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Scveral sr-r.:dies (see thc recent feview lty Colvnu and FLq.Luslc,tto) havc demonstrated a nurober of abnotrralities i1 the l"rernostasi.s tcsts in cliabetes, Thcsc firrdings led to thc suggestion uhar rn inctcascd thrombotic terrdcncy might play. a pnnafo pathogenetic lule in the onse[ of large- and smrill-vcsscl dise*sq. On thc otlr", Éur.ì, tÀ* ohrrorma.lities {ound in dinl*tics might ire a refl.ection of Foor metabohc conttol nnd/or a secondary developme'rt of vascular disease, Altfrough É*. prospectivc studies are necdcd to solve this dilernma, the combined cvalua- tjon of hemostatic parnfiÉters and mcasutetoents that express the degree of conttol of glucosc -lligh and li1.'icl rrretairolisn should hclp to rcvcal relutionships'

levels of L*roglobin A, (i-IhAr), which rÉsult from trotr-enuvtnatic post- syoth*íi. glycosylation oÈ hcmoglob.in, are thought to reflect tlre integtatecl glucosc ctnccntrarion during the previou* 2-l r:ronuhr und thc dcgree of metabolic confrol'1' figh density lipopÀtetnJ.hol*rt*rol (I-IDL-C) was found to bc invcrsely corrclated ,o ".orunory-

h"iri disease, rrnd this is considered to be ;rn i*dependtnt risk fec' tor 1r,r0,is- Èeta-rhromhoglobulig (B.TG), o platelct.spccific protein cxtrudtci ilto pirr-, <luring the releasc reaction, is a sensitive index of plnLeler activations, hinully, tiact.rl-Vlll relatcd. antigen (VIIIR;A8), 'r componcnt of the factot-Vlll

*ol*.,.riar cornplcxT, irrrs bccn piopo*"d as a natlcer Lor v*rscr:lar cndot}eliel dam- age4,ll,t*, bccituse tlr* cnclotheÍal cclls appeflr to bc the principai. sourcc of this fiomin ri- k or4er to evaluate whether clrangcs in hemostatjc vatiables 'rre cottelated

*"*rrdt: Diahetic lqmplimtion.r;.Dittbetic contrrtl.; Fatror-VllI procrtapuldttt dcliltity; .Factrtr- vili;;t-;r,[oiìisr'i, u;í,ist"ni;n A,; Hiin a*n'ity lipoprotein.choièsterol; Bùa-t]trcwboglobulin;

Triylyreildes,

Receivcdr October 24, :1.980.

Actn diabet. lrlt' 18, 19t, LtSl'

Iutituto cli Clinicrr Medica (ìcncralc c 'l'crapie Mcclisa III Univctsitù di Milano

RELATIONSI-iI PS BET!7E,EN MNTABOLIC AND I.IEMOSTA'I'I C VARIABLES IN L]NCOMPLICATED DIABETES

Canr.o Vrncin{r Grusv BBttll,lz I),trqrBrl Mant Prr,r Mnmluccro lMaNruucct

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to tfiu <legrcc of rnctabolic conttol ancf of lipid rrbnonlafities, we have choseu to uturdy th"r. reccntly proposed tcsts ancl to ielatc t.hcir tesults to othct stanclard

îÉcasurcnerits Iblo,-rcl glucose; serr.ttn rriglycerides; sentm cholesterol; factcrr-VTII

procoagulanr acrivity (VIII:C)I in a selected group of 35 patients with insulin- Jependlnt diabetes under poor metabolic conttol but withoùt apparent rnicto. arrd

DsclovÉrsflJlar i nvolverncnt.

I\IATERIATS AIVD }IETHODS

Thirty-five sulrjecrs wi.th insulín'dcpcndcnt dirrbetes tnellitus (15 wornen), on insulin ancl diet rherrrpy only, were exanrincd,

They u/ÈrÈ lged 15-38 ye*rs (mean: 29). Thc dutation of diabetes 6 to lJ year:s (mean; 8) and thc daíly insulin doses rrrnged from 10 to

men snd 20 ranged (ronr 80 U, cithct in a single dosc ot in tw<-r ot thrÈe spaced doses,

Inrulin was discontinrrcd r:n the moming of the test, IJody weight, *tpressed rts ri pÉrcenlagtr uf ideml body weight accotding t<r thr Metfolmlitnn Lifc Insurancc Company Tables, was 110 + 18 (nterrn + SD). Twclvc Paticnts wÉre smokers (10 cigarirres claiiy). All parierìts wetc asked to give up alcohol duting the mCInth hefotc testingj nanc liad hlood pressure above hortnal. Patienrs wete selected on rhe basis of the absence of vascular: complications according to thc following ctiteril:

rctinopathy wÈs excJudcd on thc basis of rhe alrsence of rníctortneurysms, hemol' rhagcs, cxudatcs or nuovascularization in both cyes after Frrpi.lJary dilatation. Neuro- Fathy was exclndecl if thete wris Èo paresrhesia and/ot atadt clrrring clinical exlrni' nntion. Nephropathy was excludcd in the aL'sence of pcrsistcnt proteinttrirr ('Al[ru' stix'-ncgativc Zi h lrite specimens) or clcvalÉrl -cerum crcatininc (<1-50 plnrol/l)- Ischemic heart s11d ccrebràuas.,rl*r discasc tnrl arterial insrrfficicncy of the limbs we.re ruled orrr by negflrive clinicai examin*tjon ancl electrocardiographic and oscil- lographic findíngs.*

The rg.-orri.h.d healrhy corrtrol snìrjects, 20 men and 20 womcn, wcte rged lB to 40 yerr:s (rrrctrn: l0). Thev wcrc not taldng rlny drugs and had no hisrory of diabrtcs ,:t of any olher diseasc that might alter platelet functjon'

Ail blood saffrplcs wete coJJected after overnight fasting,

Metdholit z,ariahles. Total cholesterol nnd ffigiycericles were tncasutecl by enzv- marjc mrethocls anrl glucose by a glucose-oxidase method (Boehringet, Mannh.+, FRG). HbAr *r, ,o-*o*ured using the cation excltange rcsin 'Bio-Rex 70', hy thc rncthod of TnrvsLLI e[ al. ". The inna-n!{sny cucftrcient o[ variation wàs 4.1'fr1- llDL-C was rletermjrred 'by

the heparin-rnanganese chlotidr ptecipitation nrethod E.

Comirlereness of prccipitation wrirr assessed by irnmunoelect::ophorcsis carriecl ortt n ITa agàrose gefstidi barbital buficr (pH 8'ó, ionic strength 0'05)'

Hemostatic uaridbles - VIIIR;Ag v/as asse$secl by quantitative immttnoelectro' phoresisró, using uronospecífic rabbit antiscrum to human factor VIII (Tstitrrto b*hdng, S.oppift-L'Aquila, lraly). VIII:C was rncasr:red by a two'Btage assay'Ó' Values-aru .*pr"*r*.} *, pet'ccntages of thosc crf pooled plasnn .frotn 20 normal subjects, ,nop.iror.n end'stored ot -ZO "C, B'TG wa$ me'Àsurecl by rndioimmuno' urroy ('Ihronboglobulin RIA kit, Itadiochcmicarl Center, Amctsham) end valucs wefe ."pr.r**d i" ogirt of plateler.Foor plasmrr, prcpared fls dcsctibed by Lunrrrlur and Cesu n.

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Fie, 1 , Relttiunship Lrerwccn VIIIR.Ag rurd f:lhA, in 15 dinbctics, Thc liue reprcscnts the lrest fitíing cutvÉ obt+ined by non-linear tegression anulysis'

and VIII:C wcre not" correlatcd to either: thc metabolic or thc henosfatic vadohlcs.

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ancl a negativc hyperÙolic tclationship with qPLIf (fiq Zl. The lattet two ftctors

shourecl ,iorilo, .Jr.*lutiur5 wirtr ViIIR:Ag/VIIITC but were not cc'treJrtted to

ttigiycer;ides. None of the resrs showe,'l nny significant cottclations in the control g t , ; " p o f h e a l h y s u 6 j e c t s . É x c e p t f o t V I I I : C t o V I I I R : A g ( * = - 0 ' 7 8 ; p < 0 0 0 1 ) '

fn... wcrÈ rrlso no significant iorrclations o[ thcsc metabo'ljc and hernostalic vati'

ables ro patiÈnt's weight at f,ge or lo the dose of insuliu aclmiuistcrcd'

DISCIJSSION

Contrasting results have previously been obtnincd wheri thc telat'ionship benpeen

HbAr and I'IDL-C was exnmin".l6'10'ie' In the Fre$ent snrc{y, no signiÉcan! invetsc

cortclation between thcsc Fàrameters wíls forrnd, whereas FIDL"C was hypctbolicaliy

related to triglycerídes, *lti.|t is in agrccmefil. with MYSRS et nl' rI and Cttnu ct al' 1:' An invers* ,"lorioo-r-hip lretween thesi vqriables iìppeats to be consistcntly obsewcd 3ó.

ancl it is *ppalcntly Lrrsed on a precursor prodrrct rclatiutrslriP l:.-tvrccn ver:y low

clensity lípoptoteinr (VfnU (which trlrnsPoft tdglycer:ides) and HI)L in the hpo'

protcin-lil.)tlse refl ction 3?.

'

O,,, ,tudy also rlemonstrates the presence ttf increased plasma levels of B-TG,

confirming rÉ.*i-ù;r.5,e,1e'r4. Howevct, high B-TG was not correlated with

HbA' CIr paraffiei.r, àt Hpid metabolisur, nraking it unlikcly thot the nbnotnrrtlity is a tutlection of rhe metsboric disturhancc, irs sr:ggestcd by Pnestc)N et rrl.3a. similnrìy,

thrtc wrts no significanr cotrclat'ion bctween R-TG and factor-VllI conrponents,

slrpFortirig the iiew th,rr B-TG dranges a.re indcpendent of othet hemostatic

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C, VERGANI, G. BETTALE, D. lvLtB.I' P, M, tr'Ci\NNUCCT

Fie, ? - Relationship bÈtween Vllllt:AS nnd I-IDL-C in 15 cliabedcs. The line represents thc bcst fit-ri"g curyc obtnineri by nou;Iincar rcgrcssi()tr onafyuis.

pnratDctÉrs, Elevnr:ed pìasnrrr levcls oi B-TG in diabetes might inclicatc in uitro rrither than in uruo platelel rtctivrttiorr, patticrrlatly whcn the rtntiplrrte.let nnticoagu' lanc providcd with thc cr:rn-tnercial radioiurnrtlnoflssny lcit is used withottt addr:d prostagldildin Er t ns was donc in thís study'

A dirprop,rttionntely gre*fe,: rise in VIIIRTAg thnn ifl VIII;C, r:esulting in an incrcascd VIIIR:Ag/Viil:C rntío, was Òbsetved in orr prltierits. I-Iigh VIIIR:Ag values were also obscrycd in previotls smdies, pattícularly in complicated clia- betes r,28.33. I'hc VIIIR;Ag and/or VIIIR:Ag/VIII:C rirtio, lrut ncrt VI]I:C, were significnntly positivcly cr.rrrclattrì to FIbAr rrnd tríglyccddcs, inclicuring that thcsc hemostatic pilrirmeters are linlcd trr the qr.rtlity of diabetic conttol as measured by FIbAr conccntratíon. A srudy of thc chmges induced in patients with poor metrùolic conrrol by continuous ínsulin infusiorr techniqucs will be r-rsefttl for {utthct valiclation of these finclíngs. However, thc observed ron-lineaf Fatterfl of the relationship igdícatcs that nrechanisms ,rther [h;lr t]re deglee of nctabo[c contro] contribute to the ahnornralitícs of factor VIII cutnponeflts in dialretics. Dtt'lsolt rl postulated that disscminatecl intrnvascular coagularion nright incteasc the VIIIR:Ag/VIII:C ratio, wherets ArrcntntAKARN ct al, I suggesfed that o taofe nrarked elevatíon of VIIIRT Ag, comparcd to rhar of VIII; C, cirtl ulso:l:c ploduccd by thc action oli protco' lytic eruytes. l,'he ahsencc of clinicrl nnd lab,lt;t1:,rry e.viderrce for díssenrÌnated iltravascrrlar coagnialron and/or increascd plastnit proceolysis nralccs thcsc possilri- litics unlikely in our prrrients. There is a repoft of a tclationslúp berween plasma growrh 6orrnone (ilF.I) ancl fnctor VIiI components in hcalthy volunfeeffir and ih.r"{urr irigh factor VIIT in unconr.rolled diabetícs rnight be rtccounted fcrt by clcvatecl GH ". H.:,wever, subsequent sqrdics by the silne investigatcts shoured no clear-cut relarjonship berween GH and (actor VIII in ctiabetics 2r. Finally, another

201

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ÀdNTANO,TIC AND IIBMTJSTATIC VARI'A,DLP'S IN DIADETES

possible explanation is thirr the sustaincd inctease of vIIIR:Ag tr:ight bc non'spccific'

simply repfesentil ;-;;il phase' rcaction tr,: d'isttrrhecl hc'meostasis 7e' VIII:C

is als' iln ircute phase rcactflnt,,-"brr* ,* ,ynrhcsis cloes not spp$at tq takc ;'rlrce in the endothel,nrt*itr-r. i:i;;;;];':-.th* d.*onstration of a greatet tise irr vIII]3:Ag thrn in yIIT:c snpporrs the ui.*ii,oiincrcasecl plasma vilIR:Ag, md puticularly u high VIiIR:AS/VIil:C rati,-r, nright b-c a conseqllÈnce of endothelÍal dnrnage and ís furdicative of vascular involvem.it, Th" negative comchtion between vIIIR:Ag end VTTIR:A*/VIII:(.,, with ffli-C providi's fur:ther i'ditect evídence that the vITIR:Ag in*ease mighr arso be olfl..ti,,n of thc Èfirent oI ùe cnclothelirtl les'itrns, because row HDL-C concenrrations ir. t

"o*n to bc associatcd wirh a high incidence of isclremic herrrt díscasert anrl ,h..,*, presnrnebly, with the ptcsence o{ ex'tensive vascular involvcmcnt. TIre ntru*o.* ní ietectable cornplicntions h our paticnts does nor invaliclate such iì viÉw, lr".r,-rr*-rhe clinir.al arrd-insttrtmentsl ctiterirr adopted cahilor u.r.[c or_rr with certainry iÀ. pt**.I.* ni. crinically rnute vascular lesions.

Provided thar otL*r st'díes .oifit* di" u*lu" of VIIIR:Ag as an inditect indcx of endotl,cfid ,Jamage, thc **o*or**ìnt migl:t have long-refP progn.stic significzurcc ancl this coulcf ..,**hrlly be ascert*ined by 4 Prospcctive st'dy'

SUMIyÍARY

$cvetal rnctaholic (IIbA,, IÍDLC, ttigìvccti4ss). anc{ hernostutic (ViIIR:AS' VI-Ii:C' B-TG) variublcs were investigrrerl in ]I 'on-rl"r!;.i"JGdefeuclent ciiubctics withotrr clinicallv e'idcnt vasctrrnr corupricarjrns] B-TG.wus lriqlr bttt'cìicr not cnir.Li-e-wrth orl'"" tnetabolic snd hcintstqtic

bsriunc.ters, suggcsting rhat ctcvqted E-Tli';'ìifiúr;; --t-_gltr, ir. * cxpîcssion ol in ritro pltrtelct'

*rcrivati'n. VIIilt:A,{-ancr tlre ,qtio ,* viliti,{l.;-.wII*{. r.t, marLedly increasecl' '['l'rete srnr

a sinnificen, ...rr.t#ll,"1i ;h; Hi5A, ;;i iiijlci*tt' *iirì villn'af iniicnri''g thnr vIIIR:As

is anothet re0ecrjon o{ mcteholic c*rntr,il *'TiJ.q.r.._A.ddiriond-.path()pnic mechurúsms, howevff,

#;;;; ú--i*iff".lii'"I"*ioì it. .t.'n'''s,.s i' VIIIR:As in diubctcs'

A CKI'IOV I,ÉDGEAIFN'I'S 'w'c

ere grurrtly in.{ebtccl -t., .M.T. Motetto, -Ph-l)', Lecturet in 'l-fistorv of strrtistics' at B*cconi universiry'of Mlur, {rrt }rer i.rÌr;il'tho *."iistùi:iì,ntunrioo Tln r*pert tcchnicul assisrauce ut ErrurtL'o'n*orfj"il;r;-i:r,,rdrri;;; v;;.J' i; uiso st{telntlv acknowlerlged'

RAFERENCÉS

1) AîI{}TARTAKARN Y, il{n*.* v.J., Krnlv E'F,'.Bnuuzvnsnr A Z'r F'ffccts of e'zvtntrtic tlesredetinn .,n the' sub,rnir .o*l,jrilùori *à'ùiàf"eic ptoperU*s of hrrrnen Factot VIIL - Èlùxf 5I, 2E:1, l97B'

2 ) B l , o o u A . L ' : . P l r y s i u l o g y o f F a c t o t v I l I - ] t r l P o r r r + x L . ( E r l , ) : R e c e n t l r h ' a f l C € g i n h l o o d -'

."JJn totiool Criuichiii tl'iuiugstonc' Edinburgh' 1971 ; p' ['59'

l) Bor,ron A,E., Luor-.rÀr c A,^MOOnn s., Purrgt D.,S', c*srr J'D',: 'I'lrrec appronchcs to thc rarlioimtnundt;; "r il;; hfih;;boelnb"litt ' Btit"'f ' tlectrrrt ' J'l' zlJ' 1j76'

4) BoNsu 8,, Altel M., Pr.lnTE J., Brnnus R,; Fuctor vIII complex uod entlothc'lial clamage - Laflc€t 1,141Q, t975'

J) Bonsav D, (J., l]evr,s J ,..F.trnsrn D' M', P19qsr C v ' Elrot't R' A" (}*'nxt R' lr': Plnss'e bera.rhromhrslobulin in ,Iiab"t.r'tnilifìl"l:'r:i"Uutoi"gir l.B, l-51, 19S0'

(,) BoUCnnt 8.J., Yutrrru J,: Diuberic control and HÙL cltolcstctol lcvcìs - LnnCet 2' 269' 7i78' 7) Bnozrrvlc M.: Physiological mechnnìsms ifl cosgulatiorr *.rrr'l f-rbri:rolyris - Btit rned' Bu]l' f-l'

21r, 1917,

8) Bunru.stElN M., Srlal'r-l.,t.u r.,: S,rt.-rrr-dos_t4e-':Pj.I* du cholcstéto] ]iÉ 8u]r G- ct eufi i3-iiptl- protsrtrs uu t*i'til - Uin' ciri- Actq Í' ó0?' 1960'

2 0 4

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c. VERGANI, G, nEîTAr'F., D- MARI, P. M. À

Bunxr)ws A,W,, Cr+lvrN $,L, I{or,'x,rnlt T.D.R.: Pls$ma-thnrurbugh'buliu LuucÈlrttillions in díabctcs mcllitus - Lancct 1,215,1978'

CA,.vF.r{,r, (,ì, T),, (-irlHArra J, J., Mlrnnn T., Wr.su P. Il., Ynrrus. R .A , ES-1;^ts ol thernpy on plarma high-dcnsiryJipopiotiin cholestetol concenttnticru in dirrbetes mellittts - Lensct ?, 66, 197E,

futs1eru W, P., ,l)ovr,q J,, Gonnorq T., H.rurs C. G., Il;trn'tr-mu M. fj,, Htlr.t.rs S- B-, Kft;N 4., ztìuit W, J.: iiOf cholestetol and othet lipids in coronrqy henrt discnsr.. The Cooperative Lipgplrtein PhenotyFiîIs Stucly - CÍrculation i5,767, L977,

CHA!{ M,K,, VmcH.usR 2,, Pr.nsnrru J. V/., MooRlm,tn.1.F.: Do plusmu ttiglycerides rcgulate high-density lipoproteius ot vice versnl . Lancct 2, J05, 1979,

Correr 8.S,, fhnm R.N., Mrlrow R.C., GnAr.,r{rcr H.R.; Plasrurr cofactors of platclet fr*.tióo' coriclation with rjiabeLic retinoprthy ond haer:oogJobin Ara-c ' Ann, intctn- Med.

88, 311, 1978.

Cor.vnr.l J. A., H.rr,usrcA P. V.: Platelct function in diabctcs tneiljtrrs - Btit. J. Htremnt. 44, 5 2 1 , 1 9 8 0 .

Coxnr R,, Arnpulr M., C,roccr L., lvf,tnuucr;r P.M,: .An incrensed fsrror VTTI antigÉtl tls nn inclicatot of enclotlrelial datnuge in mcnsles. Thrombos, llcs, 14,805, 1979-

.l)r,usoi:l W. W,.h,.: 'l'echnique$ - In: Brccs R, (lid.): Fluman blorxì coagrrlition, hemostasis ancl thrombosis, Blaclcwell Scietrtifr Publications, Oxford4dinbr.rrgtr, I97ó; n.475-

Dnruson K. W,lr,: Lhc ratip rrt fackrt Vlll-rrluted ur:tigen nud fnctor VTTT hiologicd àcrivity ss fln indcrq of hypctcougulubiJ-iry and i-urrnvasculnr clotting . Thrombou- Rcs. I0, L07, 1177.

.[gnk6 M,E,, Nrl,ssor{ I.M., Lrurr.r. F,: Sier:ificnucc of incrcascd faqtor VIII in enrly gltrmerulrrnephritis - Arrrr. itrterrr. Mcd, 8J, J37, 7975.

Er,.r+É.r.Es R.S., \X/u J.,'T{ervrnrnv J.: Hrrernoglobin Al, blood glucose ancl high-deusitv Jipoprotcin cholcltqrul in insuli.u-teqr-riring clinbetics . J,ancct 2, 147, 1978-

l,'1sHF,R lt, A.: Strtisticd methods for rcscrrch workcrs - Oliver end Boyd Ltd., Jidinhutgh, 1950.

G13uly K.I-L, l;.nsrv K., Bnt,stfiv J L,, ElltSON U, lt., .Br.riUr'r IT.F., G,tlrcr I.M,:

Ciyi"iytriia f,à.*ost,rbins antl long-telr:n bloocl glrlcosc connr.rl in riiahetes nrcllilus ' J. clin.

E n d o c r , 4 4 , 8 5 9 , 1 9 7 7 ,

Gonur1 I3,, l[urnnsrETN A. H.: Huer:noglobin Ar und diabctcs mcltirus - Dicbetoiogin .7.5, r, 197E.

GoÀ171lts J., Colssp"r.r,J.A., .$nnp K. 8., N,rrn R. M. G, S.l-qu-fJ i--Eiect of .mctabolic qrrttuol

*i* iit"tin'on ptor*r, von Wiilcbr"nci {"ct,:t dctivity (VIiIR:V/F) in diabctes meLlitus' Thonbos. Rcs. 72, 161, 1980.

Juru ll, A., I-Iovzn L.Tfl., NlCnnaarv R, Ij,: $rmth6is of antihemophilic Joctor untigcn by iujtuterl hurorur endothelial cclls - J. c.hn- Inveut- 52,2757' 1973.

Kol A.; Acule phrrse protci.us - In: Alr.tsou C.A. (Ed^); Structure und functíon of plusr:tr protcins. Plef.rurr Ptess, Lonrlou, 1974; P'7J.

Llunsl.l, C. B,: Eles*ttinrmurosssfly - Scancl. J, clin, Lab. Invest. 29 (Suppl. 124), 2L, 1972- Lull,nl,r C. A., Crur J, D,: Stqdics on the telease uÉ fl-thrcurboglobulin from htrtnan plateletr in aiao - Btit. J. H*emat, J],219,t976-

Lursru :tj. G,, F,tss D. N., (J'FlLl,oN w, M , Bawrs E. J, W.: Incrensed von \f/illebtsnd factor irr diuhetes rnellitus . Mctabolisrn 28, 61, 1979,

Mlrrrrcws J.H,, O'CI)NNóI( J !',, lleenlrs4+lr J,rR., pqol.J-K-' -Bcta.Jhtotuboglobrriin end glycosyiited hacmoglobin in disbetes mellitus. Scand, J' I'lacmat' 2.1,421' 1979'

Mr:,lrn C,.T,, Mrr,r,p,n N.E.: Plrrsma"i:igh-dcnsity-liprrptotein cont:enkution rrrrd deveiopmcnt oI isr-:lrrrcruii heatt-dircase ' Lrulccc f , 16' 1975.

lI) Myrns L,H,, Psrr.r,rps N.R., FIevsL R..1,:.Mathcmatical waluatíon of tnethocls lor estima- tiorr oI the ionccntration of

't]re

mujor lipid compohehts r,:{ human seruat lipoprotcins - J.

1 1 )

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24)

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Lab. clil, Mcd. .Î8, 491, 1976'

hTrxrrlÀ E,A,,, TlsrnrsN M.-R,, I{exxt chalestc,rol to lipoptotein'lipasc activiT

Athcrqeclctosis 2.9, 497, 1978-

M,: lleJetion of pla.,irrrs high-density lipoprotein in udipose tissue a:rd skeletnl mttsclc of tnan '

.1.1) Prmowr M., .r\r,naBt ' L., Ilorunrnc L,: Incrcascd von \SiJlebrenql atrtihemophilic fnctor A in dirrbetic retinopnthy - Acta oplithal. (Kbh') J2,821, 1914'

205

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METAtsO',IC AI{N IIEMOSTATIC VARIAELEs IN TTIABETÈ'S

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15) Srnlr K,E., LgvrNl' S'H,, NerLR'M'G'"Src"'r J" Ct)Lvllr' J'A'; Ilelstion betu/eefl growrh t.,ur*on'*"i.'u-*l; *,1

"o"-Wiff*6t*rid'+i.lot

u.ii'uity - i- cI$ E'docr' 45' 851' 1977 ' ] 6 ) S c p , t E r i r É n E - J . , L r ' ' n r . 4 ' t ' , A l n n n s o s D E ' - I J ' $ N E R R ' N " I J n ' É v e R H ' B " H L ' { c l f f i T L D c n

W. c.; ptasmrr-tiiglycerirlcs . ,**,1'1-uu,iì'I"r-iìùL-.f"i"*r*Ài'ic'rcls ' I'encei ?' i91' 1978'

37) Tnrvrru L,A,, Rn**or I-.l..Ml Lnr H'T-: Flctnoglobin components in padcnts wrth

cliabetes Docllit; "-N;;-Errsl' I' Mcd' 284' lJJ' 1971'

ig) vetoem c,, TnovAîo G-,, DroCUrtnor N.l s-q$*.trrul lipids, Iipopr'tei. cholesrerol' tìpo"

proteir, A and'Èiii^.rrJiór*."iot'il,**;- Ltio, .t itn. Acîa 87, L27, Lf78'

Rcr;re,t/.r for reprints showld be addresxd to"

Crtkr.o Vntritwr

Isrilrlrn di C\hica Medica GenercIc t TeraPia Medica III

V ì a P a c e , 7 5 201'00 Milano - ItalY

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