Mul iple complica ions among people
wi h diabe es om Finland: an 18-yea
ollow-up in 1994–2011
E ja Fo ssas,
1
Ma i A man,
1
K is iina Mande backa,
1
Ilmo Keskimäki,
1,2
Ii is Ruu h,
1
Reijo Sund
3
To ci e: Fo ssas E,
A man M, Mande backa K,
e al. Mul iple complica ions
among people wi h diabe es
om Finland: an 18-yea
ollow-up in 1994–2011.
BMJ Open Diabe es Resea ch
and Ca e 2016;4:e000254.
doi:10.1136/bmjd c-2016-
000254
P elimina y esul s o he
s udy ha e been p esen ed in
pos e o m in Eu opean
Public Heal h Cong ess in
Glasgow, Sco land, 19–22
No embe 2014.
Recei ed 21 Ap il 2016
Re ised 25 Augus 2016
Accep ed 16 Sep embe 2016
1
Se ice Sys em Resea ch
Uni , Na ional Ins i u e o
Heal h and Wel a e, Helsinki,
Finland
2
School o Heal h Sciences,
Uni e si y o Tampe e,
Tampe e, Finland
3
Cen e o Resea ch
Me hods, Uni e si y o
Helsinki, Helsinki, Finland
Co espondence o
Ma i A man;
[email p o ec ed]
ABSTRACT
Objec i e: In his s udy, we examined ends in se e e
diabe es- ela ed complica ions (acu e myoca dial
in a c ion, s oke, lowe ex emi y ampu a ion, and end-
s age enal disease) and p e alence o mul iple
complica ions in a o al popula ion wi h diabe es in
Finland du ing an 18-yea pe iod.
Resea ch design and me hods: The o al
popula ion wi h diabe es aged 30 yea s o olde in
1994–2011 was ob ained om se e al Finnish heal h
egis e s. Only he i s episode o each end poin was
included in he analysis. We examined ends in he
p e alence o hese end poin s using age-
s anda diza ion and changes in hese end poin s we e
analyzed using epea ed-measu es Poisson eg ession
models.
Resul s: The p e alence o single como bidi ies
dec eased du ing he s udy pe iod, especially o acu e
myoca dial in a c ion and s oke. The age-adjus ed and
diabe es du a ion-adjus ed isk o ha ing one o hese
end poin s dec eased h oughou he s udy pe iod
among pe sons wi h ype 2 diabe es. Among women,
he isk a io was 0.71 (0.63 o 0.79) in 2006–2011
compa ed o 1994–1999, and among men, he igu e
was 0.72 (0.66 o 0.78). In ype 1 diabe es, he isk o
mul iple se ious complica ions inc eased. We u he
ound inc eased mo ali y isk among pe sons wi h any
o hese complica ions i espec i e o diabe es ype.
Conclusions: Ou esul s conce ning he de elopmen
o isk o complica ions sugges imp o emen s in he
managemen o diabe es. Mo e a en ion needs o be
paid o he p e en ion o complica ions among olde
pe sons and hose wi h longe his o y o diabe es o
p e en clus e ing o complica ions and o p e en he
diabe es epidemic in he popula ion o educe he
public heal h bu den o diabe es.
INTRODUCTION
Popula ion wi h diabe es is g owing wo ld-
wide due o an epidemic o ype 2 diabe es
12
and an inc ease in he incidence o ype 1
diabe es.
23
Fu he , imp o emen s in he
diagnos ic me hods and ea lie de ec ion o
diabe es as well as imp o emen s in diabe es
ca e inc easing he li e expec ancy o
pa ien s wi h diabe es ha e had an e ec .
Diabe es equi es con inuous medical a en-
ion, including mul i ac o ial isk educ ion,
suppo ing pa ien sel -managemen , p e en-
ion o acu e complica ions, and educ ion o
he isk o long- e m complica ions.
4
The
main bu den o popula ion heal h and
heal hca e comes om i s mic o ascula and
mac o ascula complica ions.
5
While he e is a g owing li e a u e con-
ce ning mul imo bidi y in gene al including
Signi icance o his s udy
Wha is al eady known abou his subjec ?
▪The e is a g owing li e a u e conce ning mul i-
mo bidi y in gene al including also diabe es and
conce ning single complica ions o diabe es. The
s udies show ha he main bu den o popula ion
heal h and heal hca e comes om i s mic o-
ascula and mac o ascula complica ions.
Wha a e he new indings?
▪Ou esul s show a ma ked dec ease in isk o
one se ious complica ion du ing he s udy
pe iod among pe sons wi h ype 2 diabe es,
mainly d i en by dec ease o acu e myoca dial
in a c ion and s oke among pe sons wi h
diabe es.
▪Howe e , acco ding o ou esul s, he isk o
mul iple complica ions did no dec ease among
pe sons wi h ype 1 diabe es. This is likely o be
associa ed wi h aging o he diabe es popula ion
and wi h ad ances in ca e inc easing he likeli-
hood o su i al wi h complica ions.
How migh hese esul s change he ocus o
esea ch o clinical p ac ice?
▪An impo an ques ion o u u e s udies is
whe he he e ha e been ac ual imp o emen s in
he p e en ion o complica ions among pe sons
wi h al eady exis ing diabe es.
▪Mo e a en ion needs o be paid o he p e en-
ion o complica ions among olde pe sons and
hose wi h longe his o y o diabe es o p e en
clus e ing o mul iple complica ions and o p e-
en ion o diabe es epidemic in he popula ion o
educe he public heal h bu den o diabe es.
BMJ Open Diabe es Resea ch and Ca e 2016;4:e000254. doi:10.1136/bmjd c-2016-000254 1
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also diabe es,
6–8
and conce ning single complica ions o
diabe es,
9–14
s udies in es iga ing how se e al complica-
ions o diabe es clus e among indi iduals ha e mainly
examined complica ions as pa o a b oade amewo k
o mul imo bidi y and ha e mainly been based on
egional samples.
15 16
The aim o his s udy was o examine ends in acu e
myoca dial in a c ion (AMI), s oke, lowe ex emi y
ampu a ion, and end-s age enal disease (ESRD) ep e-
sen ing impo an complica ions o diabe es among
people aged 30 yea s o olde in a o al popula ion wi h
diabe es in Finland be ween 1994 and 2011.
RESEARCH DESIGN AND METHODS
Popula ion wi h diabe es
The popula ion wi h diabe es was defined as hose
ha ing any diabe es- ela ed en ies in any o he ollow-
ing egis e s: he Hospi al Discha ge Regis e , he Cause
o Dea h Regis e , he Finnish Kidney Regis e , and d ug
egis e s o he Social Insu ance Ins i u ion be ween
1964 and 2011 and ali e in 1 Janua y 1994. Fo hese
pe sons, in o ma ion ega ding he use o hospi al se -
ices and causes o dea h was indi idually linked using
he pe sonal iden ifica ion code unique o each indi id-
ual. Diabe es ype was de e mined by egis e en ies
conce ning d ug use: pe sons ha ing en ies on con inu-
ous use o insulin bu no signs o d ug use inc easing
insulin p oduc ion o he panc eas we e defined as
ha ing ype 1 diabe es. Popula ion a isk was defined as
pe sons wi h diabe es aged 30 yea s o olde in 1994–
2011. We o med annual coho s o all indi iduals wi h
diabe es and ali e in he beginning o he yea and
hose wi h inciden diabe es du ing ha yea . Since we
examined complica ions o diabe es, he diabe es diag-
nosis needed o p ecede he complica ion en y. Pe sons
wi h ges a ional diabe es only we e excluded om he
analyses.
Diabe es- ela ed complica ions we e defined as igh
o ele a ed heal h insu ance eimbu semen o d ug
cos s due o each o hese complica ions g an ed by he
Social Insu ance Ins i u ion, o an en y in he Hospi al
Discha ge Regis e , o Cause o Dea h Regis e o he
Finnish Kidney Regis e . We examined he ollowing
complica ions: (1) s oke (ICD-9 and ICD-10 codes:
430*, 431*, 4330A, 4331A, 4339A, 4340A, 4341A, 4349A,
I60*, I61*, I63*), (2) AMI (ICD-9 and ICD-10 codes:
410*, I21*–I22*), (3) lowe ex emi y ampu a ion (LEA)
(Finnish Hospi al League codes: 9571–9575, NOMESCO
codes: NFQ10, NFQ20, NGQ10, NGQ20, NHQ10,
NHQ20, NHQ30, o NHQ40), and (4) ESRD (en y in
he Finnish Kidney Regis e conce ning he onse o
enal eplacemen he apy o cause o dea h codes 5855,
5856, N185, o N186). We examined he fi s egis e
en y o each complica ion only as hey a e ch onic con-
di ions. By only coun ing he fi s egis e en y, we
wan ed o ensu e no coun ing he same complica ion
se e al imes as each o he complica ions can esul o
en ies in di e en egis e s and se e al en ies in he
hospi al discha ge egis e .
S a is ical analyses
We examined ends in he p e alence o hese compli-
ca ions by calcula ing age-s anda dized a es pe 1000
using he 2011 diabe es popula ion as a s anda d.
Mul i a ia e analyses we e based on epea ed-measu es
Poisson eg ession models con olling o age and dia-
be es du a ion. Sepa a e models we e calcula ed o
men and women. T ends in he clus e ing o complica-
ions we e analyzed by compa ing p e alence in 1994–
1999 o wo la e pe iods (2000–2005 and 2006–2011).
We u he examined in e ac ions be ween age and
pe iod as well as du a ion o diabe es and pe iod o
s udy whe he he de elopmen was simila in di e en
subg oups. In addi ional analyses, we conduc ed Cox
eg ession models using coun ing p ocess da a o s udy
he e ec o he ou complica ions on su i al un il
dea h o censo ing a he end o yea 2011. Models we e
fi ed o people wi h ype 1 and ype 2 diabe es sepa -
a ely and adjus ed o gende , age, s udy pe iod, and
du a ion o diabe es. E hical app o al o he s udy was
ecei ed om he Resea ch E hics Commi ee o he
Na ional Ins i u e o Heal h and Wel a e.
RESULTS
The e we e al oge he 145 738 pe sons wi h diabe es in
1994. The popula ion wi h diabe es inc eased apidly
du ing he s udy pe iod ( able 1) as did he p opo ion
o men in he popula ion. Mo e han 80% o he popu-
la ion had ype 2 diabe es in 1994 and he p opo ion
inc eased o 90% du ing he s udy pe iod. The mean
du a ion o diabe es was longe owa d he end o he
Table 1 Basic backg ound cha ac e is ics o he
popula ion wi h diabe es in 1994 and 2011 in Finland
Yea 1994 2011
n 145 738 342 028
%%
Gende
Male 44 51
Female 56 49
Diabe es ype
Type 1 17 10
Type 2 83 90
Age (yea s)
30–44 10 7
45–64 31 35
65–74 28 28
75–84 23 21
85+ 9 9
Diabe es du a ion (mean (SD))
Type 1 15.7 (9.0) 20.3 (14.4)
Type 2 6.3 (6.7) 7.3 (7.2)
2BMJ Open Diabe es Resea ch and Ca e 2016;4:e000254. doi:10.1136/bmjd c-2016-000254
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s udy pe iod among ype 1 and ype 2 diabe es
popula ion.
Figu e 1 p esen s age-s anda dized ends in each
complica ion examined om 1994 o 2011 by diabe es
ype. AMI and s oke we e common among bo h pa ien
g oups. Whe eas AMI a es dec eased du ing he s udy
pe iod by a hi d among pa ien s wi h ype 2 diabe es
and by a ou h among pa ien s wi h ype 1 diabe es, he
decline in s oke was 21% among pe sons wi h ype 2
diabe es and only 5% among hose wi h ype 1 diabe es.
LEA a es we e much highe among pe sons wi h ype 1
diabe es and emained on he same le el h oughou
he s udy pe iod, bu dec eased by almos 50% among
hose wi h ype 2 diabe es. ESRD a es we e much
highe among pe sons wi h ype 1 diabe es and
emained simila h oughou he s udy pe iod among
bo h pa ien g oups.
Since he p e alence o mos complica ions s udied
dec eased in ime, we examined he isk o
co-occu ence o one and o se e al complica ions wi h
diabe es adjus ed o age and du a ion o diabe es, in
h ee ime pe iods compa ing yea s 2000–2005 and
2006–2011 o he beginning o he s udy pe iod (1994–
1999) by diabe es ype ( able 2). The isk o ha ing one
complica ion emained on app oxima ely he same le el
o pe sons wi h ype 1 diabe es among men and
women h oughou he s udy pe iod. Among pe sons
wi h ype 2 diabe es, he isk o ha ing one complica ion
dec eased s eadily du ing he s udy pe iod among bo h
gende s. The isk o ha ing wo o mo e complica ions
inc eased by >25% om 1994–1999 o he beginning o
he 2000s among men and women wi h ype 1 diabe es
and emained on he same le el a e ha . Among
pe sons wi h ype 2 diabe es, he isk o ha ing wo o
mo e complica ions diminished especially owa d he
end o he s udy pe iod.
We hen examined whe he he de elopmen in ime
was simila among di e en age g oups and by diabe es
du a ion. No significan in e ac ions we e ound among
ei he men o women wi h ype 1 diabe es. Howe e , he
isk o ha ing one complica ion among pe sons wi h
ype 2 diabe es and he isk o ha ing wo complica ions
among men we e significan ly mo e p onounced among
olde pe sons (all p alues <0.05) and hose wi h longe
Figu e 1 The p e alence o complica ions (pe 1000) among pe sons wi h diabe es in 1994–2011 in Finland by diabe es ype.
AMI, acu e myoca dial in a c ion; ESRD, end-s age enal disease; LEA, lowe ex emi y ampu a ion.
Table 2 Change in age-s anda dized isk o mul iple complica ions among pe sons wi h diabe es aged 30 yea s o olde in
2000–2005 and 2006–2011 compa ed o pe iod 1994–1999 (1.00), isk a ios, and hei 95% CIs con olling o diabe es
du a ion
Type 1 Type 2
2000–2005 2006–2011 2000–2005 2006–2011
Women
1 complica ion 1.06 (1.01 o 1.12)* 1.00 (0.94 o 1.07) 0.89 (0.80 o 0.98)* 0.71 (0.63 o 0.79)***
≥2 complica ions 1.31 (1.14 o 1.50)*** 1.27 (1.09 o 1.47)** 0.96 (0.80 o 1.16) 0.72 (0.59 o 0.89)***
Men
1 complica ion 1.00 (0.95 o 1.05) 0.95 (0.90 o 1.00)* 0.89 (0.83 o 0.96)** 0.72 (0.66 o 0.78)***
≥2 complica ions 1.26 (1.10 o 1.43)*** 1.23 (1.08 o 1.40)** 1.09 (0.95 o 1.26) 0.84 (0.72 o 0.97)*
*p<0.05, **p<0.01, ***p<0.001.
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du a ion o diabe es (all p alues <0.01) owa d he end
o he s udy pe iod.
We u he analyzed excess mo ali y isk associa ed
wi h hese complica ions. Significan ly inc eased mo al-
i y isk was ound o each o he complica ions s udied
among pe sons wi h ype 1 and ype 2 diabe es ( able 3).
The mo ali y isk was highes and mo e han h ee old
among pe sons wi h AMI o ESRD i espec i e o dia-
be es ype.
CONCLUSIONS
O e iew o main esul s
This egis e -based s udy ollowed pe sons aged 30 yea s
and olde wi h diabe es h ough an 18-yea pe iod and
examined he p e alence o ou complica ions o dia-
be es. While AMI and s oke a es we e on simila le el
ega dless o diabe es ype, LEA and ESRD we e much
mo e common among pe sons wi h ype 1 diabe es.
Addi ionally, complica ion a es dec eased less among
pe sons wi h ype 1 diabe es du ing he s udy pe iod.
The dec ease in LEA a es among pe sons wi h ype 2
diabe es is in line wi h ea lie esul s sugges ing dec eas-
ing ampu a ion a es among pe sons wi h diabe es in
Finland
13
and elsewhe e.
11
Addi ionally, AMI and s oke
a es dec eased in bo h pa ien g oups in line wi h
ea lie esul s.
915
The isk o one se ious complica ion
dec eased du ing he s udy pe iod among pe sons wi h
ype 2 diabe es sugges ing ad ances in seconda y p e en-
ion. Howe e , pa o he dec ease especially among
pe sons wi h ype 2 diabe es is likely o be due o
imp o emen s in ea ly diagnosis o he disease inc eas-
ing he numbe o pe sons wi h a milde s age o disease
in he popula ion. The isk o mul iple complica ions
did no dec ease among pe sons wi h ype 1 diabe es,
which is likely o be due o aging o he diabe es popula-
ion and ad ances in medical ca e inc easing he likeli-
hood o su i al wi h complica ions. Ne e heless, we
s ill ound inc eased mo ali y isk among pe sons wi h
any o hese complica ions. The mo ali y isk was
highes among pe sons wi h AMI and ESRD.
Me hodological conside a ions
Ou esea ch da a and indica o s o complica ions we e
based on se e al la ge adminis a i e egis e s he alidi y
o which has, in gene al, been es ima ed o be good.
17 18
As AMI, s oke, LEA, and ESRD a e se ious condi ions
no ea ed in ambula o y ca e, mos cases a e likely o
be cap u ed by he egis e s used in he cu en s udy. A
limi a ion o ou s udy is ha we could no examine e -
inopa hy, since comp ehensi e egis e da a conce ning
i do no exis in Finland. Ou da a on d ug use we e
based on eimbu semen da a o ac ual d ug cos s and
en i lemen s o ele a ed eimbu semen o d ug cos s
based on s anda dized diagnos ic c i e ia; alse-posi i e
cases a e he e o e likely o be a e. Ou esul s co e
complica ions among pe sons wi h diabe es diagnosed
in he heal hca e sys em and ea ed wi h d ugs, as hose
wi h diabe es ea ed wi h die only could no be iden i-
fied om he egis e s. Ou da a se has, howe e , been
shown o ha e ela i ely good co e age in compa ison o
a local diabe es egis e om he Me opoli an a ea.
19
Defini ion o diabe es ype using egis e da a only is a
challenge, and ou defini ion was based on ac ual d ug
pu chases among pe sons wi h diabe es. We could no
examine he po en ial imp o emen s made in ambula-
o y ca e in he p e en ion o complica ions sugges ed
by ou esul s, since Finnish egis e s do no cu en ly
co e compa able da a conce ning ambula o y se ice
use o clinical con en o ca e o he whole coun y.
Conclusions
Ou esul s sugges imp o emen s in he managemen o
diabe es, bu he e a e s ill pa ien g oups among whom
mo e a en ion needs o be paid o mul i ac o ial man-
agemen o isk ac o s (glucose le el, blood p essu e,
lipid le el, smoking) in o de o a oid se ious complica-
ions and clus e ing o mul iple complica ions.
20
Mo e
a en ion needs o be paid o he p e en ion o complica-
ions among olde pe sons and hose wi h longe his o y
o diabe es o p e en clus e ing o mul iple complica-
ions and o p e en ion o diabe es epidemic in he popu-
la ion o educe he public heal h bu den o diabe es.
Acknowledgemen s The au ho s would like o hank he Finnish Diabe es
Associa ion and he Social Insu ance Ins i u ion o collabo a ion in he
o ming o he da a se .
Con ibu o s EF con ibu ed o he concep ion and design o he s udy,
planning and execu ing o analyses, and d a ed he manusc ip . MA
con ibu ed o he concep ion and design o he s udy, he s a is ical analyses,
and ook pa in he e ision o he manusc ip o impo an in ellec ual
con en . KM con ibu ed o he concep ion o he s udy and in e p e a ion o
he esul s and ook pa in he e ision o he manusc ip o impo an
in ellec ual con en . IR con ibu ed o he concep ion and design o he s udy,
o ming he da a, and ook pa in he e ision o he s udy. IK and RS
con ibu ed o he concep ion and design o he s udy, planning o analyses,
and ook pa in he e ision o he manusc ip o impo an in ellec ual
con en . RS ac s as a gua an o o he pape . All au ho s ha e ead and
app o ed he inal manusc ip .
Table 3 Mo ali y isk among pe sons wi h diabe es in
1994–2011 by diabe es ype (HRs and hei 95% CIs
con olling o gende , age, pe iod, diabe es du a ion, and
all s udied complica ions)
Type 1 Type 2
Complica ion HR 95% CI HR 95% CI
S oke 2.23*** 2.13 o
2.34
2.25*** 2.22 o
2.28
AMI 3.88*** 3.72 o
4.04
3.35*** 3.31 o
3.40
LEA 2.17*** 2.05 o
2.29
2.11*** 2.06 o
2.17
ESRD 3.13*** 2.90 o
3.39
3.05*** 2.84 o
3.28
***p<0.001.
AMI, acu e myoca dial in a c ion; ESRD, end-s age enal disease;
LEA, lowe ex emi y ampu a ion.
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Funding This wo k was suppo ed by he Academy o Finland (p ojec s
numbe 277 939 and 254 121).
Disclaime The Academy o Finland had no in ol emen in i s design, da a
collec ion, indings, o decision o publish.
Compe ing in e es s None decla ed.
E hics app o al The Resea ch E hics Commi ee o THL.
P o enance and pee e iew No commissioned; ex e nally pee e iewed.
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BMJ Open Diabe es Resea ch and Ca e 2016;4:e000254. doi:10.1136/bmjd c-2016-000254 5
Epidemiology/heal h se ices esea ch
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2011−in 1994 diabe es om Finland: an 18-yea ollow-up
Mul iple complica ions among people wi h
Ruu h and Reijo Sund
E ja Fo ssas, Ma i A man, K is iina Mande backa, Ilmo Keskimäki, Ii is
doi: 10.1136/bmjd c-2016-000254
2016 4: BMJ Open Diab Res Ca e
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