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EvaluatingtheEfficacyofDiaMetrix™inaRandomized,Double‐Blind
PlaceboControlledHumanClinicalTrial
KennethR.Hampshire1,StevenMiles1,RickMiles1,RobertT.Streeper2,JoelMichalek3,
ChristopherLouden3,ElzbietaIzbicka2&
1Syntratech™Corporation,Denver,Colorado,Colorado,USA,80237,800‐738‐0650,
www.syntratech.com,
2CPCLTD,SanAntonio,Texas,USA
3UniversityofTexasHealthScienceCenteratSanAntonio,SanAntonio,Texas,USA
&correspondingauthor
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ABSTRACT
Background:Peoplewithdiabetesareathighriskofcardiaccomplications,whichare
exacerbatedbyelevatedbloodpressureanddysfunctionalsugarandfatmetabolism.
Theaimofthisstudywastoevaluateeffectsofanherbalsupplement,DiaMetrix,on
bloodglucoselevels,triglycerides,cholesterol,andbloodpressureinsubjectswith
chronicuncontrolledbloodglucose.
Methods:Wedidarandomizedprospectivedouble‐blindedstudyin100subjects(47
menand53women)withfastingbloodglucoselevelsbetween160and240mg/dL.The
participantswererandomlyassignedtooralDiaMetrixat6tabletsdaily(n=50)or
placebo(n=50)for90days.Theendpointsincludedfastingbloodglucose,bodymass,
oralglucosetolerancetest,totalcholesterol,HDL,triglycerides,glycosylated
hemoglobinandbloodpressure.
Results:Allstudyparticipantscompletedthestudy.DiaMetrixreducedHbA1c,blood
glucose(fastingandafterchallenge),triglycerides,systolicanddiastolicbloodpressure,
totalcholesterol,andbodymassovertime.Meanfastingglucosewassignificantly
decreasedinsubjectstakingDiaMetrixat30,60and90daysafterbaselinerelativeto
thosetakingplacebo.HbA1cmeanchangefrombaselineto90dayswassignificantly
decreasedinsubjectstakingDiaMetrix.TheDiaMetrixmeanserumglucosewas
significantlydecreasedrelativetoplaceboat30,120and180minutesafterthe
challenge.Triglyceridesmeanchangesfrombaselineweresignificantlydecreasedby
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DiaMetrixat30,60and90days.Fortotalcholesterol,DiaMetrixmeanchangefrom
baselineto90dayswassignificantlydecreasedrelativetoplacebo.Highandlow
densitylipoproteinswerenotsignificantlyaffected.Systolicanddiastolicblood
pressurewassignificantlydecreasedat60‐90days,andmeanbodymasswas
significantlydecreasedrelativetoplaceboat90days.
Conclusions:Thisstudydemonstratedareductioninthemeanfastingbloodsugar,
bloodpressureandbodymassinsubjectsrandomizedtoDiaMetrix.Thesefindingsof
suggestthatDiaMetrix,anover‐thecounterpreparation,deservesfurtherevaluationof
itsactivityinlargerclinicalstudies.
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Introduction
Basedonthedatafromthe2007NationalDiabetesFactSheetpublishedbythe
AmericanDiabetesAssociation,23.6millionchildrenandadultsintheUnitedStates
(7.8%ofthepopulation)havediabetesand1.6millionnewcasesofdiabetesare
diagnosedinpeopleaged20yearsandoldereachyear(1).In2003‐2004,therewerean
estimated5.7millionpeoplewithundiagnoseddiabetesand57millioninapre‐diabetes
stateintheUnitedStates(2).Inthelatter,bloodglucoselevelsknownasimpaired
fastingglucose(IFG)orimpairedglucosetolerance(IGT)areintherangeof100‐125
mg/dL,whilehigherlevelsareassociatedtype2diabetesmellitus,nowincreasingly
recognizedasanautoimmune‐inflammatorydisease(2).Notably,peoplewithpre‐
diabetesareatincreasedriskofdevelopingtype2diabetes,aconditioncharacterized
byimpairedinsulinsecretionfrompancreaticLangerhansislandscells,increasedhepatic
glucoseproductionandinconsequencehighbloodglucoselevels,anddecreaseduseof
glucoseinmuscletissue.Thesedefectsaremainlyresponsibleforthedevelopmentand
progressionoftype2diabetes(3).Furthermore,insulinresistanceisassociatedwith
decreasedratesofglycolysis,glycogenesis,lipogenesis,andproteinsynthesis.People
withtype2diabetesarealsoathighriskoffatalandnon‐fatalvascularevents.In
2003–2004,75%ofadultswithself‐reporteddiabeteshadelevatedbloodpressureof>
130/80mmHgorusedprescriptionmedicationsforhypertension.Intensivecontrolof
glycemiadecreasessomevascularcomplicationssuchasretinopathyandnephropathy
(4).
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DiaMetrix™isanherbaldietarysupplementcomposedofvitaminC(ascorbicacid),
biotinUSP,chromium(chelate),vanadium(chelate),garciniacambogiaextract(50%
hydroxycitricacid),gymnemasylvestreextract(25%),cinnamonextract(4:1),bitter
melonextract(10:1),betaineHCL,banabaextract(1%corosolicacid),fennugreek,
dicalciumphosphate,cellulose,croscarmellosesodium,stearicacid,silicondioxide,
magnesiumstearate,andhydroxypropylmethylcellulose.
AnotherrecentlycompletedstudycomparedtheactivityofDiaMetrixtothatofthree
anti‐diabeticdrugs;Metformin,Actos(pioglitazonehydrochloride),andByetta
(exenatide)inanobesediabeticmousemodelusingBKS.Cg‐m+/+Leprdb/BomTacfemale
micefedeithernormaldietorhighfatdiet(HFD)+/‐drugs.DiaMetrix’sprotection
againstorgandamagewascomparabletothatofByettaandbetterthanActosand
Metforminintheanimalsonnormaldiet.Themeanvaluesofmostinflammatory
plasmabiomarkerswereelevatedinhighfatdietrelativetonormaldiet.Biomarker
meansvariedsignificantlybytreatmentgroupanddiet.Onnormaldiet,DiaMetrix
decreasedlevelsofanumberofpro‐inflammatorycytokines,chemokinesandgrowth
factorssuchaseotaxin,MCP‐1,MCP‐3,M‐CSF,andincreasedanti‐inflammatory
cytokineIL‐4relativetountreated.DiaMetrixtreatmentdecreasedG‐CSF,GM‐CSF,and
TGFβrelativetountreatedinhighfatanimals.PyruvatekinaseandAGEincreased,
whileinsulinwasdecreasedinanimalstreatedwithDiaMetrixrelativetountreatedon
normaldiet.DiaMetrixdemonstratedsuperioranti‐inflammatoryactivityrelativetothe
commonlyusedanti‐diabeticdrugsagainstabackgroundofgeneticobesity,supporting
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thecontentionthatDiaMetrixmaybeaneffectiveinterventionfortype‐2diabetes
(Hampshireetal.,submitted).
ThegoalofthisclinicalstudywastoassesstheefficacyofDiaMetrixtreatmentin
diabeticsubjectswithfastingbloodglucoselevelsbetween160and240mg/dLandto
evaluateeffectsoforalDiaMetrixonclinicalendpointsusedintheroutineevaluationof
diabeticsubjects.Safetydatawasnotcollected.
METHODS
Subjects
SyntraTechcontractedtheclinicalstudywithacontractresearchorganization,Fenestra
ResearchLaboratories(Fenestra),LasVegas,NV.Fenestraalsoconductedthetestsas
describedbelow.In2006‐2007,Fenestrarecruited47menand53womenages23to50
(33Black,32Caucasian,25Asianand10Hispanic)usingparticipantsrecruitedfroma
largediversepopulationofpeoplelivinginorneartheLasVegas,NVarea,withchronic
uncontrolledbloodglucose(peoplewithfastingbloodglucoselevelsbetween160
mg/dLand240mg/dLwithameanof197mg/dL).
Excludedweresubjectswithahistoryofheadtrauma,seriousdiseasesorillness
diagnosedatthistime,knownmoderatetosevererenalinsufficiency,recenthistory(<6
monthspriortoVisit1)ofmyocardialinfarction.Alsoexcludedwerethosewho
regularlyusedoxygentherapy,thosewithknownactivetuberculosis,withtreatedbasal
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cellcarcinoma,historyofcancerwithinthelast5years,thoracotomywithpulmonary
resectionwithin1yearpriortothetrial,thoseinapulmonaryrehabilitationprogramor
whocompletedapulmonaryrehabilitationprograminthe6weekspriortothe
screeningvisit(Visit1),takingprescribeddiureticmedications,cardiacstimulants,or
anyotherprescribedornon‐prescribedmedicationthatmightaltertestingresults,
thosetakingopiateanalgesicsprescribedorotherwiseobtainedforanytreatment
reasonincludingmigrainetreatment,orforrecreationandhistoryofdrugaddictionor
alcoholaddictionwithinsix(5)monthsofthisstudyperiod,femaleswhowerepregnant,
lactating,ornursingorwhomaybecomepregnantduringthecourseofthestudy,and
thosediagnosedasHIV‐positive,diagnosedwithAIDS,orwithanyneuromuscular
conditionincludingCP,MS,ALS,orHuntington'sChorea.Alsoexcludedwerepeople
withuncontrolledhypertension(e.g.BP>140/90),oranyconditionnotpreviously
namedthat,intheopinionofFenestrainvestigatorsorintakestaff,wouldjeopardize
safetyoraffectthevalidityoftheresultscollectedinthisstudy.
Thestudyincludedfemalesormales18yearsofageorolder,whosignedawritten
informedconsent.Tobeeligibleforinclusion,potentialsubjectswererequiredto
documentbloodsugarimbalanceforaminimumofthepreviousconsecutive6months
ofthescreeningvisitatafrequencyofatleasttwenty(20)timeseachmonthbasedon
dailyglucometerreadings.Eligibleparticipantswererandomizedintotwogroupsof50
participants.Thestudywasdoubleblinded.
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Compliancetoinclusionandexclusioncriteriawasmonitoredandmaintainedthrough
bi‐weeklyphonecallswithFenestrapersonnelandin‐personofficevisits.All
participantswereinstructedtocontacttheirregularhealthcareprofessionaliftheyhad
anyunusualoruncomfortablesymptomsduringthecourseofthisstudy.All
participantswereinstructedtomakenochangestotheirdailyactivityorconsumption
offoodorliquidrelatingtotheamount,volume,ortypeconsumed.
Procedures
Participantsinbothtreatmentgroups,DiaMetrixandplacebo(vegetariantablet,
magnesiumcitrate,silicondioxide),wereinstructedtotaketwotabletsthreetimes
daily,orthreetabletstwotimesdailyifonlytwomeals,approximately15minutes
beforemeals.Participantswereinstructedtotakeproductonlyiftheyateameal.
Participantswhometallinclusioncriteriaandnoneoftheexclusioncriteriaatthefirst
visit(day0)andgavesignedinformedconsentwerethenprovidedeithertheplaceboor
DiaMetrix™alongwithinstructionsdescribingdailydosingtofollowforthedurationof
thestudy.Baselinemeasurementsweremadeatday1(visit2).Followingscreening
(day0),randomization,andsignedinformedconsent,participantsentereda1‐week
baselineperiod.Inthattime,participantswereaskedtorefrainfromtakingany
unnecessaryover‐the‐counterorprescriptionmedications,ornaturalproductsthatthey
werenotalreadytakingfortheremainderofthestudy.Ibuprofen,acetaminophen,and
aspirinwereallowed.Atthethirdandfourthvisits(days14and30)evaluationswere
performedfollowingstandardproceduresandtheinclusionandexclusioncriteriawere
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againreviewedwitheachparticipantonanindividualbasis.Thefifthvisittookplaceon
day60andthesixthandfinalvisitonday90.
Atthescreenandpriortorandomization,14oftheparticipantsreportedmild
headachesand"notfeelingwell".All100studyparticipantswereattemptingtocontrol
theirglucoselevelswithdietandexercise.Dietandexercisewerenotmonitoredduring
thestudy,butallparticipantswereinstructedtomakenochangesintheirdiet,
activities,orwaterintakeduringthedurationofthestudyatthescreeningandat
subsequentvisits.
Tests
ThetestsbrieflydescribedbelowwereperformedbyFenestrausingstandardclinical
procedures.
FastingBloodGlucose:Approximately7mLofvenousbloodwascollectedfromeach
participantateachblooddrawandfastingbloodglucosewasmeasured.
BodyMass:Bodymass(lbs)wasrecordedonallparticipantsatall6visitsusinga
monthlycalibratedweightscale.
GlucoseChallenge:Eachparticipant'sfastingbloodglucose(FBG)levelwasmeasured
atbaseline(day2).Fortheoralglucosetolerancetest(OGTT),allparticipantswere
givenatesttablet(halfoftheparticipantsweregivenactiveproductandhalfofthe
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participantsweregivenplacebo),followedbyastandard75gcarbohydrateloaddrink.
Bloodplasmareadingsweretakenat30minute,120minute,and180minuteintervals.
TotalCholesterol:Participant’sbloodwastakenaftera12‐14hourfastingperiod.
Participantswereaskedtoabstainfromalcoholforatleast24hoursbefore5‐19mlof
arterialbloodwasdrawn.
Lipoproteins:LDLlevelswerecalculatedbysubtractingHDLreadingsplusonefifthof
thetriglyceridesfromthetotalcholesterol.LDL=Totalcholesterol‐(HDL+Triglycerides/5).
Triglycerides:Thebloodtestwasperformedonfasting(12‐14hour)participants.
Participantswereaskedtoabstainfromanyalcoholfor24hoursbeforethetest.Fiveto
10mLofvenousbloodwasdrawnfromeachparticipantateachtestinterval.
BloodPressure:Bloodpressurewastakenbymedicalprofessionalswithaminimumof
20yearsexperienceusingasphygmomanometerandstethoscope.Bloodpressure
measurementsweretakenanaverageofthreetimesafteraminimumrestofatleast15
minutes.
HemoglobinA1c(HbA1c,Glycohemoglobin,Glycatedhemoglobin,Glycosylated
hemoglobin):BloodwasdrawnonDay1andDay90.Anarterialbloodsamplewas
obtainedbyinsertinganeedleintoanarteryoftheparticipant’sarmandastandard
HbA1cvialofbloodwascollectedbyahealthcareprofessional.
Statisticalmethods
Continuouslydistributedoutcomesweresummarizedwiththemean±onestandard
deviation.Treatmentgroups(DiaMetrix,Placebo)werecontrastedonthemeanof
continuouslydistributedoutcomesusingrepeatedmeasureslinearmodelsofthe
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outcomeintermsoftime,treatmentgroup,andthetimebytreatmentgroup
interactionwithanautoregressiveorder1autocorrelationmatrix.Allstatisticaltesting
was2‐sidedwithasignificancelevelof5%.RVersion2.11.1(RFoundation)wasused
throughout;tableswerecreatedusingSASVersion9.2forWindows(SASInstitute,Cary,
NC).
RESULTS
Allparticipantscompletedthestudy;therewerenomissingdata.
DemographicCharacteristics:Treatmentgroupsweresimilarwithregardtothe
proportionmale[DiaMetrix22(44%),Placebo25(50%)]andmeanage(DiaMetrix
43.5±12.7,Placebo45.8±10.8,p=0.32)andthepercentageofsubjectsofthewhiterace
wassignificantlydecreasedamongthoserandomizedtoDiaMetrix(DiaMetrix24(48%),
Placebo37(74%),p=0.01);seeTable1.
FastingSerumGlucose:Treatmentgroupfastingglucosemeans(ng/dL),showninTable
2andFigure2,weresimilaratbaseline(DiaMetrix196.6±17.5,Placebo196.9±17.4,
p=0.93)whereastheDiaMetrixmean(14days:DiaMetrix96.6±10.3,Placebo
205.5±30.7,p<0.001;30days:DiaMetrix96.5±11.0,Placebo204.9±21.6,p<0.001;60
days:DiaMetrix94.8±10.1,Placebo209.4±22.5,p<0.001;90days:DiaMetrix89.4±9.2,
Placebo205.2±20.2,p<0.001)andmeanchangesfrombaseline(DiaMetrix‐107.2±14.5,
Placebo8.3±14.8,p<0.001)weresignificantlydecreasedat90days.
HbA1c(%):TreatmentgroupHbA1c(%)means(Table2)weresimilaratbaseline
(DiaMetrix7.7±0.5,Placebo7.7±0.5;p=0.93)whereasthemeanat90days(DiaMetrix
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4.7±0.3,Placebo8±0.6,p<0.001)andthemeanchangefrombaselineto90days
(DiaMetrix‐3.0±0.5,Placebo0.3±0.4,p<0.001)weresignificantlydecreasedinsubjects
takingDiaMetrix.At90days,nosubjectwhoreceivedDiaMetrixhadanHbA1cabove
5%.Incontrast,at90daysnosubjectwhoreceivedPlacebohadanHbA1cbelow6.9%.
GlucoseChallengeTest(ng/dL):TheDiaMetrixmeanserumglucose(Table2)was
significantlydecreasedrelativetoplaceboat30,120and180minutesafterthe
challenge(30minutes:DiaMetrix110.1±24.1,Placebo205.1±18.5,p<0.001;120
minutes:DiaMetrix110.0±23.0,Placebo221.9±14.6,p<0.001;180minutes:DiaMetrix
109.5±23.3,Placebo225.8±12.6,p<0.001).
Triglycerides:Treatmentgrouptriglyceridesmeans(mg/dl),seeTable2andFigure1,
weresimilaratbaseline(DiaMetrix255.2±48.1,Placebo254.5±46.5,p=0.95)whereas
theDiaMetrixmean(30days:DiaMetrix234.6±50.2,Placebo259.3±45.4,p=0.01;60
days:DiaMetrix213.9±44.4,Placebo269.6±48.1,p<0.001;90days:DiaMetrix
203.2±42.4,Placebo271.3±48.3,p<0.001)andmeanchangesfrombaseline(90days:
DiaMetrix‐52.0±23.7,Placebo16.8±28.6,p<0.001)weresignificantlydecreasedat90
days.
TotalCholesterol:TheDiaMetrixmeanCholesterol(µg/dL),seeTable2,was
significantlyincreasedatbaselinerelativetoplacebo(DiaMetrix:338.5±96.9,Placebo:
301.3±89.4,p=0.01).ThetreatmentgroupCholesterolmeansdidnotdiffersignificantly
at90days(90days:DiaMetrix240.0±32.8,Placebo261.2±29.2,p=0.13)whereasthe
DiaMetrixmeanchangefrombaselinewassignificantlydecreasedrelativetoplacebo
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(changesfrombaselineto90days:DiaMetrix‐98.5±110.0,Placebo‐40.1±99.6,
p=0.004).
HighDensityLipoproteins(HDL):TheDiaMetrixmeanHLDL(µg/dL),seeTable2,did
notdiffersignificantlyfromtheplacebomeanatbaseline(DiaMetrix:56.8±29.8,
Placebo:57.3±29.8,p=0.93)orat90days(90days:DiaMetrix47.7±9.3,Placebo
52.6±10.5,p=0.28;changesfrombaselineto90days:DiaMetrix‐9.0±33.6,Placebo‐
4.7±35.0,p=0.45).
LowDensityLipoproteins(LDL):TheDiaMetrixmeanLDL(mg/dL),showninTable2,
wassignificantlyincreasedatbaselinerelativetoplacebo(DiaMetrix:230.7±106.9,
Placebo:193.2±87.2,p=0.01)whereasthetreatmentgroupLDLmeansandmean
changesinLDLdidnotdiffersignificantlyat90days(90days:DiaMetrix151.7±33.5,
Placebo154.4±30.3,p=0.86;changesfrombaselineto90days:DiaMetrix‐79.0±120.8,
Placebo‐38±94.9,p=0.11).
RatioOfTotalCholesterolToHighDensityLipoproteins:TheDiaMetrixmeanratioof
totalcholesteroltohighdensitylipoproteins(Table2)didnotdiffersignificantlyfrom
theplacebomeanatbaseline(DiaMetrix:8.5±5.9,Placebo:7.2±5.1,p=0.10)orat90
days(90days:DiaMetrix5.3±1.5,Placebo5.1±1.1,p=0.88).
RatioOfLowDensityLipoproteinsToHighDensityLipoproteins:TheDiaMetrixmean
ratiooftotalcholesteroltohighdensitylipoproteins(Table2)didnotdiffersignificantly
fromtheplacebomeanatbaseline(DiaMetrix:6.2±5.2,Placebo:4.9±4.3,p=0.06)orat
90days(90days:DiaMetrix3.4±1.3,Placebo3.1±0.9,p=0.65).
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SystolicBloodPressure:TheDiaMetrixsystolicbloodpressuremean(Table2)was
significantlyincreasedrelativetoplaceboatbaseline(Baseline:DiaMetrix171.3±19.9,
Placebo155.2±25.1,p<0.001),whereasthetreatmentgroupmeanswerenot
significantlydifferentat30and60days(30days:DiaMetrix157.9±25.9,Placebo
154.2±21.4,p=0.37;60days:DiaMetrix149.7±16.3,Placebo155.4±19.4,p=0.16)and
theDiaMetrixmeanwassignificantlydecreasedat90days(90days:DiaMetrix
142.9±14.6,Placebo155.2±18.9,p=0.003).Analysesonchangesfrombaselineshowed
significantlydecreasedmeanchangesfrombaselineto90(p<0.001)daysinsubjects
randomizedtoDiaMetrix.
DiastolicBloodPressure:Treatmentgroupdiastolicbloodpressuremeans(mmHg),see
Table2andFigure3,weresimilaratbaselineandat30days(Baseline:DiaMetrix
75.2±9.9,Placebo76.0±8.7,p=0.55;30days:DiaMetrix74.5±6.4,Placebo75.5±6.9,
p=0.44),whereastheDiaMetrixmeanwassignificantlydecreaseat60and90days(60
days:DiaMetrix71.9±4.3,Placebo76.7±5.7,p=0.001;90days:DiaMetrix70.3±3.2,
Placebo76.6±5.2,p<0.001).Themeanchangefrombaselineto90dayswas
significantlydecreasedinsubjectsrandomizedtoDiaMetrix(p<0.001).
BodyMass:TheDiaMetrixmeanbodymass(lb),seeTable2,wasnotsignificantly
differentfromtheplacebomeanatbaseline(DiaMetrix:211.4±54.7,Placebo:
211.6±53.6,p=0.99).Thetreatmentgroupweightmeansdidnotdiffersignificantlyat
90days(90days:DiaMetrix202.1±54.0,Placebo211.6±52.8,p=0.38)whereasthe
DiaMetrixmeanchangefrombaselinewassignificantlydecreasedrelativetoplacebo
(changesfrombaselineto90days:DiaMetrix‐9.3±3.1,Placebo0.0±2.9,p<0.001).
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Discussion
Thisstudyinsubjectswithpre‐diabetesanddiabetesdemonstratedstatistically
significanteffectsofDiaMetrixonfastingglucoselevelandtheglucosechallengetest,
HbA1c,andbloodpressure.TotalcholesterolwasdecreasedbutLDLandHDLwerenot
significantlyaffected.Withrespecttobodymass,DiaMetrixtreatmentgroupmean
changefrombaselinewassignificantlydecreasedrelativetoplacebo.
Basedonthemagnitudeofclinicalresponses,DiaMetrixcomparedfavorablyto
standardtherapeuticsusedintreatmentofdiabetes.Metforminisoneoftheoldest
anti‐diabetesdrugsandwasclaimedto"lowerthebloodsugartominimum
physiologicallimit"intreatedpatients.Basedonitsfavorabletoxicityprofileitwas
widelyusedbutwasapprovedbytheU.S.FoodandDrugAdministrationfortype2
diabetesin1994(6).MedianHbA1cwas7.4%intheMetformingroupcomparedwith
8.0%intheconventionalgroup,andintensiveglucosecontrolwithMetformin
decreasedtheriskofdiabetesrelatedendpointsinoverweightdiabeticpatients,and
wasassociatedwithlessweightgain(6).Pioglitazone(Actos),adruginthe
thiazolidinedionefamily,selectivelystimulatesthenuclearreceptorperoxisome
proliferator‐activatedreceptorgamma(PPAR‐γ)andmodulatesthetranscriptionof
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insulin‐responsivegenesinvolvedinthecontrolofglucoseandlipidmetabolism(7).
Actossignificantlydecreasedfastingplasmaglucoselevelfrom11.0+/‐2.0mmol/literto
8.9+/‐1.1mmol/literwithasignificantimprovementinthehemoglobinHbA1clevel
from9.2+/‐1.8%to8.3+/‐1.5%(11).Rosiglitazone,anotherthiazolidinedioneoral
antidiabeticagent,hasbeenshowntosignificantlyreduceHbA1candfastingplasma
glucoseunderdifferentdosingregimens(8).Exenatideisasyntheticversionof
exendin‐4,ahormonefoundinthesalivaoftheGilamonster.Itdisplaysbiological
propertiessimilartohumanglucagon‐likepeptide‐1throughregulationofglucose
metabolismandinsulinsecretionbutitsmechanismofactionisstillunderstudy[2].A
52‐weektreatmentwithexenatidereducedHBA1Cby−0.8±0.1%(9).
Atpresent,themanagementoftype2diabetesfocusesonglucosecontrolthrough
loweringofbloodglucoseandbyextensionHbA1candotheradvancedglycationend
products(3).Inouropinion,theseclinicalendpointsaresymptomsofdisease,not
diseasemechanisms.Persistenthighbloodsugarinpeopleisaproblem;however,even
withperfectglucosecontrolpeoplestillsufferfromsignificantorganpathologies,
morbidityandmortality.Drugsthataredesignedtocontrolbloodsugarhavemany
liabilitiessuchasinductionofhypoglycemia.Thusthecommonlyacceptedemphasison
controllingbloodsugarasasoleendpointmaybesomewhatmisguidedinthatblood
sugarlevelisonlyoneofthemultiplefacetsofdiabetes.Wefeelthatmoreemphasis
shouldbeplacedoncontroloftheimmunedysfunctionthatisamajorbiochemical
driverofthepathologyofdiabetes.Therefore,understandinghowdrugsimpact
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inflammatorybiomarkerprofileswillbeextremelyimportantinunderstandingand
treatingdiabetes.Weproposethattheoptimaltherapeuticstrategyfordiabetesshould
addressnotonlybloodsugarcontrol,butalsobedirectedtocontrolofimmunesystem
imbalanceinaefforttodelaydiseaseprogression(3).
Giventhattype2diabetesisfundamentallyaninflammatorydisease(2),inourrecentin
vivostudyinamodelofhumantype2diabetesinobesemice,weselectedabroad
rangeofendpointstoevaluatemechanismofactionofDiaMetrix.Inadditionto
commonlytestedmetabolites(glucose,advancedglycationendproduct,insulin,
cholesterol,triglycerides),weincludedpyruvatekinase,hexokinaseII,andcitrateas
potentiallyrelevantendpointsalongwithalargepanelofcytokines,chemokines,
endocrinemarkersandgrowthfactorsandhaveshownthatofDiaMetrixsignificantly
downregulatedseveralpro‐inflammatorychemokines,cytokines,andgrowthfactors
andupregulatedlevelsoftheanti‐inflammatorycytokineIL‐4.Wespeculatethat
DiaMetrixmaybreaktheselfreinforcinginflammatorycycleandthusslowdownthe
naturalcourseofthedisease(Hampshireetal.,submitted).
Inconclusion,thisstudydemonstratedareductioninthemeanfastingbloodsugar,
bloodpressureandbodymassinsubjectsrandomizedtoDiaMetrix.Thesefindings
suggestthatDiaMetrix,anover‐thecounterpreparation,deservesfurtherevaluationof
itsactivityinlargerclinicalstudies.
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Competinginterests
KRH,SM,andRMareownersofSyntraTech.
EI,RTS,JM,andCLareconsultantsforSyntraTech.
Authors'contributions
KRH,SM,andRMfundedthestudyandanalysisoftheclinicaldata.
JMandCLperformedstatisticalanalysisoftheclinicaldata.
EI,JMandRTSreviewedtheresultsandwrotethemanuscript.
Page19of20
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DiaMetrix Human Study (14 October 2010)
Table 1. Demographics
Syntra-5 (N=50) Placebo (N=50) Total P-Value
Male [N (%)] 22 (44) 25 (50) 47 (47) 0.691
White [N (%)] 24 (48) 37 (74) 61 (61) 0.011
Age (Mean ± SD) 43.48±12.68 45.82±10.77 44.65±12 0.322
1Pearson's Chi Square Test 2F Test for treatment
CL - Page 3 of 3
Human Study (14 October 2010)
Table 2. Blood Chemistry
Outcome (Mean ± SD) Time - (N=50) Placebo (N=50) Total P-Value
High Density Lipoprotein (?g/?L) Baseline 56.8±29.8 57.3±29.8 57±30 0.931
Day 90 47.7±9.3 52.6±10.5 50.1±10 0.282
Change from Baseline to Day 90 -9±33.6 -4.7±35 -6.9±34 0.452
Low Density Lipoprotein (?g/?L) Baseline 230.7±106.9 193.2±87.2 212±99 0.011
Day 90 151.7±33.5 154.4±30.3 153±32 0.862
Change from Baseline to Day 90 -79±120.8 -38.8±94.9 -58.9±110 0.112
Ratio of Low Density Lipoprotein to High Density Lipoproteins
Baseline 6.2±5.2 4.9±4.3 5.6±5 0.061
Day 90 3.4±1.3 3.1±0.9 3.2±1 0.652
Systolic Blood Pressure (mm Hg) Baseline 171.3±19.9 155.2±25.1 163.2±24 < 0.0011
Day 30 157.9±25.9 154.2±21.4 156±24 0.372
Day 60 149.7±16.3 155.4±19.4 152.6±18 0.162
Day 90 142.9±14.6 155.2±18.9 149±18 0.0032
Change from Baseline to Day 90 -28.4±17.1 0±10.5 -14.2±20 < 0.0012
Diastolic Blood Pressure (mm Hg) Baseline 75.2±9.9 76±8.7 75.6±9 0.551
Day 30 74.5±6.4 75.5±6.9 75±7 0.442
Day 60 71.9±4.3 76.7±5.7 74.3±6 0.0012
Day 90 70.3±3.2 76.6±5.2 73.5±5 < 0.0012
Change from Baseline to Day 90 -4.9±9 0.7±6.5 -2.1±8 < 0.0012
Weight (lbs) Baseline 211.4±54.7 211.6±53.6 211.5±54 0.991
Day 90 202.1±54 211.6±52.8 206.8±53 0.382
Change from Baseline to Day 90 -9.3±3.1 0±2.9 -4.6±6 < 0.0012
1F Test for treatment 2F Test for treatment based on a repeated measures ANOVA in terms of treatment, time and treatment by time and an AR(1) correlation structure (treatment by time interaction: p-value < 0.001).
DiaMetrix
DiaMetrix
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Table 2. Blood Chemistry
Outcome (Mean ± SD) Time Placebo (N=50) Total P-Value
Fasting Serum Glucose (mg/dL) Baseline 196.6±17.5 196.9±17.4 196.8±17 0.931
Day 14 96.6±10.3 205.5±30.7 151.1±59 < 0.0012
Day 30 96.5±11 204.9±21.6 150.7±57 < 0.0012
Day 60 94.8±10.1 209.4±22.5 152.1±60 < 0.0012
Day 90 89.4±9.2 205.2±20.2 147.3±60 < 0.0012
Change from Baseline to Day 90 -107.2±14.5 8.3±14.8 -49.5±60 < 0.0012
A1c (%) Baseline 7.7±0.5 7.7±0.5 7.7±0.01 0.931
Day 90 4.7±0.3 8±0.6 6.3±2 < 0.0012
Change from Baseline to Day 90 -3±0.5 0.3±0.4 -1.4±2 < 0.0012
Serum Glucose (mg/dL) Minute 30 110.1±24.1 205.1±18.5 157.6±52 < 0.0011
Minute 120 110±23 221.9±14.6 165.9±59 < 0.0012
Minute 180 109.5±23.3 225.8±12.6 167.6±61 < 0.0012
Triglycerides (mg/dL) Baseline 255.2±48.1 254.5±46.5 254.9±47 0.951
Day 30 234.6±50.2 259.3±45.4 247±49 0.012
Day 60 213.9±44.4 269.6±48.1 241.7±54 < 0.0012
Day 90 203.2±42.4 271.3±48.3 237.2±57 < 0.0012
Change from Baseline to Day 90 -52±23.7 16.8±28.6 -17.6±43 < 0.0012
Cholesterol (?g/?L) Baseline 338.5±96.9 301.3±89.4 319.9±95 0.011
Day 90 240±32.8 261.2±29.2 250.6±33 0.132
Change from Baseline to Day 90 -98.5±110 -40.1±99.6 -69.3±108 0.0042
Ratio of Cholesterols to High Density Lipoproteins
Baseline 8.5±5.9 7.2±5.1 7.8±6 0.101
Day 90 5.3±1.5 5.1±1.1 5.2±1 0.882
1F Test for treatment 2F Test for treatment based on a repeated measures ANOVA in terms of treatment, time and treatment by time and an AR(1) correlation structure (treatment by time interaction: p-value < 0.001).
DiaMetrix Human Study (14 October 2010)
(N=50) DiaMetrix
Figure 1 Mean triglycerides (mM) by treatment group (Blue: DiaMetrix- , Black: Placebo); whiskers extend
to the mean ±1 standard deviation. The treatment by time interaction was significant (p< 0.001);
treatment group contrasts on the mean were significant at 30 (p=0.01), 60 (p<0.001) and 90 days
(p<0.001) based on a repeated measures linear model with an autoregressive order 1 covariance
assumption.
Figure 2 Mean fasting serum glucose (ng/dl) by treatment group (Blue: DiaMetrix, Black: Placebo);
whiskers extend to the mean±1 standard deviation. The treatment by time interaction was significant
(p<0.001); treatment group contrasts on the mean were significant at 14 (p<0.001), 30 (p<0.001), 60
(p<0.001) and 90 days (p<0.001) based on a repeated measures linear model with an autoregressive
order 1 covariance assumption.
Figure 3 Mean diastolic blood pressure (mm Hg) by treatment group (Blue: DiaMetrix- , Black: Placebo);
whiskers extend to the mean±1 standard deviation. The treatment by time interaction was significant
(p<0.001); treatment group contrasts on the mean were significant at 6 (p<0.001) and 90 days
(p<0.001) based on a repeated measures linear model with an autoregressive order 1 covariance
assumption.
0