2014/2015
Paula C is ina Ca doso Teixei a
Pso iasis pa ien s wi h obesi y and
ype 2 diabe es: he e ec o
glucagon-like pep ide-1 (GLP-1)
ecep o agonis s
ma ço, 2015
Mes ado In eg ado em Medicina
Á ea: De ma ologia
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Dou o a So ia Magina
T abalho o ganizado de aco do com as no mas da e is a:
Jou nal o he Eu opean Academy o De ma ology and
Vene eology
Paula C is ina Ca doso Teixei a
Pso iasis pa ien s wi h obesi y and
ype 2 diabe es: he e ec o
glucagon-like pep ide-1 (GLP-1)
ecep o agonis s
ma ço, 2015
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De ma ologia
TÍTULO DISSERTAÇÃO/MONOGRAFIA ( isca o que não in e essa)
Pso iasis pa ien s wi h obesi y and ype 2 diabe es: he e ec o glucagon-like pep ide-1 (GLP-1)
ecep o agonis s
ORIENTADOR
P o . D a. So ia Magina
COORIENTADOR (se aplicá el)
É au o izada a ep odução in eg al des a Disse ação/Monog a ia ( isca o que não in e essa) pa a
e ei os de in es igação e de di ulgação pedagógica, em p og amas e p ojec os coo denados pela
FMUP.
Faculdade de Medicina da Uni e sidade do Po o, _03 /_03_/_2015_
Assina u a con o me ca ão de iden i icação:
DEDICATÓRIA
“I you ocus on he p oblem, you can' see he solu ion. Ne e ocus on he p oblem! See
wha no one else sees. See wha e e yone chooses no o see... ou o ea , con o mi y o
laziness. See he whole wo ld as new each day “
Pa ch Adams

MONOGRAFIA
Pso iasis pa ien s wi h obesi y and ype 2 diabe es: he
e ec o glucagon-like pep ide-1 (glp-1) ecep o
agonis s
Redigida de aco do com as no mas da e is a Jou nal o he Eu opean
Academy o De ma ology and Vene eology
Re iew A icle
1
PSORIASIS PATIENTS WITH OBESITY AND TYPE 2 DIABETES: THE EFFECT
OF GLUCAGON-LIKE PEPTIDE-1 (GLP-1) RECEPTOR AGONISTS
2800 wo ds
2 ables
2 igu es
Au ho in o ma ion
P. Teixei a1,3, S. Magina1,2,3
1Faculdade de Medicina da Uni e sidade do Po o, Po o, Po ugal; 2Depa men o
De ma ology; 3Depa men o Pha macology and The apeu ics, Hospi al de São João, Po o,
Po ugal
Co espondence
P. Teixei a
Faculdade de Medicina da Uni e sidade do Po o, Alameda P o . He nâni Mon ei o, 4200 -
319 Po o, Po ugal
Tel 220426700 Fax 225513643
Email: paula.ca doso. e[email p o ec ed]
Funding Sou ces
None
Con lic o in e es
All au ho s decla e no con lic s o in e es
2
ABSTRACT
Pa ien s wi h pso iasis ha e a high p e alence o diabe es melli us (DM), obesi y and
ca dio ascula diseases. Glucagon-like pep ide-1 ecep o (GLP-1R) agonis s is a ecen
he apy used in obese pa ien s wi h ype 2 diabe es. This new d ugs imp o e glycaemic
con ol and educe weigh . Besides, GLP-1R is p esen on some cells o he immune sys em.
Recen s udies sugges ed ha GLP-1R agonis s may imp o e pso iasis.
We e iewed he li e a u e o examine he e icacy o GLP-1R agonis s on clinical se e i y o
pso iasis pa ien s wi h obesi y and ype 2 diabe es and o e alua e he mechanism by which
GLP-1R agonis s exe hei e ec s. Pso iasis pa ien s, wi h ype 2 diabe es and obesi y, seem
o ha e a signi ican imp o emen in pso iasis se e i y and quali y o li e, a e GLP-1R
agonis he apy. They also showed a dec eased in weigh and choles e ol le els and an
imp o emen in glycaemic con ol. The e ec s on pso ia ic lesions occu a e a ew weeks
o ea men , e en be o e he me abolic imp o emen occu s. GLP-1R agonis s appea o ha e
an added bene icial e ec on pso iasis pa ien s, possibly due o i s immunomodula o y e ec s.
Fu he mo e, his ea men can also imp o e o he como bidi ies ha may be associa ed, such
as diabe es and obesi y. In conclusion, GLP-1R agonis s may be a use ul adjunc i e he apy
o he ea men o pso iasis in diabe ics and obese pa ien s.
3
INTRODUCTION
Pso iasis is a ch onic in lamma o y disease ha a ec s 2-3% o wo ld’s popula ion.
His opa hologically is cha ac e ized by hipe p oli e a ion o epide mal ke a inocy es and
hype ke a osis, de mal in lamma o y in il a e and angiogenesis. The in lamma o y in il a e
consis s mainly o dend i ic cells, mac ophages, and T cells in he de mis and neu ophils,
wi h some T cells in he epide mis (1, 2). Pso iasis is conside ed an immune-media ed
in lamma o y skin diso de (3), in which Th17 pa hway plays an impo an ole (1), suppo ed
by he good esul s wi h IL-17 based he apies (4).
Pso iasis was conside ed a disease con ined o he skin (5), bu ecen indings ha e shown
ha pa ien s wi h pso iasis also ha e an inc eased isk o ca dio ascula disease and mo ali y,
as well as me abolic synd ome and i s componen s (6-8). Se e al s udies ha e shown ha
pa ien s wi h pso iasis ha e a high p e alence o DM, hype ension, obesi y, hype lipidaemia
and smoking (9-11). So, i is impo an o app oach pso iasis as a sys emic diso de .
Pso iasis pa ien s ha e a highe isk o de eloping impai ed glucose ole ance and ype 2
diabe es (12-14). Obesi y seems o be mo e common in pso iasis pa ien s when compa ed
wi h he gene al popula ion (15) and is conside ed a isk ac o o he de elopmen o
pso iasis (6). The eason behind his associa ion emains unknown, bu di e en s udies
sugges ha obesi y, as a ch onic in lamma o y s a e, may con ibu e o he de elopmen and
agg a a ion o pso ia ic lesions (16, 17).
Two new d ug classes based on he ac ions o he inc e in ho mones ha e been app o ed o
he apy o ype 2 diabe es - inc e in enhance s and inc e in mime ics (18). Inhibi o s o
dipep idyl pep idase 4 (DPP4 - he enzyme esponsible o he apid deg ada ion o GLP-1),
inc ease inc e ins le els and enhance GLP-1 ac ion. I is known ha DPP4 is also exp essed
on T cells su ace, ha ing an impo an ole in ac i a ing T cells (19). Howe e , only wo
cases epo s showed ha DPP4 inhibi o s ha e posi i e e ec s in he ea men o pso iasis
pa ien s wi h diabe es (19, 20). Glucagon-like pep ide-1 ecep o (GLP-1R) agonis s (inc e in
mime ics – li aglu ide and exena ide) ha e been used in obese pa ien s wi h ype 2 diabe es.
This he apy imp o es glycaemic con ol and educes weigh . Se e al s udies sugges ha
pso iasis pa ien s wi h obesi y and DM2, ea ed wi h GLP-1R agonis s, exhibi ed a
signi ican imp o emen o pso iasis lesions, possibly due o i s an i-in lamma o y e ec (21).
10
skin om pso iasis pa ien s (31). Came on e al demons a ed ha cells exp essing NK
ma ke s and NK-T cell ma ke s a e p esen in pso iasis lesions (32). Recen da a, epo ed by
T. Ahe n e al and Hogan e al, show ha ci cula ing iNKT cells inc eased and plaque iNKT
cells dec eased a e li aglu ide ea men in pso iasis pa ien s wi h ype 2 diabe es and
obesi y(22, 25). These esul s sugges ha GLP-1R agonis s may ha e a ole in pso iasis
ea men , since hey seem o ha e di ec and indi ec e ec s on immune cells in ol ed in
pso iasis pa hogenesis.
O he s udies ha e shown ha GLP-1 le els also inc eased a e gas ic bypass su ge y. Some
case epo s ha e desc ibed ha pso iasis imp o es immedia ely a e his p ocedu e in obese
pa ien s (33). Changes on pso iasis mani es a ions occu be o e any weigh loss and coincide
wi h a signi ican inc ease in GLP-1 le els (34-36). Fau schou e al sugges ed ha GLP-1 is
esponsible o his e ec . The changes on GLP-1 le els a e p esumed o be caused by he
su gically-in oduced e ou ing o inges ed nu ien s di ec ly o he dis al pa o jejunum,
whe e GLP-1 eleasing L cells a e abundan ( igu e 2). GLP-1 is sec e ed o he blood s eam
upon ood inges ion when luminal nu i ional componen s con ac wi h he apical pa o he L
cells. These da a suppo he hypo hesis ha GLP-1 is esponsible o he posi i e e ec
obse ed in pso iasis and obese pa ien s wi h ype 2 diabe es (37).
Mos o he s udies we e limi ed by small sample size, sho du a ion, lack o compa a i e
g oups and placebo e ec . Fu he s udies a e ob iously needed, including andomised
clinical ials. GLP-1R agonis s appea o ha e an added bene icial e ec on pso iasis
pa ien s, possibly due o i s immunomodula o y e ec s. Besides, his ea men can also
imp o e o he como bidi ies ha may be associa ed, such as diabe es and obesi y.
In conclusion, GLP-1R agonis s seem o ha e a posi i e e ec on pso iasis se e i y and
quali y o li e. I appea s o ac by an immune mechanism, h ough a educ ion o IL-17
exp ession and de mal γδ T-cells. These esul s sugges ha GLP-1R agonis s may be a use ul
adjunc i e he apy o he ea men o pso iasis in diabe ics and obese pa ien s.

11
ACKNOWLEDGMENTS
I would like o exp ess my g a i ude o my supe iso , P o . Doc o So ia Magina, o he help
h ough he cou se o his wo k.
REFERENCES
1. Nes le FO, Kaplan DH, Ba ke J. Pso iasis. The New England jou nal o medicine.
2009;361(5):496-509.
2. Schon MP, Boehncke WH. Pso iasis. The New England jou nal o medicine.
2005;352(18):1899-912.
3. Jadali Z, Eslami MB. T cell immune esponses in pso iasis. I anian jou nal o alle gy,
as hma, and immunology. 2014;13(4):220-30.
4. Lonnbe g AS, Zacha iae C, Sko L. Ta ge ing o in e leukin-17 in he ea men o
pso iasis. Clinical, cosme ic and in es iga ional de ma ology. 2014;7:251-9.
5. Somme DM, Jenisch S, Suchan M, Ch is ophe s E, Weichen hal M. Inc eased
p e alence o he me abolic synd ome in pa ien s wi h mode a e o se e e pso iasis.
A chi es o de ma ological esea ch. 2006;298(7):321-8.
6. Go lieb AB, Dann F. Como bidi ies in pa ien s wi h pso iasis. The Ame ican jou nal
o medicine. 2009;122(12):1150.e1-9.
7. G ozde I, Ko man N, Tsanko N. Pso iasis as a sys emic disease. Clinics in
de ma ology. 2014;32(3):343-50.
8. Gisondi P, Tessa i G, Con i A, Piase ico S, Schianchi S, Pese ico A, e al. P e alence
o me abolic synd ome in pa ien s wi h pso iasis: a hospi al-based case-con ol s udy.
The B i ish jou nal o de ma ology. 2007;157(1):68-73.
9. Ahleho O, Gislason GH, Cha lo M, Jo gensen CH, Lindha dsen J, Olesen JB, e al.
Pso iasis is associa ed wi h clinically signi ican ca dio ascula isk: a Danish
na ionwide coho s udy. Jou nal o in e nal medicine. 2011;270(2):147-57.
10. Da ido ici BB, Sa a N, P inz J, Puig L, Eme y P, Ba ke JN, e al. Pso iasis and
sys emic in lamma o y diseases: po en ial mechanis ic links be ween skin disease and
co-mo bid condi ions. The Jou nal o in es iga i e de ma ology. 2010;130(7):1785-
96.
12
11. Neimann AL, Shin DB, Wang X, Ma golis DJ, T oxel AB, Gel and JM. P e alence o
ca dio ascula isk ac o s in pa ien s wi h pso iasis. Jou nal o he Ame ican
Academy o De ma ology. 2006;55(5):829-35.
12. Az a RS, Semina a NM, Shin DB, T oxel AB, Ma golis DJ, Gel and JM. Inc eased
isk o diabe es melli us and likelihood o ecei ing diabe es melli us ea men in
pa ien s wi h pso iasis. A chi es o de ma ology. 2012;148(9):995-1000.
13. Khalid U, Hansen PR, Gislason GH, Lindha dsen J, K is ensen SL, Win he SA, e al.
Pso iasis and new-onse diabe es: a Danish na ionwide coho s udy. Diabe es ca e.
2013;36(8):2402-7.
14. Li W, Han J, Hu FB, Cu han GC, Qu eshi AA. Pso iasis and isk o ype 2 diabe es
among women and men in he Uni ed S a es: a popula ion-based coho s udy. The
Jou nal o in es iga i e de ma ology. 2012;132(2):291-8.
15. A ms ong AW, Ha skamp CT, A ms ong EJ. The associa ion be ween pso iasis and
obesi y: a sys ema ic e iew and me a-analysis o obse a ional s udies. Nu i ion &
diabe es. 2012;2:e54.
16. B emme S, Van Voo hees AS, Hsu S, Ko man NJ, Lebwohl MG, Young M, e al.
Obesi y and pso iasis: om he Medical Boa d o he Na ional Pso iasis Founda ion.
Jou nal o he Ame ican Academy o De ma ology. 2010;63(6):1058-69.
17. Hamminga EA, an de Lely AJ, Neumann HA, Thio HB. Ch onic in lamma ion in
and obesi y: implica ions o he apy. Medical hypo heses. 2006;67(4):768-73.
18. Ha e KJ, Knop FK. Inc e in-based he apy and ype 2 diabe es. Vi amins and
ho mones. 2010;84:389-413.
19. Nishioka T, Shinoha a M, Tanimo o N, Kumagai C, Hashimo o K. Si aglip in, a
dipep idyl pep idase-IV inhibi o , imp o es pso iasis. De ma ology (Basel,
Swi ze land). 2012;224(1):20-1.
20. Lynch M, Tobin AM, Ahe n T, O'Shea D, Ki by B. Si aglip in o se e e pso iasis.
Clinical and expe imen al de ma ology. 2014;39(7):841-2.
21. D ucke DJ, Rosen CF. Glucagon-like pep ide-1 (GLP-1) ecep o agonis s, obesi y
and pso iasis: diabe es mee s de ma ology. Diabe ologia. 2011;54(11):2741-4.
22. Ahe n T, Tobin AM, Co igan M, Hogan A, Sweeney C, Ki by B, e al. Glucagon-like
pep ide-1 analogue he apy o pso iasis pa ien s wi h obesi y and ype 2 diabe es: a
p ospec i e coho s udy. Jou nal o he Eu opean Academy o De ma ology and
Vene eology : JEADV. 2013;27(11):1440-3.
13
23. Fau schou A, Gyldenlo e M, Rohde U, Thyssen JP, Zacha iae C, Sko L, e al. Lack
o e ec o he glucagon-like pep ide-1 ecep o agonis li aglu ide on pso iasis in
glucose- ole an pa ien s - a andomized placebo-con olled ial. Jou nal o he
Eu opean Academy o De ma ology and Vene eology : JEADV. 2014.
24. Buysschae M, Baeck M, P eumon V, Ma o L, Hend ickx E, Van Belle A, e al.
Imp o emen o pso iasis du ing glucagon-like pep ide-1 analogue he apy in ype 2
diabe es is associa ed wi h dec easing de mal gammadel a T-cell numbe : a
p ospec i e case-se ies s udy. The B i ish jou nal o de ma ology. 2014;171(1):155-
61.
25. Hogan AE, Tobin AM, Ahe n T, Co igan MA, Gaoa swe G, Jackson R, e al.
Glucagon-like pep ide-1 (GLP-1) and he egula ion o human in a ian na u al kille
T cells: lessons om obesi y, diabe es and pso iasis. Diabe ologia. 2011;54(11):2745-
54.
26. Fau schou A, Pede sen J, Gyldenlo e M, Poulsen SS, Hols JJ, Thyssen JP, e al.
Inc eased exp ession o glucagon-like pep ide-1 ecep o s in pso iasis plaques.
Expe imen al de ma ology. 2013;22(2):150-2.
27. Fau schou A, Knop FK, Thyssen JP, Zacha iae C, Sko L, Vilsboll T. Imp o emen in
pso iasis a e ea men wi h he glucagon-like pep ide-1 ecep o agonis li aglu ide.
Ac a diabe ologica. 2014;51(1):147-50.
28. Buysschae M, Tenns ed D, P eumon V. Imp o emen o pso iasis du ing exena ide
ea men in a pa ien wi h diabe es. Diabe es & me abolism. 2012;38(1):86-8.
29. Reid CT, Tobin AM, Ahe n T, O'Shea D, Ki by B. Li aglu ide in combina ion wi h
aci e in o se e e ecalci an pso iasis. The B i ish jou nal o de ma ology.
2013;169(1):230-1.
30. Cai Y, Fleming C, Yan J. De mal gammadel a T cells--a new playe in he
pa hogenesis o pso iasis. In e na ional immunopha macology. 2013;16(3):388-91.
31. Pe e nel S, Kas elan M. Immunopa hogenesis o pso iasis: ocus on na u al kille T
cells. Jou nal o he Eu opean Academy o De ma ology and Vene eology : JEADV.
2009;23(10):1123-7.
32. Came on AL, Ki by B, Fei W, G i i hs CE. Na u al kille and na u al kille -T cells in
pso iasis. A chi es o de ma ological esea ch. 2002;294(8):363-9.
33. Hossle EW, Ma oon MS, Mowad CM. Gas ic bypass su ge y imp o es pso iasis.
Jou nal o he Ame ican Academy o De ma ology. 2011;65(1):198-200.
14
34. Hossle EW, Wood GC, S ill CD, Mowad CM, Ma oon MS. The e ec o weigh loss
su ge y on he se e i y o pso iasis. The B i ish jou nal o de ma ology.
2013;168(3):660-1.
35. La e e e B. E ec o gas ic bypass su ge y on he inc e ins. Diabe es & me abolism.
2009;35(6 P 2):513-7.
36. Ming one G. Role o he inc e in sys em in he emission o ype 2 diabe es ollowing
ba ia ic su ge y. Nu i ion, me abolism, and ca dio ascula diseases : NMCD.
2008;18(8):574-9.
37. Fau schou A, Zacha iae C, Sko L, Vilsboll T, Knop FK. Gas ic bypass su ge y:
imp o ing pso iasis h ough a GLP-1-dependen mechanism? Medical hypo heses.
2011;77(6):1098-101.
15
FIGURES AND TABLES
Li e a u e sea ch
To al numbe o abs ac s iden i ied
om da abase sea ch (MEDLINE,
SCOPUS, Web o SCIENCE)
n = 84
Duplica ed a icles
(excluded n = 17)
To al numbe o a icles
n = 67
A icles sc eened on basis o i le
and abs ac s
(excluded 55)
Included n = 12
Manusc ip e iew and applica ion
o inclusion c i e ia
Included n = 8
Excluded n = 4
3 e iews
1 ench a icle

16
Diabe es and
Obesi y
Pso iasis
GLP-1
GLP-1 ecep o agonis s
Li aglu ide and Exena ide
- p olongs and enhances he e ec o GLP-1
- hey a e esis an o inac i a ion by DPP4
Gas ic Bypass Su ge y
- Roux-en-Y gas ic bypass p ocedu e: a small pa o
he s omach is used o c ea e a new s omach pouch; he
smalle s omach is connec ed di ec ly o he middle
po ion o he small in es ine (jejunum), bypassing he
es o he s omach and he uppe po ion o he small
in es ine (duodenum).
- educes body weigh
- imp o es glycaemic con ol
- imp o es PASI and DLQI
- dec eases numbe o de mal γδ T-
cells and IL-17 mRNA exp ession in
pso ia ic lesions
- inc eases ci cula ing iNKT cells
dec eases and plaque iNKT cells
- Inc eases GLP-1 le els
- Immedia ely imp o emen o
pso iasis be o e any weigh loss
Figu e 2. E ec s o GLP-1 ecep o agonis s and gas ic bypass su ge y in pso ia ic pa ien s wi h diabe es and obesi y
17
Table 1 S udy ou comes
S udy
S udy design
In e en ion
Pa icipan s
Va iables
Resul s
T. Ahe n e al,
2013
P ospec i e
coho s udy
10 weeks o li aglu ide he apy:
sel -adminis e ed by
subcu aneous injec ion; 0.6mg
daily o 2 weeks and 1.2mg daily
o 8 weeks
Pso iasis pa ien s wi h
diabe es and obesi y
(median age 48 yea s,
median BMI 48.2
Kg/m2)
n = 7
- PASI
- DLQI
- Ci cula ing iNKT
numbe
- Monocy e cy okine
p oduc ion
A week 10
- median PASI d opped om 4.8 (2.6–11.4) o 3.0
(1.9–7.9, P = 0.03)
- median DLQI d opped om 6 (3.5–8.9) o 2 (1–
6.1, P = 0.03)
- median ci cula ing iNKT cell pe cen age
inc eased 37.9% (18.5–234.6, P = 0.03)
- PBMC TNFα p oduc ion dec eased by a median
o 53%
A.Fau schou
e al, 2014
Randomized
placebo-
con olled
ial
Once-daily subcu aneous
injec ions wi h li aglu ide o
placebo, o 8 weeks; 0.6mg o 1
week, 1.2mg he ollowing week
and hen 1.8mg
Glucose- ole an and
obese pa ien s (BMI >
25 Kg/m2) wi h plaque
pso iasis
Placebo n = 9
Li aglu ide n = 11
- PASI
- DLQI
- Weigh
- hsCRP
- Ad e se e en s
A week 8
- mean PASI dec ease 2.6 ± 2.1 (mean ± SD,
P=0.026) in he li aglu ide g oup; non-signi ican
change in PASI in he placebo g oup (-1.3 ± 2.4,
P=0.141)
- no signi ican di e ences we e obse ed in he
DLQI
- he li aglu ide g oup had a significan loss in
bodyweigh compa ed wi h he placebo g oup
- no signi ican changes in hsCRP occu ed in
bo h g oups
- no majo ad e se e en s we e obse ed
M.Buysschae
e al, 2014
P ospec i e
case-se ies
Pa ien s sel -adminis e ed
subcu aneous injec ions wi h
exena ide (5µg wice daily) o
li aglu ide (0.6mg once a day o
1 week and hen 1.2mg once a
day).
The a iables we e measu ed a
baseline (T0) and 7±1 (T1) and
18±2 (T2) weeks a e ea men
wi h li aglu ide/exena ide.
Pa ien s wi h ype 2
diabe es and ch onic
pso iasis plaques
(mean age 56 ± 8
yea s, mean BMI 32.0
± 10.1 Kg/m2)
n = 7
- PASI
- BMI
- HbA1c
- de mal γδ T-cell
pe cen age
- IL-17 exp ession
- Pso iasis se e i y imp o ed wi h
li aglu ide/exena ide ea men (12.0±5.9 (T0),
9.2±6.2 (T1) and 9.2±6.4 (T2))
- BMI dec eased a e 4-5 mon hs o ea men
( om 32.0±10.1(T0) o 30.6±9.1 (T2) Kg/m2,
P=0.05)
- Glycaemic con ol imp o ed a T2 (HbA1c
dec eased om 7.5±1.2 (T0) o 6.5±0.8 (T2),
P=0.014)
- De mal γδ T-cell pe cen age was highe in
pso ia ic lesions compa ed wi h una ec ed skin
and a dec eased o 4.0±0.7% (P=0.05) occu ed in
he pa ien s wi h imp o ed (n=5) o unchanged
(n=1) PASI sco es du ing he ea men .
18
- No signi icance di e ence was seen du ing he
ea men in IL-17 exp ession.
Hogan e al,
2011
P ospec i e
s udy
Index pa ien : unde wen
ea men wi h exena ide o 2
mon hs and hen wi h li aglu ide.
O he pa ien s: wo addi ional
pa ien s s a ed li aglu ide o 6
weeks, a e he imp o emen o
pso ia ic lesions in he index
pa ien
Pa ien s wi h ype 2
diabe es and pso iasis
(n=2)
- PASI
- ci cula o y and
plaques le els o iNKT
cell
- GLP-1 ecep o
exp ession on iNKT
cells
- PASI imp o ed om 13.2 o 10.8 (pa ien 1)
and om 4.8 o 3.8 (pa ien 2)
- ci cula o y iNKT cell numbe inc eased a e he
ea men and plaque iNKT cell dec eased
- iNKT cells exp ess GLP-1R, which espond o
GLP-1 ac i a ing a signalling pa hway
Fau schou e
al, 2013
C oss-
sec ional
s udy
A skin biopsy was made e e y
heal hy olun ee and wo skin
biopsies e e y pso iasis pa ien s
( om a ec ed and una ec ed
skin). They collec ed a blood
sample om all pa icipan s and
cul u ed human ke a inocy es
we e s imula ed o uns imula ed.
Heal h olun ee s
(n=6) s Pso iasis
pa ien s (n=6)
- Exp ession o GLP-1
ecep o s in skin
biopsies, blood samples
and cul u ed human
ke a inocy es
- GLP-1 ecep o s we e exp essed in fi e o six
skin biopsies om pso iasis plaques, in one o six
biopsies om una ec ed pso ia ic skin and in one
o six biopsies om heal hy skin.
- GLP-1 ecep o s we e exp essed in he blood o
all pa icipan s.
- GLP-1 ecep o s exp ession we e no ound in
s imula ed o uns imula ed cul u ed human
ke a inocy es.
19
Table 2. Case epo s
S udy
Pa ien
Medical His o y
Physical examina ion
T ea men
Resul s
A.Fau schou e al,
2014
59 yea s
Man
- Type 2 diabe es (inadequa e
glycaemic con ol)
- Hype ension
- Hype choles e olemia
- Acu e myoca dial in a c ion
- Plaque pso iasis (diagnosed
15 yea s ago)
- BMI 29.3 kg/m2
- HbA1c 8.9% (74mmol/mol)
- Pso iasis was loca ed on he
elbows, knees, scalp, bu ocks
and do sal pa s o he hands
- Physician’s global assessmen
(PGA) sco e 3
- Li aglu ide: 0.6mg once
daily o 1 week and hen 1.2
mg once daily he ollowing 5
weeks and hen 1.8mg.
- Me o min: 1g wice a day
- Insulin??
A e 3 mon hs o ea men :
- HbA1c educed (5.9%)
- BMI 26.81 kg/m2
- Ad e se e en s - nausea and
headache, in e mi en
cons ipa ion and dia hoea. No
episodes o hypoglycaemia we e
epo ed
- Pso iasis symp oms imp o ed
- PGA educed (sco e 1)
M.Buysschae e
al, 2012
61 yea s
Man
- Type 2 diabe es o 14 yea s
- Hype ension
- Dyslipidaemia
- Pso iasis (since 1980)
- BMI 25.5 kg/m2
- HbA1c 8.1% (65mmol/mol)
- CRP 0.22 mg/dL
- PASI sco e 11
- Exena ide 2x5µg/day
(ini ia ed on Sep embe 2008)
- Me o min and
sulphonylu eas
- Pe indop il (5mg/day)
- Moxonidine (0.4mg/day)
- Sim as a in (20mg/day)
A e 12 mon hs o ea men :
- BMI 24.07 kg/m2
- HbA1c 7.3% (56mmol/mol)
- CRP 0.03 md/dL
- PASI sco e 3-4 (he s opped all
opical ea men s)
Exena ide ea men in e up ed
in Sep embe 2009:
- PASI sco e (a e 6 mon hs) >10
- weigh gain and wo sening o
glycaemic con ol (HbA1c 9.2%)
Ap il 2010, s a ed exena ide
ea men again:
- weigh loss
- HbA1c 8.1% (65mmol/mol)
- PASI sco e 3.1
Reid e al, 2013
54 yea s
Man
- Ex ensi e plaque pso iasis
- Malignan melanoma (wi hou
me as a ic disease)
- No diabe es
- BMI 42.1 kg/m2
- PASI 14.2
- DLQI 25
- Aci e in 50mg daily
- Li aglu ide (0.6mg daily o
one week and hen 3mg daily)
A e one yea :
- PASI 7.6
- DLQI 12
- Weigh dec eased 10kg
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