SUPPLEMENTARY DATA Electronic supplementary material (ESM) Tables

Supplementary Table 1. Additional information on the LTPA Questionnaire

The LTPA questionnaire used in the study is a Finnish conversion of the Minnesota Leisure Time Activity Questionnaire that was validated against double-labelled water [1]. The Finnish version is called the KIHD 12-month Leisure Time Physical Activity Questionnaire, and represents a detailed quantitative questionnaire assessing duration, frequency, and mean intensity of the most common lifestyle and structured LTPA in as recalled over the previous 12 months [2]. The KIHD questionnaire was validated in 1163 Finnish men from the general population with maximum oxygen uptake as the standard method validation [3]. The studies considering the questionnaire imply that it is representative and shows a relatively small intra-person variability. The 12-month LTPA correlated with the Vo2. [4]. The questionnaire contains a first section of questions of general type, frequency, duration, and intensity of LTPA. Information on general activity duration, frequency and intensity was used from the first section of the questionnaire. Additionally, a second section asks specific details on frequency (times per month), duration per session, and intensity for 21 types of predefined activities retrospectively from the past 12 months. Based on the intensity level (0-3), each of the 21 activities can be assigned a specific metabolic equivalent (MET) value: (1) conditioning physical activity-- walking (mean intensity, 4.2 MET), jogging (10.1 MET), skiing (9.6 MET), bicycling (5.8 MET), swimming (5.4 MET), rowing (5.4 MET), ball games (6.7 MET), and gymnastics, dancing, or weight lifting (5.0 MET); (2) nonconditioning physical activity -- crafts, repairs, or building (2.7 MET), yard work, gardening, farming, or snow shoveling (4.3 MET), hunting, picking berries, or gathering mushrooms (3.6 MET), fishing (2.4 MET), and forest activities (7.6 MET); and (3) walking (3.5 MET) or bicycling (5.1 MET) to work.

References

1. Slinde F, Arvidsson D, Sjoberg A et al. (2003) Minnesota leisure time activity questionnaire and doubly labeled water in adolescents. Med Sci Sports Exerc 35:1923-8 2. Lakka TA, Venalainen JM, Rauramaa R et al. (1994) Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of acute myocardial infarction. N Engl J Med 330:1549-54 3. Salonen J, Lakka T (1987) Assessment of physical activity in population studies: validity and consistency of the methods in the Kuopio ischemic heart disease risk factor study. Scand J Sports Sci 9:89–95 4. Lakka T, Salonen J (1992) Intra-person variability of various physical activity assessments in the Kuopio ischaemic heart disease risk factor study. Int J Epidemiol 21:467–472

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Supplementary Table 2. The 10-year cumulative incidence rates for cardiovascular mortality by total LTPA as well as exercise intensity, duration and frequency.

CVD death LTPA Intensity Frequency Duration (95% CI) 4.7% (3.2,6.2) 6.7% (4.7, 8.7) 5.5% (3.1, 7.9) 5.4% (2.6, 8.0) Low* N=731, 39 N= 530, 40 N=307, 19 N=256, 15 events events events events 1.9% (1.1,2.7) 1.9% (1.1,2.7) 2.8% (0.1, 5.4) 2.0% (1.2, 2.8) Moderate* N=1039, 25 N=1155, 32 N=146, 4 N=1072, 26 events events events events 1.8% (0.4,3.1) 0.2% (0.0, 0.6) 2.2% (1.4, 3.0) 2.7% (1.5, 3.8) High* N=404, 11 N=445, 1 N=1702, 50 N=689, 25 events event events events p value 0.001 <0.001 0.01 0.02 LTPA: Leisure-time physical activity CVD: cardiovascular disease. *LTPA: Low <10 METh/week; moderate 10–40 METh/week and high >40 METh/week. Intensity: low (no self-reported subjective shortness of breath and no sweating); moderate (a moderate degree of self-reported subjective shortness of breath and sweating); and high (a high degree of subjective shortness of breath and sweating). Duration: low: ≤30, moderate: 31-60 and high: >60 min/session. Frequency: low: <1, moderate: 1–2, and high: >2 sessions/week.

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Supplementary Table 3. Cox regression models showing HRs for low and moderate vs. high total LTPA, intensity, frequency and duration with respect to cardiovascular mortality.

CVD death, CVD death, CVD death, CVD death, HR(95% CI) HR(95% CI) HR(95% CI) HR(95% CI) LTPA Intensity Frequency Duration

Model 1: 2.15(1.10-4.20) 36.21(4.98-263.40) 2.18(1.29-3.70) 1.64(0.86-3.10) Low*, 0.90(0.44-1.83) 12.42(1.70-90.92) 0.93(0.34-2.57) 0.68(0.39-1.18) Moderate*, 1.00, N=2174, 1.00, N=2130, 73 1.00, N=2155, 1.00, N=2017, High* 75 events events 73 events 66 events

Model 2: Model 1+ gender, duration of 1.81(0.90-3.64) 12.51(1.69-92.91) 1.85(1.06-3.22) 1.19(0.61-2.31) diabetes, 1.13(0.54-2.40) 6.04(0.82-44.68) 1.30(0.46-3.66) 0.63(0.36-1.11) smoking, age 1.00, N=2125, 1.00, N= 2081, 69 1.00, N=2106, 1.00, N=1971, at onset of 71 events events 69 events 62 events diabetes, diabetic nephropathy

Model 3: 1.58(0.78-3.20) 10.41(1.39-77.88) 1.56(0.89-2.72) 1.18(0.61-2.30) Model 2 1.11(0.53-2.35) 5.77(0.78-42.87) 0.97(0.33-2.86) 0.72(0.40-1.28) +SBP, TG, 1.00, N=2090, 1.00, N=2046, 69 1.00, N=2071, 1.00, N=1940, BMI, HbA1c 71 events events 69 events 62 events

LTPA: Leisure-time physical activity. CVD: Cardiovascular disease SBP: systolic blood pressure. TG: triglycerides. * LTPA: Low <10 METh/week; moderate 10–40 METh/week and high >40 METh/week. Intensity: low (no self-reported subjective shortness of breath and no sweating); moderate (a moderate degree of self-reported subjective shortness of breath and sweating); and high (a high degree of subjective shortness of breath and sweating). Duration: low: ≤30, moderate: 31-60 and high: >60 min/session. Frequency: low: <1, moderate: 1–2, and high: >2 sessions/week.

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Supplementary Table 4. Cox regression models showing HRs for low and moderate vs. high total LTPA, intensity, frequency and duration with respect to all-cause mortality in men.

Mortality, Mortality, Mortality, Mortality, HR(95% CI) HR(95% CI) HR(95% CI) HR(95% CI) LTPA Intensity Frequency Duration

Model 1: 2.87(1.68-4.91) 9.08(4.84-17.00) 2.64(1.90-3.67) 2.42(1.53-3.81) Low*, 1.77(1.03-3.07) 3.52(1.85-6.69) 1.46(0.81-2.60) 1.33(0.89-1.99) Moderate*, 1.00, N=1150, 1.00, N=1120, 1.00, N=1141, 1.00, N=1046, High* 164 events 157 events 163 events 138 events

Model 2: Model 1+ duration of 2.48(1.43-4.30) 3.13(1.58-6.20) 2.29(1.62-3.23) 1.87(1.17-2.99) diabetes, 2.16(1.23-3.79) 1.66(0.83-3.29) 1.99(1.10-3.61) 1.06(0.71-1.61) smoking, age 1.00, N=1119, 1.00, N=1090, 1.00, N=1110, 1.00, N=1018, at onset of 159 events 153 events 158 events 134 events diabetes, diabetic nephropathy

Model 3: 2.45(1.38-4.35) 2.91(1.46-5.80) 2.03(1.41-2.92) 1.78(1.11-2.87) Model 2 2.26(1.27-4.05) 1.63(0.82-3.24) 1.85(1.02-3.35) 1.13(0.74-1.73) +SBP, TG, 1.00, N=1100, 1.00, N=1072, 1.00, N=1091, 1.00, N=1002, BMI, HbA1c 155 events 150 events 154 events 132 events

LTPA: Leisure-time physical activity. SBP: systolic blood pressure. TG: triglycerides. *LTPA: Low <10 METh/week; moderate 10–40 METh/week and high >40 METh/week. Intensity: low (no self-reported subjective shortness of breath and no sweating); moderate (a moderate degree of self-reported subjective shortness of breath and sweating); and high (a high degree of subjective shortness of breath and sweating). Duration: low: ≤30, moderate: 31-60 and high: >60 min/session. Frequency: low: <1, moderate: 1–2, and high: >2 sessions/week.

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Supplementary Table 5. Cox regression models showing HRs for low and moderate vs. high total LTPA, intensity, frequency and duration with respect to all-cause mortality in women.

Mortality, Mortality, Mortality, Mortality, HR(95% CI) HR(95% CI) HR(95% CI) HR(95% CI) LTPA Intensity Frequency Duration

Model 1: 2.09(1.23-3.55) 7.18(2.60-19.82) 2.96(1.91-4.60) 2.57(1.45-4.56) Low*, 0.62(0.35-1.11) 2.08(0.75-5.81) 0.54(0.17-1.72) 0.87(0.53-1.44) Moderate*, 1.00, N=1219, 1.00, N=1194, 1.00, N=1205, 1.00, N=1129, High* 106 events 100 events 101 events 86 events

Model 2: Model 1+ duration of 1.66(0.94-2.92) 2.44(0.87-6.88) 2.55(1.62-4.02) 2.03(1.13-3.65) diabetes, 0.66(0.36-1.22) 1.23(0.44-3.45) 0.66(0.21-2.12) 0.96(0.57-1.60) smoking, 1.00, N=1196, 1.00, N=1171, 96 1.00, N=1182, 1.00, N=1108, age at onset 102 events events 97 events 83 events of diabetes, diabetic nephropathy

Model 3: 1.43(0.81-2.54) 1.91(0.67-5.43) 2.18(1.36-3.51) 1.92(1.05-3.49) Model 2 0.66(0.36-1.21) 1.13(0.40-3.18) 0.50(0.14-1.70) 1.06(0.63-1.79) +SBP, TG, 1.00, N=1174, 1.00, N=1149, 94 1.00, N=1160, 1.00, N=1090, BMI, HbA1c 100 events events 95 events 82 events

LTPA: Leisure-time physical activity. SBP: systolic blood pressure. TG: triglycerides. *LTPA: Low <10 METh/week; moderate 10–40 METh/week and high >40 METh/week. Intensity: low (no self-reported subjective shortness of breath and no sweating); moderate (a moderate degree of self- reported subjective shortness of breath and sweating); and high (a high degree of subjective shortness of breath and sweating). Duration: low: ≤30, moderate: 31-60 and high: >60 min/session. Frequency: low: <1, moderate: 1–2, and high: >2 sessions/week.

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Supplementary Table 6. Cox regression models showing HRs for low vs. moderate/high* total LTPA, intensity, frequency and duration for all-cause mortality in patients with type 1 diabetes on dialysis.

Mortality, Mortality, Mortality, Mortality, HR(95% CI) HR(95% CI) HR(95% CI) HR(95% CI) LTPA Intensity Frequency Duration

Model 1: LTPA or 2.02(0.69-5.87) 1.45(0.51-4.10) 1.11(0.44-2.81) 1.87(0.59-5.87) intensity or N=36, 19 events N=34, 18 events N=36, 19 events N=27, 13 events frequency or duration Model 2: Model 1+ gender, duration of 3.05(0.73-12.83) 1.70(0.47-6.14) 1.31(0.40-4.26) 1.92(0.43-8.53) diabetes, N=35, 18 events N=33, 17 events N=35, 18 events N=27, 13 events smoking, age at onset of diabetes

Model 3: Model 2 2.16(0.36-13.19) 8.76(1.01-76.32) 2.99(0.67-13.37) 10.40(1.18-91.52) +SBP, TG, N=33, 16 events N=31, 15 events N=33, 16 events N=27, 13 events BMI, HbA1c

LTPA: Leisure-time physical activity. SBP: systolic blood pressure. TG: triglycerides. *LTPA: low <10 METh/week; moderate 10–40 METh/week and high >40 METh/week. Intensity: low (no self-reported subjective shortness of breath and no sweating); moderate (a moderate degree of self-reported subjective shortness of breath and sweating); and high (a high degree of subjective shortness of breath and sweating). Duration: low: ≤30, moderate: 31-60 and high: >60 min/session. Frequency: low: <1, moderate: 1–2, and high: >2 sessions/week.

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Supplementary Table 7. Cox regression models showing HRs for low vs. moderate/high* total LTPA, intensity, frequency and duration for all-cause mortality in patients with type 1 diabetes who have had a kidney transplant and whose eGFR is ≤60.

Mortality, Mortality, Mortality, Mortality, HR(95% CI) HR(95% CI) HR(95% CI) HR(95% CI) LTPA Intensity Frequency Duration

Model 1: LTPA or 1.99 (0.95-4.15) 3.11(1.31-7.38) 2.85(1.40-5.80) 4.03(1.80-9.01) intensity or N=64, 34 events N=60, 31 events N=63, 33 events N=52, 28 events frequency or duration Model 2: Model 1+ gender, duration of 2.12(0.99-4.57) 2.40(0.99-5.81) 2.60(1.15-5.84) 2.87(1.21-6.84) diabetes, N=63, 33 events N=60, 31 events N=62, 32 events N=51, 27 events smoking, age at onset of diabetes

Model 3: Model 2 2.08(0.87-4.97) 2.26(0.91-5.58) 3.36(1.30-8.65) 2.65(1.01-6.92) +SBP, TG, N=59, 30 events N=57, 29 events N=58, 29 events N=49, 25 events BMI, HbA1c

LTPA: Leisure-time physical activity. SBP: systolic blood pressure. TG: triglycerides. *LTPA: low <10 METh/week; moderate 10–40 METh/week and high >40 METh/week. Intensity: low (no self-reported subjective shortness of breath and no sweating); moderate (a moderate degree of self-reported subjective shortness of breath and sweating); and high (a high degree of subjective shortness of breath and sweating). Duration: low: ≤30, moderate: 31-60 and high: >60 min/session. Frequency: low: <1, moderate: 1–2, and high: >2 sessions/week.

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Supplementary Table 8. The Finnish Diabetic Nephropathy Study Centers

Anjalankoski Health Center S.Koivula, T.Uggeldahl Central Finland Central Hospital, Jyväskylä T.Forslund, A.Halonen, A.Koistinen, P.Koskiaho, M.Laukkanen, J.Saltevo, M.Tiihonen Central Hospital of Åland Islands, Mariehamn M.Forsen, H.Granlund, A.-C.Jonsson, B.Nyroos Central Hospital of Kanta-Häme, Hämeenlinna P.Kinnunen, A.Orvola, T.Salonen, A.Vähänen Central Hospital of Kymenlaakso, Kotka R.Paldanius, M.Riihelä, L.Ryysy Central Hospital of Länsi-Pohja, Kemi H.Laukkanen, P.Nyländen, A.Sademies Central Ostrobothnian Hospital District, Kokkola S.Anderson, B.Asplund, U.Byskata, P.Liedes, M.Kuusela, T.Virkkala City of Espoo Health Center: Espoonlahti A.Nikkola, E.Ritola Tapiola M.Niska, H.Saarinen Samaria E.Oukko-Ruponen, T.Virtanen Viherlaakso A.Lyytinen City of Health Center: H.Kari, T.Simonen A.Kaprio, J.Kärkkäinen, B.Rantaeskola Töölö P.Kääriäinen, J.Haaga, A-L.Pietiläinen City of Hyvinkää Health Center S.Klemetti, T.Nyandoto, E.Rontu, S.Satuli-Autere City of Health Center: Korso R.Toivonen, H.Virtanen Länsimäki R.Ahonen, M.Ivaska-Suomela, A.Jauhiainen Martinlaakso M.Laine, T.Pellonpää, R.Puranen Myyrmäki A.Airas, J.Laakso, K.Rautavaara Rekola M.Erola, E.Jatkola R.Lönnblad, A.Malm, J.Mäkelä, E.Rautamo Heinola Health Center P.Hentunen, J.Lagerstam Helsinki University Central Hospital, Department of M.Feodoroff, D.Gordin, O.Heikkilä, K.Hietala, Medicine, Division of Nephrology J.Fagerudd, M.Korolainen, K.Pettersson Fernholm, M.Rosengård-Bärlund, A.Sandelin, J.Tuomikangas Herttoniemi Hospital, Helsinki V.Sipilä Hospital of Lounais-Häme, Forssa T.Kalliomäki, J.Koskelainen, R.Nikkane, N.Savolainen, H.Sulonen, E.Valtonen Hyvinkää Hospital L. Norvio, A.Hämäläinen Iisalmi Hospita E.Toivanen Jokilaakso Hospital, Jämsä A.Parta, I.Pirttiniemi Jorvi Hospital, Helsinki University Central Hospital S.Aranko, S.Ervasti, R.Kauppinen-Mäkelin, A.Kuusisto, T.Leppälä, K.Nikkilä, L.Pekkonen Jyväskylä Health Center, Kyllö K.Nuorva, M.Tiihonen Kainuu Central Hospital, Kajaani S.Jokelainen, K.Kananen, M.Karjalainen, P.Kemppainen, A-M.Mankinen, A.Reponen Kerava Health Center M.Sankari Kirkkonummi Health Center H.Stuckey, P.Suominen Kivelä Hospital, Helsinki A.Lappalainen, M.Liimatainen, J.Santaholma Koskela Hospital, Helsinki A.Aimolahti, E.Huovinen Kotka Health Center V.Ilkka, M.Lehtimäki Kouvola Health Center E.Pälikkö-Kontinen, A.Vanhanen Kuopio University Hospital E.Koskinen, T.Siitonen E.Huttunen, R.Ikäheimo, P.Karhapää, P.Kekäläinen, M.Laakso, T.Lakka, E.Lampainen, L.Moilanen, S. Tanskanen L.Niskanen, U.Tuovinen, I.Vauhkonen, E.Voutilainen Kuusamo Health Center T.Kääriäinen, E.Isopoussu Kuusankoski Hospital E.Kilkki, I.Koskinen, L.Riihelä Laakso Hospital, Helsinki T.Meriläinen, P.Poukka, R.Savolainen, N.Uhlenius Lahti City Hospital A.Mäkelä, M.Tanner Lapland Central Hospital, Rovaniemi L.Hyvärinen, K.Lampela, S.Pöykkö, T.Rompasaari, S.Severinkangas, T.Tulokas Lappeenranta Health Center P. Erola, L.Härkönen, P.Linkola, T.Pekkanen, I.Pulli, E.Repo Lohja Hospital T.Granlund, K.Hietanen, M.Porrassalmi, M.Saari, T.Salonen, M.Tiikkainen Länsi- Hospital, Tammisaari I.-M.Jousmaa, J.Rinne

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1 SUPPLEMENTARY DATA Loimaa Health Center A.Mäkelä, P.Eloranta Malmi Hospital, Helsinki H.Lanki, S.Moilanen, M.Tilly-Kiesi Mikkeli Central Hospital A.Gynther, R.Manninen, P.Nironen, M.Salminen, T.Vänttinen Mänttä Regional Hospital I.Pirttiniemi, A-M.Hänninen North Karelian Hospital, Joensuu U-M.Henttula, P.Kekäläinen, M.Pietarinen, A.Rissanen,M.Voutilainen Nurmijärvi Health Center A.Burgos, K.Urtamo Oulaskangas Hospital, Oulainen E.Jokelainen, P-L.Jylkkä, E.Kaarlela, J.Vuolaspuro Oulu Health Center L.Hiltunen, R.Häkkinen, S.Keinänen-Kiukaanniemi Oulu University Hospital R.Ikäheimo Päijät-Häme Central Hospital H.Haapamäki, A.Helanterä, S.Hämäläinen,V.Ilvesmäki, H.Miettinen Palokka Health Center P.Sopanen, L.Welling Pieksämäki Hospital V.Sevtsenko, M.Tamminen Pietarsaari Hospital M-L.Holmbäck, B.Isomaa, L.Sarelin Pori City Hospital P.Ahonen, P.Merisalo, E.Muurinen, K.Sävelä Porvoo Hospital M.Kallio, B.Rask, S.Rämö Raahe Hospital A.Holma, M.Honkala, A.Tuomivaara, R.Vainionpää Rauma Hospital K.Laine, K.Saarinen, T.Salminen Riihimäki Hospital P.Aalto, E.Immonen, L.Juurinen Salo Hospital A.Alanko, J.Lapinleimu, P.Rautio, M.Virtanen Satakunta Central Hospital, Pori M.Asola, M.Juhola, P.Kunelius, M.-L.Lahdenmäki, P.Pääkkönen, M.Rautavirta Savonlinna Central Hospital T.Pulli, P.Sallinen, M.Taskinen, E.Tolvanen, T.Tuominen, H.Valtonen, A.Vartia, S-L.Viitanen Seinäjoki Central Hospital O.Antila, E.Korpi-Hyövälti, T.Latvala, E.Leijala, T.Leikkari, M.Punkari N.Rantamäki, H.Vähävuori South Karelia Central Hospital, Lappeenranta T.Ensala, E.Hussi, R.Härkönen, U.Nyholm, J.Toivanen Tampere Health Center A.Vaden, P.Alarotu, E.Kujansuu, H.Kirkkopelto- Jokinen, M.Helin, S.Gummerus, L.Calonius, T.Niskanen, T.Kaitala,v Tampere University Hospital P. Hannula, I.Ala-Houhala, R.Kannisto, T.Kuningas, P.Lampinen, M.Määttä, H.Oksala, T.Oksanen, A.Putila, H.Saha, K.Salonen, H.Tauriainen, S.Tulokas Tiirismaa Health Center, Hollola T.Kivelä, L.Petlin, L.Savolainen Turku Health Center A.Artukka, I.Hämäläinen, L.Lehtinen, E.Pyysalo, H.Virtamo, M.Viinikkala, M.Vähätalo Turku University Central Hospital K.Breitholz, R.Eskola, K.Metsärinne, U.Pietilä, P.Saarinen, R.Tuominen, S.Äyräpää Vaajakoski Health Center K.Mäkinen, P.Sopanen Valkeakoski Regional Hospital S.Ojanen, E.Valtonen, H.Ylönen, M.Rautiainen, T.Immonen Vammala Regional Hospital I.Isomäki, R.Kroneld, L.Mustaniemi, M.Tapiolinna- Mäkelä Vasa Central Hospital S.Bergkulla, U.Hautamäki, V-A.Myllyniemi, I.Rusk

©2017 American Diabetes Association. Published online at http://care.diabetesjournals.org/lookup/suppl/doi:10.2337/dc17-0615/-/DC1