11
Online Appendix 1 Abbreviation Description Unit Availability SOM input Adipon adiponectin mg/l 58% yes AHT anti-hypertensive treatment - 100% - ApoAI serum apolipoprotein A-I mg/dl 93% yes ApoAII serum apolipoprotein A-II mg/dl 89% no ApoB serum apolipoprotein B mg/dl 93% yes Chol total cholesterol mmol/l 97% yes CPept C-peptide pmol/l 76% no CRP C-reactive protein mg/l 82% yes DBP diastolic blood pressure mmHg 98% - DKD diabetic kidney disease * - 90% - DMDur duration of type 1 diabetes years 100% - DRP diabetic retinal disease - 99% - A1C glycosylated hemoglobin A 1c % 95% yes HDL 2 C high-density lipoprotein 2 cholesterol mmol/l 92% yes HDL 3 C high-density lipoprotein 3 cholesterol mmol/l 92% no LDLC LDL cholesterol (Friedewald) mmol/l 96% no MBL mannan binding lectin mg/l 59% yes MetS metabolic syndrome - 94% - SBP systolic blood pressure mmHg 98% - sCreat serum creatinine μmol/l 96% yes sK serum potassium mmol/l 55% yes sNa serum sodium mmol/l 55% yes TG triglyceride concentration mmol/l 97% yes 24h-uAlb 24h-urine albumin excretion mg 80% yes 24h-uCreat 24h-urine creatinine excretion mmol 66% yes 24h-uK 24h-urine potassium excretion mmol 62% no 24h-uNa 24h-urine sodium excretion mmol 62% no 24h-uUrea 24h-urine urea excretion mmol 61% no Only biochemical variables were included in the SOM input data. Furthermore, variables that were derived mathematically (Friedewald LDLC) or were strongly collinear with the other inputs (HDL 3 C, ApoAII, 24h-uK, 24h-uNa, 24h-uUrea) were excluded (the low avail- ability of the urine data caused additional artifacts in the analyses). C-peptide was close to the detection limit for almost all patients and was also excluded. SOM models that included all the biochemical variables were nevertheless tested to ensure that the model pruning did not reduce statistical sensitivity. Before analysis, the input data was rank-transformed for men and women separately. The robustness of the analyses was tested by removing patients with low availability of data; the results for the more complete subsets were consistent with the full dataset (not shown). In theory, the SOM algorithm is able to automatically ignore any missing values, but due to the PCA initialization (illustrated in Online Appendix 2), the preprocessed data was imputed by least-squares linear regression; this also ensured that the missing values did not cause any non-linear artifacts. * All patients were reviewed for DKD status, but 10% of the individuals could not be clas- sified due to inconclusive clinical data.

Online Appendix 1 - Diabetes

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Online Appendix 1

Abbreviation Description Unit Availability SOM inputAdipon adiponectin mg/l 58% yesAHT anti-hypertensive treatment - 100% -ApoAI serum apolipoprotein A-I mg/dl 93% yesApoAII serum apolipoprotein A-II mg/dl 89% noApoB serum apolipoprotein B mg/dl 93% yesChol total cholesterol mmol/l 97% yesCPept C-peptide pmol/l 76% noCRP C-reactive protein mg/l 82% yesDBP diastolic blood pressure mmHg 98% -DKD diabetic kidney disease∗ - 90% -DMDur duration of type 1 diabetes years 100% -DRP diabetic retinal disease - 99% -A1C glycosylated hemoglobin A1c % 95% yesHDL2C high-density lipoprotein 2 cholesterolmmol/l 92% yesHDL3C high-density lipoprotein 3 cholesterolmmol/l 92% noLDLC LDL cholesterol (Friedewald) mmol/l 96% noMBL mannan binding lectin mg/l 59% yesMetS metabolic syndrome - 94% -SBP systolic blood pressure mmHg 98% -sCreat serum creatinine µmol/l 96% yessK serum potassium mmol/l 55% yessNa serum sodium mmol/l 55% yesTG triglyceride concentration mmol/l 97% yes24h-uAlb 24h-urine albumin excretion mg 80% yes24h-uCreat 24h-urine creatinine excretion mmol 66% yes24h-uK 24h-urine potassium excretion mmol 62% no24h-uNa 24h-urine sodium excretion mmol 62% no24h-uUrea 24h-urine urea excretion mmol 61% no

Only biochemical variables were included in the SOM input data. Furthermore, variablesthat were derived mathematically (Friedewald LDLC) or werestrongly collinear with theother inputs (HDL3C, ApoAII, 24h-uK, 24h-uNa, 24h-uUrea) were excluded (the low avail-ability of the urine data caused additional artifacts in theanalyses). C-peptide was close tothe detection limit for almost all patients and was also excluded. SOM models that includedall the biochemical variables were nevertheless tested to ensure that the model pruning didnot reduce statistical sensitivity. Before analysis, the input data was rank-transformed formen and women separately.

The robustness of the analyses was tested by removing patients with low availability ofdata; the results for the more complete subsets were consistent with the full dataset (notshown). In theory, the SOM algorithm is able to automatically ignore any missing values,but due to the PCA initialization (illustrated in Online Appendix 2), the preprocessed datawas imputed by least-squares linear regression; this also ensured that the missing valuesdid not cause any non-linear artifacts.

∗All patients were reviewed for DKD status, but 10% of the individuals could not be clas-sified due to inconclusive clinical data.

Online Appendix 7

The Finnish Diabetic Nephropathy Study Centers

Anjalankoski health care center Sirpa KoivulaTarja Uggeldahl

Espoo health care center, Espoonlahti Anita NikkolaEila Ritola

Espoo health care center, Samaria Eija Oukko-RuponenEspoo health care center, Tapiola Hanna Saarinen

Merja Kataja-TuomolaMarjatta Niska

Espoo health care center, Viherlaakso Anne LyytinenSatu Raumavirta-KoivistoMarjo Kovanen

Etelä-Karjala Central Hospital Tuula EnsalaEsko HussiJukka ToivonenTuula MatikainenRaimo VanamoHelga Hasu

Heinola health care center Päivi HentunenJukka Lagerstam

Helsinki health care center, Puistola Kari PohjolaHeli SilvennoinenTiina SimonenHannele Kari

Helsinki health care center, Suutarila Anja KaprioBirgitta Rantaeskola

Helsinki health care center, Töölö Jari HaagaPirjo KääriäinenAnna-Liisa Pietiläinen

Helsinki Herttoniemi Hospital Markku SaraheimoKerstin Wickström

Helsinki University Central Hospital Paula NikkanenPirkko Salmi

Hyvinkää health care center Sisko KlemettiTeija NyandotoEija RontuSusanna Satuli-Autere

Iisalmi Hospital Eija ToivanenJaana Hyytiäinen

Jokilaakso Hospital Tuula LaitinenJukka Lagerstam

Jorvi Hospital Suvimarja ArankoTarmo LeppäläSuvi ErvastiRitva Kauppinen-MäkelinArto KuusistoKatriina NikkiläLeena Pekkonen

Jyväskylä health care center Kirsti NuorvaMarja Tiihonen

Järvenpää health care center Tuula KinnunenLiisa NikulainenTuula Salokangas

Kainuu Central Hospital Silja JokelainenPaula KemppainenAnna-Maria MankinenMarja Sankari

Online Appendix 7 2

Tuula MyllykangasKanta-Häme Central Hospital Pirjo Kinnunen

Anja OrvolaTapani SalonenAnnukka Vähänen

Kerava health care center Helene StuckeyPaula Suominen

Keski-Pohjanmaa Central Hospital Stefan AndersonBeatrice AsplundUlrika ByskataIngvor ByskataToini VirkkalaPäivi Liedes

Keski-Suomi Central Hospital Terje ForslundPirkko KoskiahoMarianne LaukkanenJuha SaltevoMarja TiihonenPirkko KoskiahoAnne HalonenArvo KoistinenEsa LeppänenAnna-Mari Koski

Kirkkonummi health care center Anja LappalainenMaisa LiimatainenJaana Santaholma

Kivelä Hospital, Helsinki Ari AimolahtiMaarit Kärki

Koskela Hospital, Helsinki Maija LehtimäkiNina UhleniusEeva HuovinenVeikko Ilkka

Kotka health care center Eeva Pälikkö-KontinenAnnika Vanhanen

Kouvola health care center Erkki KoskinenAnna BorgmanTaimi Siitonen

Kuopio University Central Hospital Erja HuttunenRisto IkäheimoPäivi KiljanderMarkku LaaksoTimo LakkaLeena MoilanenLeo NiskanenUlla TuovinenIlkka VauhkonenErkki VoutilainenPauli KarhapääPäivi KekäläinenErkki Lampainen

Kuusamo health care center Erja IsopoussuTapio KääriäinenEero Vierimaa

Kuusankoski Hospital Esa KilkkiLiisa Riihelä

Kymenlaakso Central Hospital Mare RiiheläLeena RyysyReino Paldanius

Laakso Hospital, Helsinki Taina MeriläinenPaula PoukkaTuula TikkanenRiitta Savolainen

Lahti City Hospital Aulikki MäkeläMarjukka TannerEija Behm

Länsi-Pohja Central Hospital Pirkko NyländenHilkka LaukkanenPirjo Myllykoski

Länsi-Uusimaa Hospital Inge-Maj JousmaaJukka Rinne

Lappeenranta health care center, Pirjo LinkolaArmila Hospital Irja Pulli

Lappi Central Hospital Sirkka SeverinkangasTimo Tulokas

Online Appendix 7 3

Liisa HyvärinenLohja Hospital Tuula Granlund

Mikko SaariTuula SalonenReija Tähtinen

Loimaa health care center Pirjo ElorantaArja Mäkelä

Lounais-Häme Hospital Tarja KalliomäkiJuha KoskelainenRiitta NikkanenVesa SalonenNiilo SavolainenHannu SulonenEija Valtonen

Malmi Hospital, Helsinki Helena LankiSeija MoilanenMarju Tilly-Kiesi

Mänttä Hospital Anne-Mirjami HänninenIsmo Pirttiniemi

Mikkeli Central Hospital Anita GyntherMaarit SalminenTuomo Vänttinen

Nurmijärvi health care center Mikko HonkasaloMarko MiettinenPäivi Nurminen

Oulaskangas Hospital Elina JokelainenPirkko-Liisa JylkkäElsi KaarlelaJari Vuolaspuro

Oulu health care center Rauni HäkkinenLiisa HiltunenSirkka Keinänen-Kiukaanniemi

Päijät-Häme Central Hospital Hannu HaapamäkiSatu HämäläinenAntero HelanteräVesa IlvesmäkiHilkka Miettinen

Tarja Tick-SinkkiläPalokka health care center, Palokka Leena WellingPalokka health care center, Vaajakoski Kirsti Mäkinen

Päivi SopanenPieksämäki Hospital Mari Tamminen

Markku TaskinenPietarsaari Hospital Maj-Len Holmbäck

Bo IsomaaLeena Sarelin

Pohjois-Karjala Central Hospital Laura HyttinenPäivi KekäläinenMaija PietarinenAnneli RissanenRisto LaitinenHannu TurtolaUlla Maija Henttula

Pori City Hospital Pirjo MerensaloKirsi SäveläTerttu ViitalaPäivi Ahonen

Porvoo Hospital Heidi JohanssonSirkka RämöBjarne RaskMarjatta Kallion

Raahe Hospital Anne HolmaMatti HonkalaAino TuomivaaraRiitta Vainionpää

Rauma Hospital Kaisa LaineTaru SalminenPaula KetolaKaisa Saarinen

Riihimäki Hospital Pirkko AaltoMarja LanniIrmeli LaitaharjuEija ImmonenLeena Juurinen

Online Appendix 7 4

Salo Hospital Jouni LapinleimuPirkko RautioMerja VirtanenAnita Alanko

Satakunta Central Hospital Markku AsolaPaavo PääkkönenMarjo PenttiMarja RautavirtaPertti KuneliusSirkku Mannila

Savonlinna Central Hospital Tuula PulliPäivi SallinenEija ToivanenHelena ValtonenAarne Vartia

Seinäjoki Central Hospital Eeva Korpi-HyövältiTerhikki LatvalaEsko LeijalaTarja Nyrhilä

Tammisaari Hospital Jukka RinneInge-Maj Jousma

Tampere health care center Pekka AlarotuLiisa CaloniusSeppo GummerusPaula HelinTarja KaitalaHelena Kirkkopelto-JokinenEila KujansuuTaru NiskanenAtte VadénTimo SaaristoMarjo KuorttiArja Kallio

Tampere University Central Hospital Ilpo Ala-HouhalaTuula KuningasPaula LampinenMarita Määttä

Heikki OksalaTuija OksanenKristiina SalonenSirkku TulokasHilkka Tauriainen

Tiirismaa health care center Leena PetlinLiisa SavolainenTiina Kivelä

Turku health care center Anne ArtukkaIrmeli HämäläinenPäivi KokkilaLea SorvariMarkku VähätaloHille Virtamo

Turku University Central Hospital Kaija BreitholzRaija EskolaKaj MetsärinneRiikka NevaUlla PietiläPirjo SaarinenRiitta TuominenMarkku AsolaSari Äyräpää

Vaajakoski health care center Päivi SopanenKirsti Mäkinen

Vaasa Central Hospital Stig BergkullaUlla HautamäkiVivi-Ann MyllyniemiIrma Rusk

Valkeakoski Hospital Terhi ImmonenSeppo OjanenMaisa RautiainenEija ValtonenHannu Ylönen

Vammala Hospital Irma IsomäkiLeena MustaniemiMerja Tapiolinna-Mäkela

Online Appendix 7 5

Riitta KroneldVantaa health care center, Korso Jaana Vahtola

Riitta ToivonenVantaa health care center, Länsimäki Raila Ahonen

Marja Ivaska-SuomelaAnu JauhiainenSari KulttiPirjo Kiviniemi

Vantaa health care center, Martinlaakso Merja LaineTiina PellonpääRiitta Puranen

Vantaa health care center, Myyrmäki Anne AirasJukka Laakso

Vantaa health care center, Rekola Matti EerolaEeva Jatkola

Vantaa health care center, Tikkurila Riitta LönnbladJari MäkeläAnita MalmElli Rautamo

Åland Central Hospital Hans GranlundAnn-Christin JohnssonMonica Forsen

Äänekoski health care center Satu SavolainenTapani Marjanen