wexi™o±ssr—el ƒymposium

iffe™ts of istrogenGwedrogestone „her—py on the epoprotein

fEgont—ining vipoproteins in €ostmenop—us—l ‡omen with

„ype P hi—˜etes wellitus under ƒ—tisf—™tory —nd

xonEs—tisf—™tory qly™emi™ gontrol

g—rlos el˜erto eguil—rEƒ—lin—s whD ynix erit— welzer whD veo˜—rdo ƒ—uque ‚eyn— whD

engelin— vopez fƒ™D w— vuis— †el—s™o €erez ‚xD vuz iF quillen fƒ™D pr—n™is™o t—vier qomez €erez

wh —nd tu—n eF ‚ull ‚odrigo wh

hep—rtment of indo™rinology —nd wet—˜olismD x—tion—l snstitute of wedi™—l ƒ™ien™es —nd xutrition ƒ—lv—dor u˜ir—nD

wexi™o gityD wexi™o

uey wordsX di—˜etesD estrogenD sm—ll dense low density lipoproteinD hypergly™emi—D progestin

xumerous studies h—ve demonstr—ted th—t p—tients with type P

e˜str—™t

di—˜etes h—ve —n in™re—sed ™—rdiov—s™ul—r riskF woreoverD

f—™kgroundX snform—tion is l—™king on the effe™ts of

™—rdiov—s™ul—r events —re the most frequent ™—use of mort—lity

hormone repl—™ement ther—py in women with di—˜etesD

in this disorder ‘I“F „here —re sever—l expl—n—tions for the

espe™i—lly during moder—te ™hroni™ hypergly™emi—F

development of —theros™lerosis in type P di—˜etesY some ™ould ˜e

y˜je™tivesX „o study the effe™ts of r‚„ on the lipid profile

modified with proper di—gnosis —nd tre—tmentF „he lipid

—nd the low density lipoprotein su˜™l—ss distri˜ution in women

—˜norm—lities f—ll into this ™—tegory ‘PDQ“F wore th—n US7 of

with type P di—˜etes under s—tisf—™tory —nd nonEs—tisf—™tory

™—ses with type P di—˜etes h—ve either hyper™holesterolemi—D

gly™emi™ ™ontrolF

hypertrigly™eridemi— or low ™on™entr—tions of rhvE™holesterol

wethodsX piftyEfour postmenop—us—l women —fter — T

‘R“F „he —˜norm—l lipid levels ™ould ˜e due to ™hroni™

week runEin diet were r—ndomized to re™eive either pl—™e˜o

hypergly™emi—D o˜esityGinsulin resist—n™e or the ™oEexisten™e of

@r˜eI™ `V7D naIQY r˜eI™ bV7D naIUA or r‚„ @r˜eI™

other se™ond—ry @eFgFD —l˜uminuri—D hypothyroidismD et™FA or

`V7D naIIY r˜eI™ bV7D naIQA for IP weeksF r‚„

prim—ry dyslipidemi—sF ƒome lipid distur˜—n™es ™—nnot ˜e

™onsisted of ™y™li™—l ™onjug—ted estrogens HFTPS mgGd—y plus

—ssessed with — simple lipid profileD sin™e severe ™h—nges in the

medrogestone S mgGd—yF et the ˜eginning —nd —t the end of

™omposition —nd su˜™l—ss distri˜ution of sever—l ™l—sses of

e—™h tre—tment period the vhv su˜™l—ss distri˜ution w—s

lipoprotein h—ve ˜een o˜served in p—tientsD even in those with

estim—ted ˜y density gr—dient ultr—™entrifug—tionF

norm—l ™holesterol —nd trigly™eride ™on™entr—tionsF „he —™™uE

‚esultsX et the ˜—seline —nd during the studyD the r˜eI™

mul—tion of the sm—ller —nd denser su˜™l—sses of vhv is one of

level w—s signifi™—ntly higher in hypergly™emi™ p—tients th—n in

those ™h—ngesF „his defe™t h—s ˜een proven to ˜e —n independent

C

the ne—rEnormogly™emi™ ™ontrols @˜—seline IHFP PFW vsF

predi™tor for ™—rdiov—s™ul—r dise—se in di—˜eti™ —nd nonEdi—˜eti™

C

TFS HFU7D €`HFHIAF „hey showed — trend for higher tot—l

popul—tions ‘S“F es — me—nD ™—ses with type P di—˜etes h—ve —

—nd vhv ™holesterolD trigly™erides —nd lower high density

pe—k di—meter signifi™—ntly sm—ller th—n do nonEdi—˜eti™

lipoproteinE™holesterol ™omp—red to ne—rEnormogly™emi™ ™onE

C C su˜je™ts @PTFP HFHV vsF PSFV HFI nmD €`HFHHIAF elsoD the

trolsD —s well —s signifi™—ntly higher trigly™eride ™on™entr—tions

proportion of vhv p—rti™les represented ˜y the sm—ll dense

in very low density lipoproteinD intermedi—te density lipoprotein

C C su˜™l—ss is higher in this ™ondition @TUFU IFU vsF SVFT PFP7D

—nd vhvEI p—rti™les —nd ™holesterol ™ontent in vhvEI —nd EP

€`HFHHSAF „he —ppe—r—n™e of sm—ll dense vhvs h—s ˜een

p—rti™lesF r‚„ de™re—sed vhvE™holesterol in ˜oth groupsF sn

rel—ted to ™h—nges in the —™tivity of the hep—ti™ lip—se —nd

the normogly™emi™ p—tients — sm—ll in™re—se in r˜eI™ w—s

™holesterol ester tr—nsfer protein indu™ed ˜y the insulin

C C

o˜served @TFS HFU vsF UFR I7D €aHFHRAF sn —ll ™—sesD r‚„

resist—n™eF elsoD the di—meter of vhv p—rti™les h—s — ™lose

did not modify the proportion of vhv represented ˜y denser

rel—tionship with gly™emi™ ™ontrolF purthermoreD the ™orre™tion

vhvsF

of hypergly™emi— is —sso™i—ted with signifi™—nt ™h—nges in vhv

gon™lusionsX r‚„ did not modify the vhv su˜™l—ss

di—meter —nd su˜st—nti—l modifi™—tions in the vhv p—rti™le

distri˜utionD even in the presen™e of moder—te ™hroni™

distri˜utionF „he effe™ts of di—˜etes on the ™on™entr—tions of

hypergly™emi— in women with type P di—˜etesF

sm—ll dense vhvs seem to ˜e gre—ter in women th—n in men ‘T“F

swet PHHIYQXIQUEIRQ „he re™ent demonstr—tion th—t st—tins or fi˜r—tes ™ould de™re—se

™—rdiov—s™ul—r mort—lity in di—˜eti™s reinfor™es the import—n™e

r‚„ a hormone repl—™ement ther—py

vhv a low density lipoprotein rhv a high density lipoprotein

swe F †ol Q F pe˜ru—ry PHHI rormone ‚epl—™ement „her—py in „ype P hi—˜etes IQU t

wexi™o±ssr—el ƒymposium

met—˜olism —re studiedF ghroni™ hypergly™emi—D gly™osyl—tion for studying —nd tre—ting the lipid distur˜—n™es in this entity

of lipoproteinsD —nd redu™ed vhv re™eptor ™on™entr—tions —re ‘UDV“F

some of the f—™tors present in women with type P di—˜etes th—t „he rel—tive risk of h—ving — ™—rdiov—s™ul—r event is gre—ter in

™—n ™ontri˜ute to the —™™umul—tion of sm—ller denser vhvsF women th—n in men with type P di—˜etes ‘W“F „he event r—te

elsoD insulin or gli˜en™l—mide m—y h—ve different effe™ts on sh—rply in™re—ses in the first few ye—rs —fter menop—useD —nd

vhv p—rti™le distri˜ution ‘PR“F sn this study the effe™ts on the estrogen defi™ien™y is the most likely re—son for the progression

vhv p—rti™le distri˜ution of the most frequently used form of of —theros™lerosis o˜served in postmenop—us—l women ‘IH“F

hormone repl—™ement ther—py were —ssessed —g—inst pl—™e˜o in ƒever—l reviews —nd met—E—n—lyses h—ve ™on™luded th—t estrogen

women with type P di—˜etes who h—d the s—me degree of glu™ose repl—™ement ther—py de™re—ses the risk of ™oron—ry he—rt dise—se

™ontrol during the entire study periodF ƒu˜je™ts were studied ˜y QS to SH7 ‘II±IQ“F roweverD the only pu˜lished prospe™tive

under s—tisf—™tory glu™ose ™ontrol @r˜eI™ `V7A —nd —fter tri—l f—iled to demonstr—te — ˜enefit in women with ™oron—ry

™hroni™ moder—te hypergly™emi— @r˜eI™ V±IP7A he—rt dise—se ‘IR“F ynly —˜out IH7 of postmenop—us—l women

in frit—in use hormone repl—™ement ther—py ‘IS“D while — gre—ter

—nd growing per™ent of women re™eive this tre—tment in the w—teri—l —nd wethods

ƒe ‘IT“F roweverD inform—tion is l—™king reg—rding the effe™t €—tients

of different r‚„ mod—lities on ™—rdiov—s™ul—r mort—lity —nd „he study group ™omprised women who were previously

™oron—ry risk f—™tors in p—tients with ™onditions su™h —s di—gnosed with type P di—˜etes —™™ording to the ehe ™riteri—

di—˜etesD whi™h is —n in™re—sed ™—rdiov—s™ul—r risk ‘IS“F —nd were SH±TS ye—rs of —geF €—rti™ip—tion in the study required

wultiple me™h—nisms ™ould ™ontri˜ute to redu™e the th—t they h—d not h—d menses for —t le—st one ye—rD h—d not

progression of v—s™ul—r lesions during estrogen ther—pyF ƒome t—ken r‚„ during the previous T monthsD —nd th—t their ˜ody

P

of the possi˜le prote™tion m—y ˜e —ttri˜uted to redu™ed vhvE m—ss index w—s PV±QS kgGm F €—tients were ™l—ssified into two

™holesterol ™on™entr—tionsD due to in™re—sed vhv re™eptor groups ˜—sed on their r˜eI™ ™on™entr—tionsF „he ––s—tisf—™tory

™on™entr—tionF sn™re—sed rhvPE™holesterol —nd de™re—sed ™ontrol group99 ™onsisted of women whose r˜eI™ w—s ˜elow

lipoprotein@—A ™on™entr—tions —re other potenti—lly prote™tive V7 ˜oth —t ˜—seline —nd —t le—st on™e during the previous ye—rF

—™tions of estrogen ‘IU“F roweverD some of its effe™ts on the lipid „he ––nonEs—tisf—™tory ™ontrol group99 in™luded women whose

profile m—y ˜e deleterious ‘IV“F istrogen de™re—ses vhv p—rti™le r˜eI™ w—s ˜etween V —nd IP7 ˜oth —t ˜—seline —nd —t le—st

sizeD while the hep—ti™ produ™tion of trigly™erides —nd the on™e during the previous ye—r ˜eforeF g—ndid—tes were ex™luded

—poprotein fE™ont—ining lipoproteins —re in™re—sedF et le—st two if they h—d type I di—˜etes mellitusD un™ontrolled hypertensionD

different groups h—ve shown th—t estrogen ther—py de™re—ses the f—sting trigly™erides —˜ove SHH mgGdlD severe ren—l dysfun™tionD

me—n pe—k di—meter of vhv p—rti™les ‘IW±PP“F „his —™tion is nephroti™ syndromeD —l™oholism @bIH drinks per weekAD —™tive

gre—ter in women with —n vhv p—ttern e @predomin—n™e in the liver dise—se or hep—ti™ enzyme elev—tion @serum —sp—rt—te or

vhv r—nge of the l—rge vhv su˜™l—ssAF „he modifi™—tion in —l—nine —minotr—nsfer—se levels bPFS times the upper limit of

vhv p—rti™le distri˜ution ™ould ˜e expl—ined either ˜y — lower norm—lAD severe venous insuffi™ien™y in the lower lim˜sD history

™on™entr—tion of the l—rger vhvs or —n in™re—sed —mount of the of venous throm˜oem˜olismD symptom—ti™ —ngin— pe™toris or

sm—ller denser vhvsF foth me™h—nisms —re possi˜ly ˜—sed on ™—rdi—™ insuffi™ien™yD o™™urren™e of — m—jor v—s™ul—r event

the estrogenEindu™ed in™re—sed expression of the vhv re™eptor within Q months prior to s™reeningD or di—gnosis of — serious or

—nd the trigly™eride enri™hment of the vhv p—rti™les th—t o™™ur ™hroni™ dise—se th—t would thre—ten the p—tient9s s—fety or life

during estrogen useF „he first me™h—nism expl—ins the lower expe™t—n™yF gon™omit—nt use of —ntiEo˜esity medi™—tionD ˜ile

—mount of l—rge vhvsD while the se™ond one ™ould ™ontri˜ute to —™id sequestr—ntsD ™y™losporinD insulin or —ny drug with

the gener—tion of sm—ll dense vhv p—rti™lesF g—mpos —nd ™oE potenti—l effe™ts on lipid met—˜olism were prohi˜ited during

workers ‘PQ“D using endogenous l—˜eling of —poprotein fD the study —nd the pre™eding Q monthsF efter enrolmentD p—tients

suggest th—t the shift in rel—tive distri˜ution of vhv p—rti™les were ex™luded if their f—sting pl—sm— glu™ose level w—s —˜ove

is ™—used ˜y preferenti—l lowering of the ™on™entr—tion of light QSH mgGdl on two different d—ys or if their f—sting trigly™eride

vhvEI p—rti™les —nd not to in™re—sed ™on™entr—tion of denser level w—s —˜ove SHH mgGdl in —ny me—surementF

vhv p—rti™lesF roweverD there is s™—nt inform—tion —˜out these „he ithi™s gommittee of snstituto x—™ion—l de gien™i—s

effe™ts for other forms of r‚„F „hese d—t— —re urgently needed wedi™—s y xutri™ion —pproved the proto™ol —nd every p—tient

sin™e only — minority of ™—ses —re tre—ted with estrogen —loneF sn provided witnessedD written informed ™onsent prior to entering

most women with — uterus — progestin is —dded to the tre—tmentY the studyF

these drugs h—d opposite effe™ts to those des™ri˜ed —˜oveF

ƒtudy design ƒtudies on the effe™ts of estrogen on lipid met—˜olism h—ve

˜een performed in he—lthy postmenop—us—l women using only „his w—s — dou˜leE˜lind pl—™e˜oE™ontrolled p—r—llelEgroup

estrogen ther—pyF roweverD in ™lini™—l pr—™ti™e this is not the studyF st in™luded — runEin R week diet period —nd — IP week

most ™ommon situ—tionF sndeedD m—ny postmenop—us—l women r—ndomized tre—tment with pl—™e˜o or hormone repl—™ement

suffer from di—˜etes or other disordersD whi™h ™ould pl—y the ther—pyF €—tients —ttended —n initi—l s™reening visit —t whi™h —n

role of ™onfounder when the effe™ts of estrogens on the lipid iso™—lori™ diet w—s pres™ri˜ed ˜y — registered dietiti—nF „his visit

IQV gFeF eguil—rEƒ—lin—s et —lF swe F †ol Q F pe˜ru—ry PHHI t

wexi™o±ssr—el ƒymposium

w—s followed ˜y — qu—lifying visit P weeks l—terF ‡ithin P weeks @f—yer v—˜or—toriesAF „ot—l serum ™holesterol —nd trigly™erides

p—tients returned for — ˜—seline visit when ˜lood s—mples were were me—sured using —n enzym—ti™ method @ƒi‚eE€eu g†

™olle™ted —nd drug tre—tment w—s —llo™—ted if the r˜eI™ met the QFQ7AF rhvE™holesterol w—s pre™ipit—ted with phosphotungsti™

CC

in™lusion ™riteri—F €—tients who h—d qu—lified were r—ndomized —™id —nd wg @g† PFS7AF vhvE™holesterol ™on™entr—tion

to re™eive m—t™hed pl—™e˜o or ™onjug—ted equine estrogen HFTPS w—s estim—ted ˜y the priedew—ld formul—F hire™t vhvE

mg for PI d—ys plus medrogestone S mg for IH d—ys every ™holesterol w—s determined ˜y ultr—™entrifug—tion @qu—ntifi™—E

monthF „he study medi™—tion w—s t—ken with ˜re—kf—stF ell tionA —t ˜—seline —nd —t the end of the tre—tment —nd in every

p—tients were s™heduled for — return visit every Q weeks until p—tient whose trigly™eride levels were —˜ove RFS mmolGvF

week IP @visits Q to UAF „hroughout the tri—l p—tients were epoprotein f ™on™entr—tion w—s me—sured ˜y —n immunoE

required to ™omply with —n iso™—lori™ diet ™onsisting of SH7 nephelometri™ methodF vhv su˜™l—ss distri˜ution w—s —ssessed

™—r˜ohydr—tesD IH7 proteinD QH7 f—t —nd QH gGd—y fi˜erF with — density gr—dient ultr—™entrifug—tion method using —

hiet—ry —dvi™e w—s given —t the initi—l visit —nd ™ompli—n™e with fe™km—n ƒ‡RH „i rotor ‘PS“F e™™ording to its density vhv

the diet w—s —ssessed —t every su˜sequent visit using — Q d—y food p—rti™les were ™l—ssified —s light @daIFHIW±IFHQS gGvA or dense

re™ordF hrug ™ompli—n™e w—s —lso me—sured —t every visitF vhv @daIFHQT±IFHTQ gGvAF „wenty —liquots @HFS mlA were

™olle™ted in every gr—dientF gholesterolD trigly™erides —nd

—poprotein f ™on™entr—tions were me—sured in e—™h —liquot ‘PT“F iffi™—™y p—r—meters

„he prim—ry effi™—™y ev—lu—tion w—s ˜—sed on ™h—nge in vhv

p—rti™le distri˜ution o˜served ˜etween ˜—seline —nd the end of ƒt—tisti™—l —n—lysis

—™tive tre—tmentF „he ˜—seline v—lue w—s o˜t—ined —fter the R ƒt—tisti™—l —n—lysis w—s performed with the ƒt—tgr—phi™s

week le—d during the diet periodF ƒe™ond—ry effi™—™y ev—lu—tions progr—m version UFIF hifferen™es ˜etween groups were ev—lE

were ˜—sed on the ™h—nge from ˜—seline to week IP for tot—l u—ted using the twoEt—iled p—ired t testF ell testing w—s two sided

™holesterolD trigly™eridesD rhvE™holesterolD vhvE™holesterol —nd ™ondu™ted —t — S7 level of signifi™—n™eF „he s—mple size w—s

—nd r˜eI™ ™on™entr—tionsF ˜—sed on the —ssumption th—t — ™h—nge of PH7 or gre—ter in the

proportion represented ˜y the sm—ll dense vhvs would ˜e

™onsidered —s ™lini™—lly signifi™—ntF ƒ—fety ev—lu—tion

fefore entering the ˜—seline ph—seD — ™omplete physi™—l

ex—min—tion —nd ™lini™—l l—˜or—tory ev—lu—tion were performedF ‚esults

„he l—˜or—tory ev—lu—tion in™luded — ˜lood ™ountD pregn—n™y

„he study group ™omprised SR postmenop—us—l women with

testD urine ex—min—tionD ™re—tine kin—se levelsD liver fun™tion

type P di—˜etesF „wentyEfour p—tients h—d — r˜eI™ `V7

tests —nd — gly™emi™ profile @f—sting pl—sm— glu™ose —nd

during —nd —t the ˜eginning of the studyY the rem—ining QH h—d —

r˜eI™AF „hese tests were repe—ted —t the end of the studyF et

r˜eI™ bV7F efter — R week diet runEin period the p—tients

e—™h visit the liver fun™tion tests —nd gly™emi™ profile were

were r—ndomized to re™eive either pl—™e˜o @r˜eI™ `VD naIQY

me—suredF €—tients were ex™luded from the study if they

r˜eI™ bVD naIUA or r‚„ @r˜eI™ `VD naIIY r˜eI™ bVD

developed severe hypergly™emi— @bQSH mgGdlA or —ny other

naIQA for IP weeksF xo signifi™—nt ™h—nge in fwsD diet or

signifi™—nt devi—tion from s—fety testsF en ev„ or eƒ„

physi™—l —™tivity w—s o˜served in —ny of the groups during the

™on™entr—tion three times —˜ove the upper limit of norm—l on

studyF

two ™onse™utive me—surements I week —p—rt @CQ d—ysA w—s

„he ™lini™—l ™h—r—™teristi™s of the women in™luded in the

™onsidered —s indi™—tion for ex™lusion from the studyF yther

study —re shown in „—˜le IF es expe™tedD hypergly™emi™ p—tients

re—sons for dismiss—l were l—™k of ™ompli—n™e to the drug or

h—d higher levels of pl—sm— trigly™erides —nd lower ™on™entr—E

dietF

tions of rhvE™holesterolD ˜ut these differen™e did not —™hieve

st—tisti™—l signifi™—n™eF „hese differen™es were gre—ter in the

v—˜or—tory —n—lyses

results from the density gr—dient ultr—™entifug—tionF ryperglyE

„he l—˜or—tory of the hep—rtment of indo™rinology —nd

™emi™ ™—ses h—d signifi™—ntly gre—ter ™on™entr—tions of ™holesE

wet—˜olism —t our institute performed —ll lipid —nd ™lini™—l

terol —nd trigly™erides in the †vhvGshvD light —nd dense vhv

l—˜or—tory me—surements using st—nd—rdized pro™eduresF „his

p—rti™lesF

l—˜or—tory is ™ertified for st—nd—rdiz—tion of tests ˜y the

„he effe™ts of pl—™e˜o —nd hormone repl—™ement ther—py in

ixtern—l gomp—r—tive iv—lu—tion of v—˜or—tories €rogr—m of

su˜je™ts with r˜eI™ `V7 —re shown in „—˜le PF es expe™tedD

the gollege of emeri™—n €—thologistsF flood s—mples were

no ™h—nge in weightD glu™oseD r˜eI™ or lipid levels resulted

t—ken —fter —n overnight f—st @W±IP hoursAF ell l—˜or—tory

from pl—™e˜o tre—tmentF r‚„ ™—used — sm—ll ˜ut st—tisti™—lly

—n—lyses were performed with ™ommer™i—lly —v—il—˜le st—nd—rE

C C

signifi™—nt in™re—se in r˜eI™ levels @TFT IFI vsF UFS IFI7D

dized methodsF qlu™ose w—s me—sured using the glu™ose oxid—se

€`HFHSAD ˜ut no ™h—nge in pl—sm— glu™ose w—s dete™ted in the

methodD r˜eI™ using l—tex immuno—gglutin—tion inhi˜ition

ev„ a —l—nine —minotr—nsfer—se fws a ˜ody m—ss index

eƒ„ a —sp—rt—te —minotr—nsfer—se †vhvGshv a very lowGintermedi—te density lipoprotein

swe F †ol Q F pe˜ru—ry PHHI rormone ‚epl—™ement „her—py in „ype P hi—˜etes IQW t

wexi™o±ssr—el ƒymposium

„—˜le IF gh—r—™teristi™s —nd lipid profile of the su˜je™ts —t ˜—seline „—˜le PF iffe™ts of the estrogenGprogestin ther—py in women with

r˜eI™`V7

†—ri—˜le r˜eI™ `V7 r˜eI™ bV7 €

†—ri—˜le €l—™e˜o istrogenG € @naPSA @naQHA

@naIQA progestin ege @yrA STCPFW SRCSFV xƒ

@naIIA hi—˜etes dur—tion @yrA RFQCHFWI SFWCQFU xƒ

P

r˜eI™ ˜—s—l @7A TFICIFP TFTCIFI xƒ A PWFTCRFS QHFRCRFI xƒ fws @kgGm

r˜eI™ fin—l @7A TFQCHFW UFSCIB xƒ r˜eI™ @7A IHFQCPFS TFICIFP `HFHHI

vhvE™holesterol ˜—s—l @mgGdlA IQTCQQ ISHCRI xƒ p—sting pl—sm— glu™ose IITCRR IWICTT `HFHHI

vhvE™holesterol fin—l @mgGdlA IQUCPU IPRCQVB xƒ @mgGdlA

„rigly™erides ˜—s—l @mgGdlA ISUCUQ IQUCSI xƒ gholesterol @mgGdlA PPPCQW PPTCQV xƒ

„rigly™erides fin—l @mgGdlA IRSCSH ISTCTR xƒ vhvEg @mgGdlA IRPCQU IRTCQI xƒ

rhvE™holesterol ˜—s—l @mgGdlA SHFUCIQ SIFICIQ xƒ rhvEg @mgGdlA SICIQ RTCIH xƒ

rhvE™holesterol fin—l @mgGdlA RWFWCIH SRFVCII xƒ „rigly™erides @mgGdlA IRVCTR IVICIIU xƒ

hensity gr—dient f—seline pin—l hensity gr—dient ultr—™entrifug—tion

ultr—™entrifug—tion †vhvGshv ™holesterol TSCPU WWCPI `HFHS

istrogenGprogestin group @mgGdlA

†vhvEshv ™holesterol TSCPU VWCSH xƒ vhvIE™holesterol @mgGdlA ISTCQU PPUCQH `HFHI

vhvEI ™holesterol IUHCVR IIICSI HFHS vhvPE™holesterol @mgGdlA WSCQR IIPCPT `HFHS

vhvEP ™holesterol WICQR TSCIW xƒ †vhvGshv trigly™erides IHSCSS ITPCUP `HFHS

†vhvEshv trigly™erides IIUCSH IPTCRR xƒ @mgGdlA

vhvEI trigly™erides QVCIU UTCQU `HFHI vhvEI trigly™erides @mgGdlA RPCPP UQCPI `HFHS

vhvEP trigly™erides IWCIR QWCPH HFHP vhvEP trigly™erides @mgGdlA PRCPH PUCIP `HFHS

7 vhv p—rti™les represented ˜y TTCPW TQCIV xƒ

h—t— —re expressed —s me—nCƒh

light vh

„he ™on™entr—tions o˜t—ined from the density gr—dient ultr—™entrifug—tion

™orrespond to the —re— under the ™urve in the ™orresponding density r—ngeF „he

€l—™e˜o group gr—dient used in this report is not useful to sep—r—te the †vhv —nd shv p—rti™lesY

†vhvEshv ™holesterol UICRS VICQT xƒ these results —re presented —s — single density r—ngeF

vhvEI ™holesterol IQTCUQ IWSCVR xƒ

vhvEP ™holesterol IHPCPP VWCII xƒ

f—sting s—mplesF istrogenGprogestin ther—py signifi™—ntly reE

†vhvEshv trigly™erides WWCUW IITCTU xƒ

C C du™ed vhvE™holesterol ™on™entr—tions @ISH RI vsF IPR QVD vhvEI trigly™erides SRCQP SRCIV xƒ

€`HFHIAF ƒlightly higher ™on™entr—tions of trigly™erides —nd vhvEP trigly™erides QICPW QICIU xƒ

7 vhv p—rti™les represented ˜y SWCPR TUCIT xƒ rhvE™holesterol ™on™entr—tions were o˜served —t the end of

light vhv tre—tmentD ˜ut these differen™es were not st—tisti™—lly signifi™—ntF

„he me—n per™ent of ™h—nge in trigly™eride ™on™entr—tion w—s

h—t— —re expressed —s me—nCƒhF

IU7 @r—nge H±RI7AF et the end of tre—tment only one of the II B € ` HFHS ˜etween ˜—seline —nd fin—l me—surementsF

„he ™on™entr—tions o˜t—ined from the density gr—dient ultr—™entrifug—tion r‚„Etre—ted p—tients h—d f—sting trigly™erides —˜ove PHH mgGdlF

™orrespond to the —re— under the ™urve in the ™orresponding density r—ngeF „he

„hese lipid ™h—nges were —lso o˜served in the results from the

gr—dient used in this report is not useful to sep—r—te the †vhv —nd shv p—rti™lesY

density gr—dient ultr—™entrifug—tionF en in™re—sed trigly™eride

these results —re presented —s — single density r—ngeF

™ontent w—s found in —ll —poprotein fE™ont—ining lipoproteinsF

„his ™h—nge w—s st—tisti™—lly signifi™—nt for ˜oth vhv

su˜™l—ssesF sn —dditionD — de™re—sed ™holesterol ™ontent in the signifi™—ntly gre—terF ƒignifi™—ntly higher ™on™entr—tions of

vhv su˜™l—sses w—s o˜servedF „his ™h—nge w—s m—rkedly trigly™eride ™on™entr—tions were o˜served —t the end of

gre—ter for the light vhvsF „he proportion of vhv @—ssessed ˜y tre—tmentY this ™h—nge w—s m—rkedly gre—ter th—n in the ™—ses

the —re— ˜eyond the ™urve of the —poprotein f ™on™entr—tion on with r˜eI™ `V7 @€`HFHSAF yne wom—n h—d f—sting

the vhv r—ngeA represented ˜y the light —nd dense vhvs w—s

trigly™erides —˜ove IDHHH mgGdl —fter IP weeks of tre—tmentD

not modified ˜y the tre—tmentF

˜ut no symptoms were rel—ted to this —˜norm—lityF rer ˜—seline

v—lue w—s RPU mgGdl @the highest v—lue of the study groupAF et

„he effe™ts of pl—™e˜o —nd hormone repl—™ement ther—py in

the end of the tre—tmentD S of the IQ women who re™eived r‚„ p—tients with r˜eI™ bV7 —re shown in „—˜le QF €—tients

h—d trigly™erides —˜ove PHH mgGdlF „he me—n per™ent ™h—nge in rem—ined hypergly™emi™ during the whole studyD —s shown ˜y

trigly™eride ™on™entr—tion w—s RR7 @r—nge H±IIP7AF ƒlightly the l—™k of modifi™—tion ˜etween the ˜—seline —nd fin—l r˜eI™

higher rhvE™holesterol ™omp—red to ˜—seline w—s found —t the ™on™entr—tionsF xo ™h—nge in weightD glu™oseD r˜eI™ or lipid

end of the tre—tmentD while estrogenGprogestin ther—py sigE levels resulted from pl—™e˜o tre—tmentF nlike the former

C nifi™—ntly redu™ed vhvE™holesterol ™on™entr—tions @ISH RI vsF groupD r‚„ h—d no imp—™t on either the r˜eI™ or f—sting

C IPR QVD €`HFHIAF „hese ™h—nges were —lso o˜served in the pl—sm— glu™ose ™on™entr—tionsF ‚eg—rding the lipid responses to

the tre—tmentD the ™h—nges followed the s—me trend ˜ut were results of the density gr—dient ultr—™entrifug—tionF en in™re—sed

IRH gFeF eguil—rEƒ—lin—s et —lF swe F †ol Q F pe˜ru—ry PHHI t

wexi™o±ssr—el ƒymposium

„—˜le QF iffe™ts of the estrogenGprogestin ther—py in the hyperglyE ther—pyD w—s more ™ommon —nd severe in the presen™e of —

™emi™ p—tients r˜eI™ —˜ove V7F we—n trigly™eride ™on™entr—tion —t the end

of r‚„ w—s signifi™—ntly higher in the hypergly™emi™ group

†—ri—˜le €l—™e˜o istrogenG €

C C

@PSI PRR vsF IST TR mgGdlD €`HFHIAF purthermoreD in the

@naIUA progestin

group of women with r˜eI™ —˜ove V7D ™hylomi™ronemi— w—s @naIQA

pre™ipit—ted in one p—tient —nd QV7 h—d f—sting trigly™erides r˜eI™ ˜—s—l @7A IHFPCPFR IHFSCPFU xƒ

—˜ove PHH mgGdl —fter IP weeks of r‚„F sn ™ontr—stD only one r˜eI™ fin—l @7A IHCPFS HFTCQFS xƒ

vhvE™holesterol ˜—s—l @mgGdlA IRSCPW ISHCQT xƒ wom—n with r˜eI™ ˜elow V7 h—d —˜norm—lly high ™on™enE

vhvE™holesterol fin—l @mgGdlA IRHCQV IPSCRSB xƒ tr—tions of trigly™erides —t the end of the tre—tmentF yther effe™ts

„rigly™erides ˜—s—l @mgGdlA IUTCVW IVUCISI xƒ

on the lipid profile usu—lly o˜served during r‚„ @eFgFD lower

„rigly™erides fin—l @mgGdlA ITPCVQ PSICPRRB xƒ

vhvE™holesterol —nd higher rhvE™holesterolA seem not to h—ve

rhvE™holesterol ˜—s—l @mgGdlA RUCW RSFICII xƒ

˜een —ffe™ted ˜y the r˜eI™ ™on™entr—tionsF „he higher

rhvE™holesterol fin—l @mgGdlA SICVRVCWxƒ

trigly™eride ™on™entr—tions o˜served —t the end of r‚„ in the

hypergly™emi™ women ™ould ˜e expl—ined ˜y either — higher hensity gr—dient f—seline pin—l

˜—seline v—lue or — gre—ter hypertrigly™eridemi™ response to ultr—™entrifug—tion

estrogens during ™hroni™ hypergly™emi—F foth me™h—nisms seem istrogenGprogestin group

†vhvEshv ™holesterol WWCSW VICSR xƒ to h—ve pl—yed — role in women with r˜eI™ bV7D ˜—sed on the

vhvEI ™holesterol PPUCVU IVRCUV HFHS higher ˜—seline v—lues —nd the gre—ter per™ent ™h—nge @IU vsF

vhvEP ™holesterol IIPCTW IHRCTI xƒ

RR7D €`HFHSA during r‚„F „hese d—t— suggest th—t glu™ose

†vhvEshv trigly™erides ITPCWV PQTCIWP HFHI

™ontrol must ˜e —ssessed ˜efore pres™ri˜ing r‚„ to women

vhvEI trigly™erides UQCRQ USCRT xƒ

with type P di—˜etesF sn the presen™e of r˜eI™ —˜ove V7 —nd

vhvEP trigly™erides PUCIS RPCPP HFHS

trigly™erides —˜ove PHH mgGdlD the risk of h—ving ™hylomi™roE

7 vhv p—rti™les represented ˜y TTFVCIT TQCIU xƒ

nemi— —nd possi˜le rel—ted ™ompli™—tions @p—n™re—titisA might ˜e light vhv

higher th—n in women under s—tisf—™tory glu™ose ™ontrolF „o the

˜est of our knowledgeD no prospe™tive study h—s reported this €l—™e˜o group

†vhvEshv ™holesterol WRCRU USCRI xƒ o˜serv—tionF „he higher trigly™eride response to r‚„ w—s

vhvEI ™holesterol PPICTS PIICUH xƒ reported in — ™rossEse™tion—l study —ssessing the effe™ts of r‚„

vhvEP ™holesterol IIRCTH IIWCSS xƒ

in women with —nd without di—˜etesD ˜ut the inter—™tion with

†vhvEshv trigly™erides IWPCIIU ITVCIPH xƒ

glu™ose ™ontrol w—s not me—sured ‘PU“F eddition—l studies

vhvEI trigly™erides SQCQI TICQV xƒ

—ssessing the s—fety of r‚„ in hypergly™emi™ women —re

vhvEP trigly™erides QCPI QICPH xƒ

requiredF

7 vhv p—rti™les represented ˜y TTCIT TRCIT xƒ

yur d—t— —re in —™™ord—n™e with the ™omplex effe™ts of light vhv

estrogen —nd progestins on the lipoprotein met—˜olismF r‚„

h—t— —re expressed —s me—nCƒhF

resulted in trigly™eride enri™hment of —lmost every —poprotein

B €`HFHS ˜etween ˜—seline —nd fin—l me—surementsF

fE™ont—ining lipoproteinD —s shown in „—˜les P —nd QF „hese

„he ™on™entr—tions o˜t—ined from the density gr—dient ultr—™entrifug—tion

results ™on™ur with the reports ˜y g—mpos ‘PQDPV“ who

™orrespond to the —re— under the ™urve in the ™orresponding density r—ngeF „he

demonstr—ted th—t estrogen ther—py in™re—ses the hep—ti™ gr—dient used in this report is not useful to sep—r—te the †vhv —nd shv

produ™tion of trigly™erides —nd —poprotein f ˜y SH7F „hese p—rti™lesY these results —re presented —s — single density r—ngeF

™h—nges —re ™ounter˜—l—n™ed ˜y —n in™re—sed expression of the

vhv re™eptorD —s this me™h—nism ˜lunts —ny —™™umul—tion of

trigly™eride ™ontent of —ll —poprotein fE™ont—ining lipoproteins —poprotein fE™ont—ining p—rti™les ™—used ˜y the hep—ti™ overE

w—s foundD whi™h w—s st—tisti™—lly signifi™—nt for the dense vhv produ™tion of —poprotein fF sn f—™tD the overexpression of the

su˜™l—ssF elsoD there w—s — de™re—sed ™holesterol ™ontent of the vhv re™eptor de™re—sed the vhvE™holesterol ™on™entr—tions

vhv su˜™l—ssesD whi™h w—s m—rkedly gre—ter for the light o˜served in this studyF roweverD —s dis™ussed in the following

vhvsF „he proportion of vhv @—ssessed ˜y the —re— ˜eyond the p—r—gr—phsD the overprodu™tion of trigly™erides m—y ™h—nge the

™urve of the —poprotein f ™on™entr—tion on the vhv r—ngeA ™omposition —nd met—˜olism of the †vhvD shv —nd vhv

represented ˜y the light —nd dense vhvs w—s not modified ˜y p—rti™lesF

the tre—tmentF

r‚„ did not modify the vhv p—rti™le distri˜utionD even in

the presen™e of ™hroni™ hypergly™emi—F „his m—y ˜e the result of

the ™om˜in—tion of met—˜oli™ —˜norm—lities with opposite his™ussion

™onsequen™esF „rigly™eride enri™hment of the vhv p—rti™les

indu™ed ˜y r‚„ suggests th—t the produ™tion of the sm—ll dense „he d—t— reported here ™le—rly show th—t the effe™ts of r‚„ on

vhv p—rti™les is in™re—sedD ˜—sed on previous reports th—t the lipid profile —re modul—ted ˜y the presen™e of ™hroni™

trigly™eride enri™hment of the vhv p—rti™le is the m—in hypergly™emi— in women with type P di—˜etesF rypertrigly™erE

determin—nt for the form—tion of the sm—ll dense vhv ‘PW“F idemi—D the most trou˜lesome —dverse effe™t of estrogen

swe F †ol Q F pe˜ru—ry PHHI rormone ‚epl—™ement „her—py in „ype P hi—˜etes IRI t

wexi™o±ssr—el ƒymposium

effe™ts on lipoprotein met—˜olismF „he trigly™eride enri™hment roweverD this —˜norm—lity m—y ˜e ™ounter˜—l—n™ed ˜y the

of —poprotein fE™ont—ining lipoprotein plus the prothrom˜oti™ overexpression of the vhv re™eptorD whi™h redu™es the

—nd proEinfl—m—tory —™tions ‘QS“ of r‚„ m—y help to expl—in ™on™entr—tion of —ll vhv p—rti™lesF „he ™le—r—n™e of the light

the l—™k of ˜enefit o˜served in the re—rt —nd istrogenG€rogestin vhv ˜y the vhv re™eptor is signifi™—ntly gre—terD ˜ut this

‚epl—™ement ƒtudy @ri‚ƒAF yur d—t— demonstr—te th—t some ™h—nge indire™tly redu™es the —mount of the dense vhv sin™e

of the —dverse effe™ts of r‚„ m—y inter—™t with ™hroni™ the light vhv is the pre™ursor for the produ™tion of the sm—ll

hypergly™emi—D m—king it more frequent —nd severeF „his report dense p—rti™le ‘QH“F „he ™om˜in—tion of these phenomen— results

reinfor™es the import—n™e of —ssessing the s—fety —nd effi™—™y of in de™re—sed ™on™entr—tion of ˜oth vhv su˜™l—sses —nd —

r‚„ in women with type P di—˜etes —nd the urgent need for simil—r proportion of the light —nd dense su˜™l—ssesF „hese

—ddition—l studies in this su˜set of postmenop—us—l womenF postul—ted me™h—nisms —re in —™™ord—n™e with the signifi™—nt

redu™tion of vhvEI ™holesterol —nd the sm—ller ™h—nge in vhvE

P ™holesterol found in the density gr—dient ultr—™entrifug—tionD

‚eferen™es

—nd the lower vhv ™holesterol o˜served during r‚„F sf these

IF u—set— tD ƒk—f—r hD ‚—m tD t—™o˜er ƒD ƒowers tF g—rdiov—s™ul—r dise—se in ™on™lusions —re trueD we postul—te th—t the ™oEexisten™e of —ny

the di—˜eti™ wom—nF t glin indo™rinol wet—˜ IWWWYVRXIVQS±VF other disorder th—t downEregul—tes the vhv re™eptor @iFeFD

PF g—mpos rD w™x—m—r— t‚D ‡ilson €‡D yrdov—s twD ƒ™h—efer itF

hypothyroidismD nephroti™ syndromeA m—y disrupt this equiliE

hifferen™es in low density lipoprotein su˜fr—™tions —nd —polipoproteins in

˜rium ‘QI“D resulting in the —™™umul—tion of —ll —poprotein fE

premenop—us—l —nd postmenop—us—l womenF t glin indo™rinol wet—˜

™ont—ining p—rti™les during r‚„F „his sequen™e of events m—y IWVVYTUXQH±RF

expl—in the higher trigly™eride response o˜served during r‚„ in QF gh—it eD fierm—n iF €—thogenesis of m—™rov—s™ul—r dise—se in di—˜etesF snX

u—hn g‚D ‡eir qgD edsF toslin9s hi—˜etes wellitusF IQth ednF €hil—delphi—X hypergly™emi™ womenD whi™h is due to the —dverse effe™ts of

ve— pe˜igerD IWWRXTRV±TRF hypergly™emi— on the fun™tion of the vhv re™eptorF es — resultD

RF emeri™—n hi—˜etes esso™i—tionF w—n—gement of dyslipidemi— in —dults with

trigly™erideEri™h p—rti™les —re —™™umul—ted in pl—sm—F roweverD

di—˜etesF hi—˜etes g—re PHHHYPQ@ƒuppl IAXƒSU±THF

this expl—n—tion does not fit the l—™k of modifi™—tion of the

SF eustin weD rok—nson tiD frunzell thF gh—r—™teriz—tion of low density

vhv p—ttern during r‚„ —nd ™hroni™ hypergly™emi—F eddiE lipoproteins su˜™l—ssesX methodologi™ —ppro—™hes —nd ™lini™—l relev—n™eF gurr

tion—l rese—r™hD in™luding kineti™ studies using endogenous ypin vipidol IWWRYSXQWS±RHQF

TF r—ffner ƒwF qre—ter effe™t of di—˜etes on vhv size in women th—n in menF l—˜eling of —poprotein fD is ne™ess—ry to underst—nd the

hi—˜etes g—re IWWRYIUXIITR±UIF

™omplex inter—™tion ˜etween the effe™ts of r‚„ —nd ™hroni™

UF floomfield rD ‚o˜ins ƒD gollins hD pye gD enderson tD il—m wD p——s pD

hypergly™emi—F

vin—res iD ƒ™h—efer iD ƒ™he™tm—n qD ‡ilt „D ‡ittes t for the †eter—ns eff—irs

„he d—t— presented here ™onfirm th—t signifi™—nt —˜norm—lE righ hensity vipoprotein gholesterol sntervention ƒtudy qroupF qemfiE

ities in the ™omposition of the —polipoprotein fE™ont—ining ˜rozil for the se™ond—ry prevention of ™oron—ry he—rt dise—se in men with low

levels of high density lipoprotein ™holesterolF x ingl t wed IWWWYQRIXRIH±IVF lipoprotein m—y exist in women with type P di—˜etesD even those

VF qold˜erg ‚D wellies wD ƒ—™ks pD woye vD row—rd fD t—mes ‡D h—vis fD with — ––norm—l99 lipid profileF „he ˜—seline lipid profile of the

gole „D €feffer wD fr—unw—ld i for the ge‚i snvestig—torsF g—rdiov—s™ul—r

women with r˜eI™ —˜ove or ˜elow V7 were not st—tisti™—lly

events —nd their redu™tion with pr—v—st—tin in di—˜eti™ —nd glu™ose intoler—nt

differentD —lthough higher trigly™erides —nd lower rhvE

myo™—rdi—l inf—r™tion survivors with —ver—ge ™holesterol levelsF gir™ul—tion

™holesterol were found in the hypergly™emi™ groupF roweverD IWWVYWVXPSIQ±IWF

when the results of the density gr—dient ultr—™entrifug—tion were WF uuller vrD weil—hn ixF ‚isk f—™tors for ™—rdiov—s™ul—r dise—se —mong

womenF gurr ypin vipidol IWWTYUXPHQ±VF ™omp—red l—rge differen™es were found ˜etween the two groupsF

IHF ƒeed wD grook hF €ost menop—us—l hormone repl—™ement ther—pyD ™oron—ry „hese d—t— suggest th—t the f—sting lipid profile m—y underE

he—rt dise—se —nd pl—sm— lipoproteinsF gurr ypin vipidol IWWRYSXRV±SVF estim—te the lipoprotein —˜norm—lities in su˜je™ts with type P

IIF €s—ty fwD re™k˜ert ƒ‚D etkins hF e review of the —sso™i—tion of estrogens

di—˜etes ‘QP“F

—nd progestins with ™—rdiov—s™ul—r dise—se in postmenop—us—l womenF er™h

e sm—ll ˜ut st—tisti™—lly signifi™—nt in™re—se in r˜eI™

sntern wed IWWQYISQXIRPI±UF

™on™entr—tions w—s found —fter IP weeks of r‚„ in women IPF ƒt—mpfer wtD gol xF €ostmenop—us—l estrogen ther—py —nd ™—rdiov—s™ul—r

dise—seF „en ye—r followEup from the xurses re—lth ƒtudyF x ingl t wed with ˜—seline levels ˜elow V7F „his deleterious ™h—nge m—y ˜e

IWWIYQPSXUST±TPF expl—ined ˜y the known effe™ts of the progestins on the insulin

IQF wos™— vF „he role of hormone repl—™ement ther—py in the prevention of

—™tion ‘QQ“F „his modifi™—tion on insulin sensitivity does not

postmenop—us—l he—rt dise—seF er™h sntern wed PHHHYITHXPPTQ±UPF

seem to h—ve — ™lini™—l effe™t in su˜je™ts with r˜eI™ —˜ove V7F

IRF rulley ƒD qr—dy hD fush „F ‚—ndomized tri—l of estrogen plus progestin for

nfortun—telyD the v—st m—jority of studies ev—lu—ting the effe™ts

se™ond—ry prevention of ™oron—ry he—rt dise—se in postmenop—us—l womenF

of r‚„ on glu™ose ™ontrol h—ve ˜een done in nonEdi—˜eti™ tewe IWWVYPVHXTHS±IQF

womenF fruss—rd et —lF ‘QR“ reported th—t shortEterm estrogen ISF hunne pidelm— €D r—rris €D ue—ne vD tenkins hD ‡rigt ehF rormone

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