Multiple complications among people with diabetes from Finland: an 18-year follow-up in 1994-2011

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 Open Access Resea ch g oup.bmj.com on No embe 9, 2016 - Published by h p://d c.bmj.com/Downloaded om 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 Epidemiology/heal h se ices esea ch g oup.bmj.com on No embe 9, 2016 - Published by h p://d c.bmj.com/Downloaded om 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. BMJ Open Diabe es Resea ch and Ca e 2016;4:e000254. doi:10.1136/bmjd c-2016-000254 3 Epidemiology/heal h se ices esea ch g oup.bmj.com on No embe 9, 2016 - Published by h p://d c.bmj.com/Downloaded om 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. 4BMJ Open Diabe es Resea ch and Ca e 2016;4:e000254. doi:10.1136/bmjd c-2016-000254 Epidemiology/heal h se ices esea ch g oup.bmj.com on No embe 9, 2016 - Published by h p://d c.bmj.com/Downloaded om 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. 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E ec o a mul i ac o ial in e en ion on mo ali y in ype 2 diabe es. N Engl J Med 2008;358:580–91. 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 g oup.bmj.com on No embe 9, 2016 - Published by h p://d c.bmj.com/Downloaded om 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 h p://d c.bmj.com/con en /4/1/e000254 Upda ed in o ma ion and se ices can be ound a : These include: Re e ences #BIBLh p://d c.bmj.com/con en /4/1/e000254 This a icle ci es 20 a icles, 6 o which you can access o ee a : Open Access h p://c ea i ecommons.o g/licenses/by-nc/4.0/non-comme cial. 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