificanteffectwasshowninglucoseiAUCbetweenfibre-enrichedandcontrolsamples. SincehealthyclaimregardedPGXrefertotheuseoffibreblendsprinkledonthefoodright before consumption, cooking and baking process in our study might influenced overall potential. Moreover, it was concluded that 5 g of PGX are necessary to perform desirable physiologicaleffect.However,inthestudyperformed,only4gwasimplementedintofood products.Eventhoughthesuccessofimplementingisnotprovenefficientlyyet,weshould nottakethisopportunityforgrantedandmorefacilitiesandcompaniesshouldworktogether andfindthebestsolutionhowtoincorporatethisorsimilarhighlyviscousblendsintovariety of products. Eating higher amount of fibre and still enjoying hedonic appearance of refined productcouldbeapotentialwaytoimproveoverallhealth,decreasediabetesratesandimprove people’sdiets.However,theproposeofthisimprovementisnottosupportpeopletoeatmore refinedproducts,thereforeclearstatementshouldbemadetoclarifythatthisisstillnotahealthy mealduetolownutritionalvalue. Clear and non-misleading marketing should be a priority whenputonamarket. 32 PERSPECTIVE FurtherdevelopmentofproductswherePGXcouldreachitsmaximumviscosityproperties shouldbeconsidered.PGXcouldbeaddedtovariousdifferentproducts,basedonthemost consumedrefinedproductinspecificcountry.AddingPGXtocerealsandwhitebread,which aremosttraditionalbreakfastfoods,isapotentialwaytohelpconsumersnottoriseglucose leveltoohighfirstthinginthemorning.ThatmightlowertheriskofdevelopingT2D,since insulinsensitivityisatitslowestpointafterovernightfasting,possiblyduetoelevationofFFA duringthenight(D.J.Jenkinsetal.1987).Itwouldalsobeinterestingtolookintosecond mealeffect,sinceitwasshownthatmetabolicresponseofamealmayinfluencenextmeals inaday.Ifweprovidebreakfastproductswithincreaselevelofviscoussolublefibre,itmay flattertheresponseofthenextmeal,evenifrefinedanddonotcontainanyfiber(Jenkinset al.1982;Brand-Milleretal.2010) Long-termstudytoevaluatetheeffectofeverydayconsumptionofdevelopedproductsin diabetic patients could be considered and evaluation of its effect on hyperglycemia and hyperlipidemiacanbeaninterestedaspecttoseehowitcanbenefitpatientswithdiabetes. 33 BIBLIOGRAPHY Ahmad,O.B.,Boschi-pinto,C.&Lopez,A.D.,2001.Agestandardizationofrates:anewWHO standard,Availableat:http://www.who.int/healthinfo/paper31.pdf. Alaimo,K.,McDowell,M.&Briefel,R.,1994.Dietaryintakeofvitamins,minerals,andfiberof personsages2monthsandoverintheUnitedStates:ThirdNationalHealthandNutrition ExaminationSurvey.AdvancedData,(258),pp.1–28. Anon,SummaryofHealthCanada’sassessmentofahealthclaimaboutapolysaccharidecomplex (glucomannan,xanthangum,sodiumalginate)andareductionofthepost-prandialblood glucoseresponse.,(May2016),pp.1–6.Availableat:http://www.hc-sc.gc.ca/fn-an/labeletiquet/claims-reclam/assess-evalu/glucose-complex-polysaccharides-complexe-glycemiqueeng.php.Accessed:30thofMay2016. Ashwell,M.,Gunn,P.&Gibson,S.,2012.Waist-to-heightratioisabetterscreeningtoolthanwaist circumferenceandBMIforadultcardiometabolicriskfactors:Systematicreviewandmetaanalysis.ObesityReviews,13(3),pp.275–286. Association,A.D.,2008.PositionoftheAmericanDieteticAssociation:HealthImplicationsofDietary Fiber.JournaloftheAmericanDieteticAssociation,108(10),pp.1716–1731.Availableat: http://www.sciencedirect.com/science/article/pii/S0002822308015666.Accessed:30thofMay 2016. Babio,N.etal.,2010.Dietaryfibre:Influenceonbodyweight,glycemiccontrolandplasma cholesterolprofile.NutricionHospitalaria,25(3),pp.327–340. Bornet,F.R.J.etal.,1989.Insulinandglycemicresponsesinhealthyhumanstonativestarches processedindifferentways:Correlationwithinvitroα-amylasehydrolysis.AmericanJournalof ClinicalNutrition,50(2),pp.315–323. Brand-Miller;Hayne,Petocz,C.,2003.Low-glycemicindexdietsinthemanagementofdiabetes:a meta-analysisofrandomizedcontrolledtrials.ClinicalCare/Education/Nutrition,26(8), pp.2261–7. Brand-Miller,J.C.etal.,2010.EffectsofPGX,anovelfunctionalfibre,onacuteanddelayed postprandialglycaemia.Europeanjournalofclinicalnutrition,64(12),pp.1488–93. Brown,L.etal.,1999.Cholesterol-loweringeffectsofdietaryfiber:Ameta-analysis.American JournalofClinicalNutrition,69(1),pp.30–42. Buchanan,T.A.&Xiang,A.H.,2005.Gestationaldiabetesmellitus.TheJournalofclinical investigation,115(3),pp.485–91.Availableat:http://www.jci.org/articles/view/24531. Burton,P.M.etal.,2011.Glycemicimpactandhealth:newhorizonsinwhitebreadformulations. 34 Criticalreviewsinfoodscienceandnutrition,51(10),pp.965–82. Cabrera,O.etal.,2006.Theuniquecytoarchitectureofhumanpancreaticisletshasimplicationsfor isletcellfunction.ProceedingsoftheNationalAcademyofSciencesoftheUnitedStatesof America,103(7),pp.2334–9. Carr,D.B.etal.,2004.Intra-abdominalfatisamajordeterminantoftheNationalCholesterol EducationProgramAdultTreatmentPanelIIIcriteriaforthemetabolicsyndrome.Diabetes, 53(8),pp.2087–2094. Chearskul,S.etal.,2007.GlycemicandlipidresponsestoglucomannaninThaiswithtype2diabetes mellitus.JournaloftheMedicalAssociationofThailand,90(10),pp.2150–2157. Choi,K.&Kim,Y.-B.,2010.Molecularmechanismofinsulinresistanceinobesityandtype2diabetes. TheKoreanjournalofinternalmedicine,25(2),pp.119–29. Chutkan,R.etal.,2012.Viscousversusnonviscoussolublefibersupplements:Mechanismsand evidenceforfiber-specifichealthbenefits.JournaloftheAmericanAcademyofNurse Practitioners,24(8),pp.476–487. Complications,A.D.A.T.F.forW.N.P.andR.fortheM.ofD.andR.,2002.AmericanDiabetes Associationpositionstatement:evidence-basednutritionprinciplesandrecommendationsfor thetreatmentandpreventionofdiabetesandrelatedcomplications.JournaloftheAmerican DieteticAssociation,102(1),pp.109–118.Availableat: http://ovidsp.ovid.com/ovidweb.cgi?T=JS&PAGE=reference&D=med4&NEWS=N&AN=1179449 0.Accessed:30thofMay2016. Concato,J.,Shah,N.&Horwitz,R.I.,2000.Randomized,controlledtrials,observationalstudies,and thehierarchyofresearchdesigns.TheNewEnglandjournalofmedicine,342(25),pp.1887–92. Council,W.G.,SummaryofRecentResearchOnWholeGrainsandHealth.WholeGrainsCounciland Oldways.Availableat:www.WholeGrainsCouncil.org.Accessed:30thofMay2016. Dabelea,D.,2009.Theacceleratingepidemicofchildhooddiabetes.TheLancet,373(9680), pp.1999–2000. Dahl,W.J.etal.,2005.Effectsofflaxfiberonlaxationandglycemicresponseinhealthyvolunteers. Journalofmedicinalfood,8(4),pp.508–11.Availableat: DanishWholeGrainPartnership,2014.WholegrainintakesetsnewrecordFactsabouttheFood Institute’sdietarysurvey.,pp.1–3. Davé,V.&McCarthy,S.,1997.Reviewofkonjacglucomannan.JournalofPolymersandthe Environment,5(4),pp.237–241.Availableat:http://dx.doi.org/10.1007/BF02763667. DEFRONZO,R.A.,1988.Thetriumvirate:β-cell,muscle,liver.AcollusionresponsibleforNIDDM. Diabetes,37(6),pp.667–687. 35 Dikeman,C.L.&Fahey,G.C.,2006.Viscosityasrelatedtodietaryfiber:areview.Criticalreviewsin foodscienceandnutrition,46(8),pp.649–663. Drouin,P.etal.,2009.Diagnosisandclassificationofdiabetesmellitus.DiabetesCare, 32(Supplement_1),pp.S62–S67. Exton,J.H.,1972.Gluconeogenesis.Metabolism,21(10),pp.945–990. Ezzati,M.,2016.Worldwidetrendsindiabetessince1980:Apooledanalysisof751populationbasedstudieswith4??4millionparticipants.TheLancet,387(10027),pp.1513–1530. Flamm,G.etal.,2001.Inulinandoligofructoseasdietaryfiber:areviewoftheevidence.Critical reviewsinfoodscienceandnutrition,41(5),pp.353–362. Fonseca,V.A.,2009.Definingandcharacterizingtheprogressionoftype2diabetes.Diabetescare, 32Suppl2. Fourlanos,S.etal.,2005.Latentautoimmunediabetesinadults(LADA)shouldbelesslatent. Diabetologia,48(11),pp.2206–2212. Frontoni,S.etal.,2013.Glucosevariability:Anemergingtargetforthetreatmentofdiabetes mellitus.DiabetesResearchandClinicalPractice,102(2),pp.86–95. Gao,Z.etal.,2002.Serinephosphorylationofinsulinreceptorsubstrate1byinhibitorkappaB kinasecomplex.TheJournalofBiologicalChemistry,277(50),pp.48115–48121. Granfeldt,Y.,Hagander,B.&Björck,I.,1995.Metabolicresponsestostarchinoatandwheat products.Ontheimportanceoffoodstructure,incompletegelatinizationorpresenceof viscousdietaryfibre.Europeanjournalofclinicalnutrition,49(3),pp.189–199. Guillon,F.&Champ,M.,2000.Structuralandphysicalpropertiesofdietaryfibres,and consequencesofprocessingonhumanphysiology.FoodResearchInternational,33(3-4), pp.233–245. Henquin,J.C.,2004.Pathwaysin ??-cellstimulus-secretioncouplingastargetsfortherapeuticinsulin secretagogues.InDiabetes. Howarth,N.C.,Saltzman,E.&Roberts,S.B.,2009.DietaryFiberandWeightRegulation.Nutrition Reviews,59(5),pp.129–139. Jenkins,aL.etal.,2002.Depressionoftheglycemicindexbyhighlevelsofbeta-glucanfiberintwo functionalfoodstestedintype2diabetes.Europeanjournalofclinicalnutrition,56(7),pp.622– 628. Jenkins,A.L.etal.,2008.Comparablepostprandialglucosereductionswithviscousfiberblend enrichedbiscuitsinhealthysubjectsandpatientswithdiabetesmellitus:acuterandomized controlledclinicaltrial.Croatianmedicaljournal,49(6),pp.772–82. 36 Jenkins,D.J.etal.,1978.Dietaryfibres,fibreanalogues,andglucosetolerance:importanceof viscosity.Britishmedicaljournal,1(6124),pp.1392–4. Jenkins,D.J.etal.,1987.Starchyfoodsandfiber:reducedrateofdigestionandimproved carbohydratemetabolism.Scandinavianjournalofgastroenterology.Supplement,129,pp.132– 41. Jenkins,D.J.aetal.,2002.Effectofwheatbranonglycemiccontrolandriskfactorsfor cardiovasculardiseaseintype2diabetes.Diabetescare,25(9),pp.1522–1528. Jenkins,D.J.A.etal.,1987.Metaboliceffectsoflow-glycemic-indexdiet.AmericanJournalofClinical Nutrition,46(6),pp.968–975. Jenkins,D.J.A.,Wolever,T.M.S.&Taylor,R.H.,1981.Glycemicindexoffoods:Aphysiologicalbasis forcarbohydrateexchange.AmericanJournalofClinicalNutrition,34(3),pp.362–366. Jenkins,J.aetal.,1982.Slowreleasesecondmealdietarycarbohydrateimproves.,pp.1339–1346. Jensen,H.,Agger,A.O.&Rasmussen,K.L.,1999.Theinfluenceofprepregnancybodymassindexon laborcomplications.ActaObstetriciaEtGynecologicaScandinavica,78(9),pp.799–802. John,L.&Jeffery,A.,2000.BeneficialeffectsofviscousdietaryfiberfromKonjac-mannanin... Jones,J.M.,2014.CODEX-aligneddietaryfiberdefinitionshelptobridgethe“fibergap”.Nutrition journal,13(1),p.34. Kahn,S.E.,2003.Therelativecontributionsofinsulinresistanceandbeta-celldysfunctiontothe pathophysiologyofType2diabetes.Diabetologia,46(1),pp.3–19. Kahn,S.E.,Hull,R.L.&Utzschneider,K.M.,2006.Mechanismslinkingobesitytoinsulinresistance andtype2diabetes.Nature,444(7121),pp.840–846. Keithley,J.&Swanson,B.,2005.Glucomannanandobesity:Acriticalreview.AlternativeTherapies inHealthandMedicine,11(6),pp.30–34. Kristensen,M.&Jensen,M.G.,2011.Dietaryfibresintheregulationofappetiteandfoodintake. Importanceofviscosity.Appetite,56(1),pp.65–70.Availableat: http://dx.doi.org/10.1016/j.appet.2010.11.147. Lam,D.W.&LeRoith,D.,2012.Theworldwidediabetesepidemic.Currentopinioninendocrinology, diabetes,andobesity,19(2),pp.93–6. Lan-Pidhainy,X.etal.,2007.Reducingbeta-glucansolubilityinoatbranmuffinsbyfreeze-thaw treatmentattenuatesitshypoglycemiceffect.CerealChemistry,84(5),pp.512–517. Langer,O.etal.,2005.Gestationaldiabetes:Theconsequencesofnottreating.InAmericanJournal ofObstetricsandGynecology.pp.989–997. 37 Lattimer,J.M.&Haub,M.D.,2010.Effectsofdietaryfiberanditscomponentsonmetabolichealth. Nutrients,2(12),pp.1266–1289. M.,M.,Y.,H.&A.,K.,1980.Treatmentofdiabeteswithglucomannan.JournaloftheJapanDiabetes Society,23(3),pp.209–217. Mann,J.etal.,2007.FAO/WHOscientificupdateoncarbohydratesinhumannutrition:conclusions. Europeanjournalofclinicalnutrition,61Suppl1,pp.S132–S137. Mann,K.D.etal.,2015.Wholegrainintakeanditsassociationwithintakesofotherfoods,nutrients andmarkersofhealthintheNationalDietandNutritionSurveyrollingprogramme2008-11. TheBritishjournalofnutrition,113(10),pp.1595–602. Mokdad,A.H.etal.,2003.Prevalenceofobesity,diabetes,andobesity-relatedhealthriskfactors, 2001.JAMA :thejournaloftheAmericanMedicalAssociation,289(1),pp.76–9. Mongeau,R.&Brooks,S.P.J.,2016.DietaryFiber:PropertiesandSources☆1sted.,ElsevierLtd. Availableat:http://linkinghub.elsevier.com/retrieve/pii/B9780123849472007844.Accessed: 30thofMay2016. Montague,C.T.&O’Rahilly,S.,2000.Theperilsofportliness:Causesandconsequencesofvisceral adiposity.Diabetes,49(6),pp.883–888. Onakpoya,I.J.&Heneghan,C.J.,2015.Effectofthenovelfunctionalfibre,polyglycoplex(PGX),on bodyweightandmetabolicparameters:Asystematicreviewofrandomizedclinicaltrials. CLINICALNUTRITION,34(6),pp.1109–1114. Otles,S.&Ozgoz,S.,2014.Healtheffectsofdietaryfiber.Actascientiarumpolonorum.Technologia alimentaria,13(2),pp.191–202. Reaven,G.M.,1988.Roleofinsulinresistanceinhumandisease.Diabetes,37(12),pp.1595–1607. Regand,A.etal.,2009.Physicochemicalpropertiesofbeta-glucanindifferentlyprocessedoatfoods influenceglycemicresponse.Journalofagriculturalandfoodchemistry,57(19),pp.8831–8838. Saini,V.,2010.Molecularmechanismsofinsulinresistanceintype2diabetesmellitus.Worldjournal ofdiabetes,1(3),pp.68–75. Saltiel,A.R.&Kahn,C.R.,2001.Insulinsignallingandtheregulationofglucoseandlipidmetabolism. Nature,414(6865),pp.799–806. Samuel,V.T.,Petersen,K.F.&Shulman,G.I.,2010.Lipid-inducedinsulinresistance:unravellingthe mechanism.TheLancet,375(9733),pp.2267–2277. Sanaka,M.etal.,2007.Effectsofagarandpectinongastricemptyingandpost-prandialglycaemic profilesinhealthyhumanvolunteers.ClinicalandExperimentalPharmacologyandPhysiology, 34(11),pp.1151–1155. 38 Scheen,A.J.,2003.Pathophysiologyoftype2diabetes.ActaClinicaBelgica,58(6),pp.335–341. Schneeman,B.O.,1998.Dietaryfiberandgastrointestinalfunction.NutritionResearch,18(4), pp.625–632. Schulze,M.B.etal.,2007.Fiberandmagnesiumintakeandincidenceoftype2diabetes:a prospectivestudyandmeta-analysis.ArchInternMed,167(9),pp.956–965. Shaw,J.E.,Sicree,R.A.&Zimmet,P.Z.,2010.Globalestimatesoftheprevalenceofdiabetesfor2010 and2030.DiabetesResearchandClinicalPractice,87(1),pp.4–14. Shaw,J.E.,Sicree,R.A.&Zimmet,P.Z.,2010.Globalestimatesoftheprevalenceofdiabetesfor2010 and2030.DiabetesResearchandClinicalPractice,87(1),pp.4–14. Shulman,G.I.,2004.Unravelingthecellularmechanismofinsulinresistanceinhumans:newinsights frommagneticresonancespectroscopy.Physiology(Bethesda,Md.),19,pp.183–190. Singh,G.M.etal.,2013.TheAge-SpecificQuantitativeEffectsofMetabolicRiskFactorson CardiovascularDiseasesandDiabetes:APooledAnalysis.PLoSONE,8(7). TheDECODEstudygroup,1999.Glucosetoleranceandmortality:comparisonofWHOandAmerican DiabeticAssociationdiagnosticcriteria.TheLancet,354(9179),pp.617–621. TheExpertCommitteeontheDiagnosisandClassificationofDiabetesMellitus,2003.Reportofthe ExpertCommitteeontheDiagnosisandClassificationofDiabetesMellitus.Diabetes,26(suppl 1),pp.5–20. Tosh,S.M.etal.,2008.Glycemicresponsetooatbranmuffinstreatedtovarymolecularweight of ??-glucan.CerealChemistry,85(2),pp.211–217. Usda&Dhhs,2010.DietaryGuidelinesforAmericans,2010.7ThEdition,p.76. Vuksan,V.etal.,1999.Konjac-mannan(glucomannan)improvesglycemiaandotherassociatedrisk factorsforcoronaryheartdiseaseintype2diabetes.Arandomizedcontrolledmetabolictrial. Diabetescare,22(6),pp.913–919. Vuksan,V.etal.,2009.Viscosityoffiberpreloadsaffectsfoodintakeinadolescents.Nutrition, MetabolismandCardiovascularDiseases,19(7),pp.498–503. Wanders,A.J.etal.,2014.Pectinisnotpectin:Arandomizedtrialontheeffectofdifferent physicochemicalpropertiesofdietaryfiberonappetiteandenergyintake.Physiologyand Behavior,128,pp.212–219. WHO,2003.Diet,nutritionandthepreventionofchronicdiseases.WorldHealthOrganization technicalreportseries,916,pp.i–viii–1–149–backcover.Availableat: http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=12768890&retmod e=ref&cmd=prlinks\npapers3://publication/uuid/734F6B31-260B-4545-A8E4-57F7D35DDEB8. Accessed:30thofMay2016. 39 Wong,J.M.W.&Jenkins,D.J.a,2007.Carbohydratedigestibilityandmetaboliceffects.TheJournal ofnutrition,137(11Suppl),p.2539S–2546S. WorldHealthOrganization,2016.GlobalReportonDiabetes.,p.6.Availableat: http://apps.who.int/iris/bitstream/10665/204871/1/9789241565257_eng.pdf.Accessed:30th ofMay2016. Wren,A.M.&Bloom,S.R.,2007.GutHormonesandAppetiteControl.Gastroenterology,132(6), pp.2116–2130. Zierler,K.,1999.Wholebodyglucosemetabolism.AmericanJournalofPhysiology-Endocrinology andMetabolism,276(3),pp.E409–E426. Picture4and5reference: 1.Accessedfromwrapfataway.com,30thofMay,2016. http://wrapfataway.com/wp-content/uploads/2015/07/Glucomannan-Supplement.png 2.Accessedfromnatur-drogeriet.dk,30thofMay,2016.Sameascoverphoto. http://www.naturdrogeriet.dk/frame.cfm/cms/produktblad=yes/npv=22648/npbv=22648/sprog=1/grp=101/menu=10 1 40