IBIMA Publishing Journal of Research and Practice in Dentistry http://www.ibimapublishing.com/journals/DEN /dent.html !ol.

"#$% &"#$%'( )rticle *D +,-++#( $# pages D.*: $#.,$/$/"#$%.+,-++#

Research Article

Proinflammatory Cytokines in the Saliva, Gingival Crevicular Fluid and Serum of Diabetic Patients with Periodontal Disease
Fawad Javed1 and Asma Ahmed2
Research Chair for Growth Factors and Bone Regeneration, 3D Imaging and Biomechanical Laboratory, College of A lied !edical "ciences, #ing "a$d %ni&ersity, Riyadh, "a$di Arabia
' 1

Aachen dental Laser Centre, R()* Aachen %ni&ersity, Aachen, Germany

Corres ondence sho$ld be addressed to+ Fawad ,a&ed- faw.a&/gmail0com Recei&ed '1 !ay '113- Acce ted '3 ,$ne '113- 2$blished '3 A$g$st '113 Academic 4ditor+ 5$rcan B$d$neli Co yright 6 '113 Fawad ,a&ed and Asma Ahmed0 Distrib$ted $nder Creati&e Commons CC7B8 301 Abstract Periodontal disease (P') is a %om4li%ation of dia(etes mellit&s (or dia(etes), +ario&s 4roinflammatory %yto!ines are e54ressed in the saliva, $in$ival %revi%&lar fl&id (# F) and ser&m of dia(eti% 4atients with P', 6he aim of this st&dy was to review the 4roinflammatory %yto!inees that are e54ressed in the saliva, # F and ser&m of dia(eti% 4atients with P', 6he addressed fo%&sed 7&estion was 89hi%h 4roinflammatory %yto!ines are e54ressed in the saliva, # F and ser&m of dia(eti% 4atients with P':8 'ata(ases were e54lored from 1..1 &4 to and in%l&din$ ;ay 2013 &sin$ vario&s %om(inations of !eywords, Arti%les 4&(lished only in <n$lish were in%l&ded, =istori% reviews, &n4&(lished data, and review arti%les were e5%l&ded, >evels of interle&!in (->)?0 are hi$her in the saliva, ser&m and # F of dia(eti% 4atients with P' %om4ared to healthy %ontrols, ->?1@ and t&mor ne%rosis fa%tor?al4ha (6AF?B) are hi$her in the ser&m and # F of dia(eti% 4atients in P' %om4ared to healthy %ontrols, 9ea! eviden%e also # F and ser&m s&$$ested that resistin and visfatin are also dysre$&lated in dia(eti% 4atients with P' %om4ared to %ontrols, *aised levels of 4roinflammatory %yto!ines (in%l&din$ ->?1@, ->?0 and 6AF?B) in the saliva, ser&m and # F of dia(eti% 4atients with P' may (e a val&a(le tool in the early dete%tion of P', <levated %on%entrations of 4roinflammatory %yto!ines in the saliva, ser&m and3or # F may also (e indi%ative of 8latent8 dia(etes in &ndia$nosed individ&als, Keywords: mellit&s, ntroduction Periodontal disease (P') Ceo4ardiDes the s&44ortin$ str&%t&res of teeth in%l&din$ 4eriodontal li$ament and alveolar (one), P' is %a&sed (y an im(alan%e (etween 4eriodontal 4atho$ens and host res4onses
_____________ Cite this Article as: Fawad Javed and Asma Ahmed (2013), Proinflammatory yto!ines in the "aliva, #in$ival revi%&lar Fl&id and "er&m of 'ia(eti% Patients with Periodontal 'isease,) Jo&rnal of *esear%h and Pra%ti%e in 'entistry, +ol, 2013 (2013), Arti%le -' ./0..0, '1-: 10,/12132013,./0..0

yto!ine, 4eriodontal disease, saliva, ser&m, $in$ival %revi%&lar fl&id, dia(etes

( osta et al,, 2010), -f left &ntreated, P' may %a&se destr&%tion of these s&44ortin$ str&%t&res and &ltimately %a&se tooth loss ( osta et al, 2010E &tando et al,, 2003E #omes et al,, 2000), "i$nifi%ant ris! fa%tors for P' are %hroni% hy4er$ly%emi% %onditions s&%h as 4oorly?%ontrolled ty4e 2

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

dia(etes mellit&s (62';) and 4redia(etes (Fandyo4adhyay et al,, 2010E Javed et al,, 2013aE Javed et al,, 200.E Javed et al,, 2002E Javed and *omanos 200.E Javed et al,, 2013(), Persistent hy4er$ly%emia mod&lates 4eriodontal tiss&e destr&%tion (y alterin$ the f&n%tion of 4olymor4hon&%lear (P;A) le&!o%ytes, %olla$en and $ly%osamino$ly%an synthesis, formation of advan%ed $ly%ation end 4rod&%ts (A#<s), and dere$&latin$ %yto!ine 4rod&%tion ( hen et al,, 2010E 'a$ et al,, 200.E Gardesler et al,, 2010E >alla et al,, 2002E 1H onnell et al,, 200I), yto!ines are water?sol&(le $ly%o4roteins se%reted (y hemato4oieti% and non? hemato4oieti% %ells in res4onse to infe%tion, 6heir 4rimary f&n%tion is inter%ell&lar si$nalin$ (=olloway et al,, 2002), An inflammatory %yto!ine may (e des%ri(ed as a %yto!ine whi%h is ind&%ed d&rin$ an inflammatory res4onse and is asso%iated with the onset and3or 4ro$ression of the ins&lt, "o far, interle&!in (->)?l al4ha (B) ->? (eta (@) ->?0, ->?I, and t&mor ne%rosis fa%tor (6AF)? al4ha (B) have (een %ate$oriDed as inflammatory %yto!ines, "in%e alveolar (one resor4tion is a %lassi%al feat&re of P', st&dies have 4aid 4arti%&lar attention to the roles of inflammatory %yto!ines in saliva ( osta et al,, 2010E &tando et al,, 2003E #omes et al,, 2000), $in$ival %revi%&lar fl&id (# F) ( ole et al,, 200IE orrea et al,, 200IE <n$e(retson et al,, 2000E FitDsimmons et al,, 2010E Gardesler et al,, 200IE Aarei!a et al,, 2002E Aavarro? "an%heD et al,, 2002E "alvi et al,, 1..IE "alvi et al,, 2010E "alvi et al,, 1..2() and ser&m ( hen et al,, 2010E 'a$ et al,, 200.E <n$e(retson et al,, 2002E -oannido& et al,, 2000E Gardesler et al,, 2010E >alla et al,, 2000E Aishim&ra et al,, 2000E 1H onnell et al,, 200IE Pradee4 et al,, 2010) of individ&als with P', "im&ltaneo&sly, the in%reased 4revalen%e of P' in 4atients with 4oorly? %ontrolled dia(etes may (e e54lained (y the role of 6AF?B whi%h 4lays a 4redominant role in ind&%in$ ins&lin resistan%e in o(ese s&(Ce%ts (Aishim&ra and ;&rayama 2001), -t has (een hy4othesiDed that 6AF?B levels in the %ir%&lation of dia(eti% s&(Ce%ts are infl&en%ed (y 4eriodontal infe%tion and inflammation (Aishim&ra and ;&rayama
_______________

2001), 6herefore, 4eriodontal treatment may im4rove the meta(oli% %ontrol of dia(etes via im4roved ins&lin sensitivity (y red&%in$ the 4eri4heral 6AF?B %on%entration, Altho&$h se4arate st&dies have investi$ated the %yto!ine e54ressions in saliva, # F and ser&m in dia(eti% 4atients with P'E we o(served that a review arti%le that wo&ld 4rovide an overview of the 4otent 4roinflammatory %yto!ines e54ressed in the saliva, # F and ser&m of dia(eti% 4atients with P' is not yet availa(le, -n this %onte5t, the aim of the 4resent st&dy was to %om4rehensively review the 4otent 4roinflammatory %yto!ines in saliva, $in$ival %revi%&lar fl&id and ser&m of dia(eti% 4atients with P', !aterials and methods Focused Question 6he addressed fo%&sed 7&estion was 89hi%h 4roinflammatory %yto!ines are e54ressed in the saliva, # F and ser&m of dia(eti% 4atients with P':8 Search Strategy As a first ste4, the a&thors (FJ and =FA) sear%hed the ;<'>-A<3P&(;ed (Aational >i(rary of ;edi%ine, Fethesda, ;aryland, J"A) and #oo$le?"%holar data(ases &sin$ the followin$ !eywords in vario&s %om(inations" %yto!ine), $in$ival %revi%&lar fl&id), saliva), ser&m) and 4lasma), 'ata(ases were e54lored from 1..1 &4 to and in%l&din$ ;ay 2013, 6itles and a(stra%ts of arti%les that satisfied the sele%tion 4roto%ol were s%reened (y the a&thors and %he%!ed for a$reement, 6he f&ll?te5t of the arti%les C&d$ed (y title and a(stra%t to (e relevant were read and inde4endently assessed a$ainst the sele%tion 4roto%ol, 6his was followed (y hand?sear%hin$ of the referen%e lists of ori$inal and review st&dies that were fo&nd to (e relevant in the 4revio&s ste4 and on%e a$ain, any disa$reement (etween the a&thors was resolved via dis%&ssion (Fi$&re 1),

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

Figure #" A Diagrammatic $e%resentation of the Study Selection Protocol Study Selection Criteria 6he st&dy sele%tion %riteria en%om4assed the followin$: 1) 1ri$inal arti%lesE 2) h&man st&diesE 3) *eferen%e list of ori$inal and review st&diesE K) &se of statisti%al methodsE /) -ntervention: %yto!ine 4rofile in saliva, ser&m and # F in dia(eti% 4atients with P'E and 0) Arti%les 4&(lished only in <n$lish? lan$&a$e, 6he st&dies that were in%l&ded in the 4resent review were %ontrolled for %onfo&ndin$ 4arameters in%l&din$ a$e, smo!in$, (ody mass inde5, medi%ation and al%ohol %ons&m4tion, >etters to the editor, histori% reviews and &n4&(lished arti%les were e5%l&ded,

_______________ Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

Cytokine Profiles in Diabetic Patients with Periodontal Disease" &essons &earned from Previous Studies Unstimulated Whole Saliva osta et al,, (2010) investi$ated the %on%entrations of ->?0 in &nstim&lated whole saliva (J9") sam4les %olle%ted from ty4e 2 dia(eti% 4atients with P' (a$e ran$e 3/?0/ years), -n this st&dy ( osta et al,, 2010), the dia(eti% 4arti%i4ants (nLKK) had 62'; sin%e at least / years and had a 4oor meta(oli% %ontrol over the meta(oli% disorder (=emo$lo(in A1 (=(A1%) M 0N), 6he ->?0 %on%entrations in the saliva of P' 4atients with or witho&t 62'; were si$nifi%antly hi$her %om4ared to those in healthy %ontrols, 6hese res&lts are in a%%ordan%e with the f&n%tion of ->?0 on the mod&lation of 4eriodontal inflammation (Fartold and =aynes 1..1), ->?0 di%tates the transition from a%&te to %hroni% inflammation (y %han$in$ the nat&re of le&!o%yte infiltrate (from P;A ne&tro4hils to mono%ytes3ma%ro4ha$es) e5erts stim&latory effe%ts on 6 and F %ells, and ind&%es anti(ody formation, favorin$ a %hroni% inflammatory res4onse (Fartold and =aynes 1..1), #omes et al,, (2000) investi$ated the levels of interferon?$amma (-FA?O) and 6AF?B with P' in 4atients with 62';, -n this st&dy, nearly 03N of the 4arti%i4ants had well?%ontrolled 62'; (#omes et al,, 2000), 6he res&lts showed in%reased levels of -FA?O in 00N and a44ro5imately 1/N of the 4atients with severe? and moderate P' res4e%tivelyE however, there were no si$nifi%ant differen%es (etween 6AF?B levels (etween the $ro&4s (#omes et al,, 2000), -mm&nore$&latory 4ro4erties of -FA?O may a%t as a 4ossi(le e54lanation for the insi$nifi%ant differen%es in 6AF?B levels (etween dia(eti% s&(Ce%ts with moderate and severe P' (#emmell and "eymo&r 1..K), -t sho&ld however (e remem(ered that J9" is a mi5t&re of mole%&les derived from the maCor and minor salivary $lands, the m&%osal e4itheli&m, as well as the # F, 6herefore, it may (e ar$&ed that the e54ression of 4roinflammatory %yto!ines in J9" may in fa%t (e d&e to the lea!a$e of # F into the oral %avity of dia(eti% 4atients
_______________

with P', -n addition, salivary %yto!ine levels in J9" affe%ted mainly (y the amo&nt of (lood %ontamination (whi%h is a %ommon manifestation in 4atients with P') ("&h et al,, 200.), F&rther st&dies are ne%essary to f&lly e54lore the 4otential im4a%ts of dia(etes and P' on the e54ression of 4roinflammatory %yto!ines in J9", Gingival Crevicular Fluid # F is a ser&m trans&date whi%h e5ists in the $in$ival s&l%&s (as an inflammatory e5&date) of 4atients with P', "in%e # F %olle%tion is a non?invasive te%hni7&e, there is $rowin$ interest for its &se in monitorin$ 4eriodontal inflammation, -n their st&dy, FitDsimmons et al,, (2010) investi$ated the inde4endent and %om(ined asso%iations (etween # F ->?1@ and P', -n this st&dy, # F sam4les were %olle%ted from .3. individ&als and ->?1@ levels were investi$ated &sin$ <nDyme lin!ed imm&nosor(ent assay (<>-"A) (FitDsimmons et al,, 2010), 6he res&lts showed raised levels of ->?1@ in dia(eti% 4atients with P' %om4ared to non?dia(eti% %ontrols (<s4osito et al,, 2002), >i!ewise, another st&dy %om4ared the levels of (iomar!ers in the # F (etween 4atients with ty4e 1 dia(etes and healthy s&(Ce%ts d&rin$ e54erimental $in$ivitis ("alvi et al,, 2010), -n this st&dy, # F (iomar!ers were %om4ared (etween nine, ty4e 1 dia(etesi% and a similar n&m(er of %ontrol individ&als ("alvi et al, 2010), 6here was no si$nifi%ant differen%e in a$e and $ender (etween the $ro&4s, 6he res&lts showed that the mean # F (iomar!er levels for ->?1@ and matri5 metallo4roteinase (;;P)?I were si$nifi%antly hi$her in 4atients with ty4e 1 dia(etes %om4ared to healthy non?dia(eti% individ&als ("alvi et al,, 2010), "in%e ->?1@ is a 4roinflammatory and (one?resor(in$ %yto!ine that has (een 4ositively asso%iated with the 4ro$ression of P'E it may (e 4ost&lated that early treatment of 4eriodontal inflammatory %onditions may hel4 red&%e the levels of this %yto!ine in the # F, 6his may in t&rn, retard the 4eriodontal inflammatory %onditions in s&s%e4ti(le individ&als, s&%h as those with dia(etes, orrea et al,, (200I) investi$ated the effe%tiveness of non?s&r$i%al 4eriodontal thera4y in im4rovin$ the 4eriodontal stat&s

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

and red&%in$ the levels of ->?1@, ->?1I, ;;P?I and ?. levels in the # F amon$ 4eriodontitis 4atients with and witho&t 62';, 6he res&lts showed that non? s&r$i%al 4eriodontal thera4y si$nifi%antly red&%ed the %lini%al 4arameters of 4eriodontal inflammation (in%l&din$ $in$ival (leedin$ and 4ro(in$ 4o%!et de4th), 6his was a%%om4anied (y a si$nifi%ant red&%tion in ->?1@, ;;P?I and ? . levels in dee4 sites ( orrea et al,, 200I), =owever, in the st&dy (y GardePler et al,, (200I) 62'; did not infl&en%e the e54ression of 4roinflammatory mediators in the # F, "imilarly, res&lts (y <n$e(retson et al,, (2000) also showed that # F levels of ->?I are not asso%iated with the severity of 62';, F&rther st&dies are warranted in this re$ard, Serum -n%reased %ir%&latin$ levels of ->?0 have (een asso%iated with the 4ro$ression of dia(etes (<s4osito et al,, 2002), Aon? s&r$i%al 4eriodontal thera4y has (een re4orted to si$nifi%antly red&%e the ser&m %on%entrations of ->?0 there(y red&%in$ the elevated $ly%emi% levels as well as 4eriodontal inflammation, 6he st&dy (y 1H onnell et al,, (200I) investi$ated the effe%t of non?s&r$i%al 4eriodontal treatment on the levels of %ir%&latin$ 4roinflammatory %yto!ines in dia(eti% individ&als with P', 6he res&lts showed a si$nifi%ant red&%tion in the ser&m %on%entrations of ->?0 and ->? 12 followin$ 4eriodontal thera4y in 4atients with 62'; (1H onnell et al,, 200I), 6AF?B has (een re4orted to 4lay a si$nifi%ant role in the 4atho$enesis of 62'; (y inhi(itin$ ins&lin a%tion (Ar$iles et al,, 1..KE "alvi et al,, 1..2a), *es&lts (y 'aQ et al,, (11) showed a si$nifi%ant red&%tion in the ser&m %on%entrations of 6AF?B in ty4e 2 dia(eti% 4atients with P' followin$ non?s&r$i%al 4eriodontal treatment, A dose?res4onse relationshi4 (etween P' severity and ser&m levels of 6AF? B has also (een re4orted ("alvi et al,, 1..2a), *es&lts (y "alvi et al,, (1..2a) s&$$ested that the dia(eti% state res&lts in an &4re$&lated mono%yti% 6AF?B se%retion whi%h, in the 4resen%e of $ram?ne$ative (a%teria, intensifies the e54ression of P',
_______________

!"ression o# $ther Cyto%ines in the Saliva& Serum and Gingival Crevicular Fluid o# 'iabetic Patients (ith Periodontal 'isease +isfatin (initially termed, h&man 4re?F?%ell %olony enhan%in$ fa%tor) is a /2 !ilodalton mole%&le, se%reted (y adi4o%ytes, -t has (een s&$$ested that visfatin ind&%es the 4rod&%tion of ->?1@, 6AF?B and ->?0 d&rin$ infe%tion and inflammation, 6o o&r !nowled$e from inde5ed literat&re, only one st&dy has assessed visfatin levels in the # F and ser&m of ty4e 2 dia(eti% 4atients with 4eriodontal disease (Pradee4 et al,, 2012), -n this st&dy, 30 4atients were divided into three $ro&4s: $ro&4 1 (10 healthy), $ro&4 2 (10 4atients with well?%ontrolled 62'; and P'), and $ro&4 3 (10 individ&als with P and witho&t dia(etes), +isfatin levels in the ser&m and # F were determined &sin$ <>-"A, 6he res&lts demonstrated that the mean visfatin %on%entration was hi$her in ser&m and # F in individ&als with 62'; with P' %om4ared to healthy %ontrols (Pradee4 et al,, 2012), F&rthermore, the res&lts also showed that ser&m and # F visfatin levels %orrelated 4ositively with the %lini%al 4eriodontal inflammatory 4arameters (Pradee4 et al,, 2012), -t is tem4tin$ to s4e%&late that visfatin are also hi$her in dia(eti% 4atients with P' as %om4ared to systemi%ally healthy %ontrolE however, f&rther st&dies are warranted to assess this relationshi4, *esistin, an adi4o%yto!ine that ind&%es ins&lin resistan%e, is maCorly e54ressed in adi4o%ytes and 4eri4heral (lood monon&%lear %ells, <54ression of resistin is in%reased in inflammatory diseases as well as dia(etes mellit&s, and is &4re$&lated (y (a%terial 4atho$ens and 4roinflammatory %yto!ines (=iroshima et al,, 2012), -n inde5ed literat&re, only one st&dy %o&ld (e %ited whi%h aimed to identify resistin in h&man # F amon$ 4atients with and witho&t 4eriodontitis and dia(etes (=iroshima et al,, 2012), -n this st&dy, # F sam4les were %olle%ted from 2K 4atients with P', 1I 4atients with dia(etes mellit&s? related P' and 21 healthy %ontrols, *esistin in $in$ival %revi%&lar fl&id was determined &sin$ western (lot analysis and <>-"A, 6he res&lts demonstrated that the resistin level

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

in the # F from 4atients with P' or dia(etes mellit&s?related P' were si$nifi%antly hi$her than those identified in healthy %ontrols (=iroshima et al,, 2012), -t is hy4othesiDed that resistin levels in the saliva and3or ser&m of 4atients with 1' and dia(etesE however, this hy4othesis is yet to (e %onfirmed via f&t&re investi$ations,

Discussion -n the 4resent %om4rehensive literat&re review, we aimed to s&mmariDe the 4roinflammatory %yto!ines that are e54ressed in the saliva, ser&m and # F of dia(eti% 4atients with P', From the literat&re reviewed, we o(served that there is a dysre$&lation in %yto!ine 4rod&%tion in dia(eti% 4atients with P' as %om4ared to healthy %ontrols (Fi$&re 2),

Figure '" A Diagrammatic $e%resentation of the Cytokine Profile in the Saliva, Gingival Crevicular Fluid and Serum of Diabetic Patients with Periodontal Disease
->: -nterle&!in -FA?O: -nterferon?$amma ;;P: ;atri5 metallo4roteinase 6AF?B: 6&mor ne%rosis fa%tor?al4ha

Predominantly, %onne%tive tiss&e destr&%tion that ta!es 4la%e in 4atients with 4oorly?%ontrolled dia(etes and P' res&lts from the intera%tion (etween (a%teria (and
_______________

their 4rod&%ts) and P;A %ells (Ginane and Fartold 2002E ;ealey and 1%am4o 2002), -n addition, it has (een 4ro4osed that 4atients with 4oorly?%ontrolled dia(etes have more

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

severe P' d&e to the in%reased 4rod&%tion and a%%&m&lation of $l&%ose mediated A#<s in the 4eriodontal tiss&es as %om4ared to 4atients with well?%ontrolled dia(etes and healthy %ontrols (#rossi and #en%o 1..IE Javed et al,, 2002), hroni% hy4er$ly%emia affe%ts the mi$ration and 4ha$o%yti% a%tivity of monon&%lear and P;A 4ha$o%yti% %ells res&ltin$ in esta(lishment of more 4atho$eni% s&(?$in$ival flora, 6his tri$$ers an infe%tion?mediated 4athway and dysre$&lates %yto!ine 4rod&%tion and e54ression, F&rthermore, P' am4lifies the ma$nit&de of the ma%ro4ha$e res4onse to A#<s there(y enhan%in$ %yto!ine 4rod&%tion and o5idative stress th&s am4lifyin$ the %lassi%al 4athway of dia(eti% %onne%tive tiss&e de$radation, destr&%tion and 4roliferation, #rossi and #en%o (1..I) 4ro4osed that P' mediated %yto!ine synthesis and se%retion may am4lify the ma$nit&de of the A#< mediated %yto!ine res4onse and vi%e versa, Proinflammatory %yto!ines s&%h as ->?0 and 6AF?B, 4romote 4eriodontal inflammation, in 4art, (y stim&latin$ the e54ression of %hemo!ines s&%h as mono%yte %hemota%ti% 4rotein 1 and ma%ro4ha$e inflammatory 4rotein 1 that dire%t the mi$ration of le&!o%ytes into the vessel walls (#im(rone et al,, 1../), -t is well?!nown that a dire%t relationshi4 e5ists (etween o(esity and 62'; (;ealey and 1%am4o 2002), Adi4ose tiss&es, 4arti%&larly vis%eral fat, have (een asso%iated with ins&lin resistan%e sin%e they may %a&se ins&lin resistan%e thro&$h the release of free fatty a%ids (FFAs), Adi4o%ytes and ma%ro4ha$es asso%iated with vis%eral fat also synthesiDe ->?0 and 6AF? B (maCor %yto!ines res4onsi(le for ind&%in$ ins&lin resistan%e at the re%e4tor level), From the literat&re reviewed, we learned that ->?0 has (een identified in the saliva, ser&m as well as # F of dia(eti% 4atients with P', -t is therefore tem4tin$ to s4e%&late that $ly%emi% %ontrol red&%es 4eriodontal inflammation as well as ->?0 and 6AF? B levels in saliva, ser&m and # F of 4atients with dia(etes, =owever, f&rther st&dies are warranted to verify this hy4othesis, ->?1I is a 4leiotro4i% 4roinflammatory %yto!ine that 4lays essential re$&latory f&n%tions in the innate
_______________

imm&ne res4onse, A%tivation of interle&!in? 1I has (een fo&nd to (e involved in the 4atho$enesis of meta(oli% syndrome, ->?1@, a %lassi% 4yro$en, %a&ses redness in 4eriodontal disease, d&e in 4art to the %a4illary wall 4ermea(ility that o%%&rs in res4onse to this %yto!ine, F&rthermore, ->? 1@ stim&lates %olla$enase 4rod&%tion, whi%h in t&rn (rea!s down 4eriodontal %onne%tive tiss&es and leads to the formation of osteo%lasts and %on%omitant alveolar (one loss, Altho&$h ->?1 @ has (een identified in the # F and ser&m of dia(eti% 4atients with P', f&rther st&dies are needed to determine the salivary levels of ->?1 @ in dia(eti% 4atients with 4eriodontal disease, '&e to a limited n&m(er of st&dies that have assessed the e54ression of visfatin and resistin in # F of dia(eti% 4atients with P', a&thors of the 4resent %om4rehensive review find it e5i$ent to %omment on the si$nifi%an%e of these %yto!ines with referen%e to dia(etes and P', 1n a %omm&nity level, determination of %yto!ines (4arti%&larly ->?0) in saliva, ser&m or # F may (e a &sef&l tool in estimatin$ the 4revalen%e of P', F&rthermore, s&%h imm&nolo$i% assays hel4 also in 4redi%tin$ hy4er$ly%emia (or latent dia(etes) in &ndia$nosed individ&als, Conclusion *aised levels of 4roinflammatory %yto!ines (in%l&din$ ->?1@, ->?0 and 6AF) in the saliva, ser&m and # F of dia(eti% 4atients with P' may (e a val&a(le tool in the early dete%tion of P', <levated %on%entrations of 4roinflammatory %yto!ines in the saliva, ser&m and3or # F may also (e indi%ative of latent8 dia(etes in &ndia$nosed individ&als, $eferences Ar$iles, J, ;,, >o4eD?"oriano, J, R >o4eD? "oriano, F, J, (1..K), 8 yto!ines and 'ia(etes: 6he Final "te4: -nvolvement of 6AF?al4ha in Foth 6y4e - and -- 'ia(etes ;ellit&s,8 0ormone and 1etabolic Research , 20(10), KK2?.,

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

Fandyo4adhyay, ',, ;arlow, A, ;,, Fernandes, J, G, R >eite, *, ", (2010), 8Periodontal 'isease Pro$ression and #ly%aemi% ontrol amon$ #&llah Afri%an Ameri%ans with 6y4e?2 'ia(etes,8 Journal of 2linical Periodontology, 32(0), /01?., Fartold, P, ;, R =aynes, ', *, (1..1), 8-nterle&!in?0 Prod&%tion (y =&man #in$ival Fi(ro(lasts,8 Journal of Periodontal Research, 20(K), 33.?K/, hen, >,, 9ei, F,, >i, J,, >i&, F,, S&an, ',, Sie, F, R Than$, J, (2010), 8Asso%iation of Periodontal Parameters with ;eta(oli% >evel and "ystemi% -nflammatory ;ar!ers in Patients with 6y4e 2 'ia(etes,8 Journal of Periodontology, I1(3), 30K?21, ole, , ;,, "&ndararaC, G, P,, >eite, *, ",, Aarei!a, A,, "late, <, =,, "anders, J, J,, >o4es? +irella, ;, F, R =&an$, U, (200I), 8A 6rend of -n%rease in Periodontal -nterle&!in?0 <54ression a%ross Patients with Aeither 'ia(etes nor Periodontal 'isease, Patients with Periodontal 'isease Alone, and Patients with Foth 'iseases,8 Journal of Periodontal Research, K3(0), 212?22, orrea, F, 1, F,, #on%alves, ',, Fi$&eredo, , ;, ",, #&stafsson, A, R 1rri%o, ", *, P, (200I), 86he "hort?6erm <ffe%tiveness of Aon? "&r$i%al 6reatment in *ed&%in$ >evels of -nterle&!in?1(eta and Proteases in #in$ival revi%&lar Fl&id from Patients with 6y4e 2 'ia(etes ;ellit&s and hroni% Periodontitis,8 Journal of Periodontology, 2.(11), 21K3?/0, osta, P, P,, 6revisan, #, >,, ;a%edo, #, 1,, Palioto, ', F,, "o&Da, ", >, ",, #risi, ;, F, ;,, Aovaes, A, F,, Jr, R 6a(a, ;,, Jr, (2010), 8"alivary -nterle&!in?0, ;atri5 ;etallo4roteinase?I, and 1steo4rote$erin in Patients with Periodontitis and 'ia(etes,8 Journal of Periodontology, I1(3), 3IK?.1, &tando, A,, #omeD?;oreno, #,, +illal(a, J,, Ferrera, ;, J,, <s%ames, #, R A%&na? astrovieCo, ', (2003), 8*elationshi4 (etween "alivary ;elatonin >evels and Periodontal "tat&s in 'ia(eti% Patients,8 Journal of Pineal Research, 3/(K), 23.?KK, 'a$, A,, Firat, <, 6,, Ari!an, ",, Gadiro$l&, A, G, R Ga4lan, A, (200.), 86he <ffe%t of
_______________

Periodontal 6hera4y on "er&m 6AF?al4ha and =(A1% >evels in 6y4e 2 'ia(eti% Patients,8 )ustralian Dental Journal, /K(1), 12?22, <n$e(retson, ",, herto$, *,, Ai%hols, A,, =ey?=adavi, J,, elenti, *, R #r(i%, J, (2002), 8Plasma >evels of 6&mo&r Ae%rosis Fa%tor? Al4ha in Patients with hroni% Periodontitis and 6y4e 2 'ia(etes,8 Journal of 2linical Periodontology, 3K(1), 1I?2K, <n$e(retson, ", P,, +oss&$hi, F,, =ey?=adavi, J,, <min$il, #, R #r(i%, J, 6, (2000), 86he -nfl&en%e of 'ia(etes on #in$ival revi%&lar Fl&id Feta?#l&%&ronidase and -nterle&!in?I,8 Journal of 2linical Periodontology, 33(11), 2IK?.0, <s4osito, G,, Aa44o, F,, ;arfella, *,, #i&$liano, #,, #i&$liano, F,, iotola, ;,, V&a$liaro, >,, eriello, A, R #i&$liano, ', (2002), 8-nflammatory yto!ine on%entrations are A%&tely -n%reased (y =y4er$ly%emia in =&mans: *ole of 15idative "tress,8 2irculation, 100(10), 2002?22, FitDsimmons, 6, *,, "anders, A, <,, Fartold, P, ;, R "lade, #, ', (2010), 8>o%al and "ystemi% Fiomar!ers in #in$ival revi%&lar Fl&id -n%rease 1dds of Periodontitis,8 Journal of 2linical Periodontology, 32(1), 30?0, #emmell, <, R "eymo&r, #, J, (1..K), 8;od&lation of -mm&ne *es4onses to Periodontal Fa%teria,8 2urrent .pinion in Periodontology, 2I?3I, #im(rone, ;, A,, Jr,, y(&ls!y, ;, -,, G&me, A,, ollins, 6, R *esni%!, A, (1../), 8+as%&lar <ndotheli&m, An -nte$rator of Patho4hysiolo$i%al "tim&li in Athero$enesis,8 )nnals of the New 3or4 )cademy of 5ciences, 2KI, 122?31E dis%&ssion 131?2, #omes, ;, A, F,, *odri$&es, F, =,, Afonso? ardoso, ", *,, F&so, A, ;,, "ilva, A, #,, Favoreto, ",, Jr, R "o&Da, ;, A, (2000), 8>evels of -mm&no$lo(&lin A1 and ;essen$er *AA for -nterferon #amma and 6&mor Ae%rosis Fa%tor Al4ha in 6otal "aliva from Patients with 'ia(etes ;ellit&s 6y4e 2 with hroni% Periodontal 'isease,8 Journal of Periodontal Research, K1(3), 122?I3,

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry

#rossi, ", #, R #en%o, *, J, (1..I), 8Periodontal 'isease and 'ia(etes ;ellit&s: A 6wo?9ay *elationshi4,8 )nnals of Periodontology, 3(1), /1?01, =iroshima, U,, Fando, ;,, -na$a!i, U,, ;ihara, ,, Gatao!a, ;,, ;&rata, =,, "hinohara, U,, Aa$ata, 6, R Gido, J, (2012), 8*esistin in #in$ival revi%&lar Fl&id and -nd&%tion of *esistin *elease (y Por4hyromonas #in$ivalis >i4o4olysa%%haride in =&man Ae&tro4hils,8 Journal of Periodontal Research, K2(/), //K?02, =olloway, A, F,, *ao, ", R "hannon, ;, F, (2002), 8*e$&lation of yto!ine #ene 6rans%ri4tion in the -mm&ne "ystem,8 1olecular *mmunology, 3I(I), /02?I0, -oannido&, <,, Gao, ',, han$, A,, F&rleson, J, R 'on$ari?Fa$tDo$lo&, A, (2000), 8<levated "er&m -nterle&!in?0 (->?0) in "olid?1r$an 6rans4lant *e%i4ients is Positively Asso%iated with 6iss&e 'estr&%tion and ->? 0 #ene <54ression in the Periodonti&m,8 Journal of Periodontology, 22(11), 1I21?I, Javed, F,, Al?As!ar, ;,, "amaranaya!e, >, P, R Al?=eDaimi, G, (2013a), 8Periodontal 'isease in =a(it&al i$arette "mo!ers and Aonsmo!ers with and 9itho&t Predia(etes,8 )merican Journal of the 1edical 5ciences, 3K/(2), .K?I, Javed, F,, Glin$s4or, >,, "&ndin, J,, Altamash, ;,, Glin$e, F, R <n$strom, P, <, (200.), 8Periodontal onditions, 1ral andida Al(i%ans and "alivary Proteins in 6y4e 2 'ia(eti% "&(Ce%ts with <m4hasis on #ender,8 612 .ral 0ealth, ., 12, Javed, F,, Aasstrom, G,, Fen%himol, ',, Altamash, ;,, Glin$e, F, R <n$strom, P, <, (2002), 8 om4arison of Periodontal and "o%ioe%onomi% "tat&s (etween "&(Ce%ts with 6y4e 2 'ia(etes ;ellit&s and Aon? 'ia(eti% ontrols,8 Jo&rnal of Periodontolo$y, 2I(11), 2112?., Javed, F, R *omanos, #, <, (200.), 8-m4a%t of 'ia(etes ;ellit&s and #ly%emi% ontrol on the 1sseointe$ration of 'ental -m4lants: A "ystemati% >iterat&re *eview,8 Journal of Periodontology, I0(11), 121.?30,
_______________

Javed, F,, 6hafeed Al$hamdi, A, ",, ;i!ami, 6,, ;ehmood, A,, Ahmed, =, F,, "amaranaya!e, >, P, R 6enen(a&m, =, , (2013(), 8<ffe%t of #ly%emi% ontrol on "elf?Per%eived 1ral =ealth, Periodontal Parameters and Alveolar Fone >oss amon$ Patients with Predia(etes,8 Journal of Periodontology, Gardesler, >,, F&d&neli, A,, Fiyi!o$l&, F,, etin!al4, ", R G&t&!%&ler, A, (200I), 8#in$ival revi%&lar Fl&id P#<2, ->?1(eta, t? PA, PA-?2 >evels in 6y4e 2 'ia(etes and *elationshi4 with Periodontal 'isease,8 2linical 6iochemistry, K1(10?11), I03?I, Gardesler, >,, F&d&neli, A,, etin!al4, ", R Ginane, ', F, (2010), 8Adi4o!ines and -nflammatory ;ediators after -nitial Periodontal 6reatment in Patients with 6y4e 2 'ia(etes and hroni% Periodontitis,8 Journal of Periodontology, I1(1), 2K?33, Ginane, ', F, R Fartold, P, ;, (2002), 8 lini%al *elevan%e of the =ost *es4onses of Periodontitis,8 Periodontology "###, K3, 22I? .3, >alla, <,, Ga4lan, ",, han$, ",? ;, J,, *oth, #, A,, elenti, *,, =in%!ley, G,, #reen(er$, <, R Pa4a4ano&, P, A, (2000), 8Periodontal -nfe%tion Profiles in 6y4e 1 'ia(etes,8 Journal of 2linical Periodontology, 33(12), I//?02, >alla, <,, Ga4lan, ",, Uan$, J,, *oth, #, A,, Pa4a4ano&, P, A, R #reen(er$, ", (2002), 8<ffe%ts of Periodontal 6hera4y on "er&m ? rea%tive Protein, s<?"ele%tin, and 6&mor Ae%rosis Fa%tor?Al4ha "e%retion (y Peri4heral Flood?'erived ;a%ro4ha$es in 'ia(etes, A Pilot "t&dy,8 Journal of Periodontal Research, K2(3), 22K?I2, ;ealey, F, >, R 1%am4o, #, >, (2002), 8'ia(etes ;ellit&s and Periodontal 'isease,8 Periodontology "###, KK, 122?/3, Aarei!a, A,, ;aldonado, A,, =e, >,, #ame, F, A,, "late, <, =,, "anders, J, J,, >ondon, ", ',, >o4es?+irella, ;, F, R =&an$, U, (2002), 8=i$h #l&%ose?Foosted -nflammatory *es4onses to >i4o4olysa%%haride are "&44ressed (y "tatin,8 Journal of Periodontal Research, K2(1), 31?I,

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0

Jo&rnal of *esear%h and Pra%ti%e in 'entistry 10

Aavarro?"an%heD, A, F,, Faria?Almeida, *, R Fas%ones?;artineD, A, (2002), 8<ffe%t of Aon?"&r$i%al Periodontal 6hera4y on lini%al and -mm&nolo$i%al *es4onse and #ly%aemi% ontrol in 6y4e 2 'ia(eti% Patients with ;oderate Periodontitis,8 Journal of 2linical Periodontology, 3K(10), I3/?K3, Aishim&ra, F, R ;&rayama, U, (2001), 8Periodontal -nflammation and -ns&lin *esistan%e??>essons from 1(esity,8 Journal of Dental Research, I0(I), 10.0?K, Aishim&ra, F,, 6ani$&%hi, A,, Uama$&%hi? ;orimoto, ;,, "o$a, U,, -wamoto, U,, Go!e$&%hi, ",, G&roe, A,, F&!&shima, ;,, Aa!ai, U, R "eino, U, (2000), 8Periodontal -nfe%tion and 'ysli4idemia in 6y4e 2 'ia(eti%s: Asso%iation with -n%reased =;#? oA *ed&%tase <54ression,8 0ormone and 1etabolic Research, 3I(I), /30?/, 1H onnell, P, A, A,, 6a(a, ;,, AomiDo, A,, Foss Freitas, ;, ,, "&aid, F, A,, Jyem&ra, ", A,, 6revisan, #, >,, Aovaes, A, F,, "o&Da, ", >,, Palioto, ', F, R #risi, ;, F, (200I), 8<ffe%ts of Periodontal 6hera4y on #ly%emi% ontrol and -nflammatory ;ar!ers,8 Journal of Periodontology, 2.(/), 22K?I3, Pradee4, A, *,, *a$havendra, A, ;,, "harma, A,, Patel, ", P,, *aC&, A,, Gathariya, *,, *ao, A, ", R Aai!, ", F, (2012), 8Asso%iation of "er&m and revi%&lar +isfatin >evels in Periodontal =ealth and 'isease with 6y4e 2 'ia(etes ;ellit&s,8 Journal of Periodontology, I3(/), 02.?3K, Pradee4, A, *,, 6horat ;anoC!&mar, ",, #arima, #, R *aC&, A, (2010), 8"er&m >evels of 1n%ostatin ; (a $4 130 yto!ine): An -nflammatory Fiomar!er in Periodontal 'isease,8 6iomar4ers, 1/(3), 222?I2, "alvi, #, <,, Fe%!, J, ', R 1ffen(a%her, ", (1..I), 8P#<2, ->?1 Feta, and 6AF?Al4ha *es4onses in 'ia(eti%s as ;odifiers of Periodontal 'isease <54ression,8 )nnals of Periodontology, 3(1), K0?/0, "alvi, #, <,, ollins, J, #,, Ualda, F,, Arnold, *, *,, >an$, A, P, R 1ffen(a%her, ", (1..2a), 8;ono%yti% 6AF Al4ha "e%retion Patterns in -''; Patients with Periodontal 'iseases,8 Journal of 2linical Periodontology, 2K(1), I?
_______________

10, "alvi, #, <,, Fran%o, >, ;,, Fra&n, 6, ;,, >ee, A,, *&t$er Persson, #,, >an$, A, P, R #ianno(ile, 9, +, (2010), 8Pro?inflammatory Fiomar!ers d&rin$ <54erimental #in$ivitis in Patients with 6y4e 1 'ia(etes ;ellit&s: A Proof?of? on%e4t "t&dy,8 Journal of 2linical Periodontology, 32(1), .?10, "alvi, #, <,, Ualda, F,, ollins, J, #,, Jones, F, =,, "mith, F, 9,, Arnold, *, *, R 1ffen(a%her, ", (1..2(), 8-nflammatory ;ediator *es4onse as a Potential *is! ;ar!er for Periodontal 'iseases in -ns&lin?'e4endent 'ia(etes ;ellit&s Patients,8 Journal of Periodontology, 0I(2), 122?3/, "&h, G,? -,, Gim, U,? G, R Gho, =,? ", (200.), 8"alivary >evels of ->?1(eta, ->?0, ->?I, and 6AF?Al4ha in Patients with F&rnin$ ;o&th "yndrome,8 )rchi7es of .ral 6iology, /K(.), 2.2?I02,

Fawad Javed and Asma Ahmed (2013), Journal of Research and Practice in Dentistry( '1-: 10,/12132013,./0..0