Algorithm of the JJ Risk Engine

SUPPLEMENTARY DATA

Algorithm of the JJ risk engine. The JJ risk engine calculates t-year probabilities of fatal and non-fatal coronary heart disease, fatal and non-fatal stroke, non-cardiovascular mortality, overt nephropathy defined by persistent proteinuria and progression of retinopathy by inputting a covariate vector X and a time point for prediction t (i.e. the formula calculates 5-year probability if t=5) into the formula shown below. 2 Specifically, define X={sex (man=0, woman=1), age, HbA1C, years after diagnosis, BMI<18.5 kg/m (yes=1, no=0), BMI≥25 kg/m2 (yes=1, no=0), systolic blood pressure, non-high-density lipoprotein cholesterol, log-transformed urine albumin-to-creatinine ratio, atrial fibrillation (yes=1, no=0), current smoker (yes=1, no=0), leisure time physical activity (≥3.8METs-h/wk=1, otherwise=0) }. Let βjk be a vector of log hazard ratios for transition from state j to k; the state indexed by j=1…7 represent the initial state, presence of Stage 1 or 4 retinopathy, fatal and non-fatal coronary heart disease, fatal and non-fatal stroke, non-cardiovascular mortality, overt nephropathy defined by persistent proteinuria and progression of retinopathy, respectively. The states j=3…7 were assumed to be absorbing. The estimated hazard ratios for the JJ risk engine, exp(βjk), are provided in Table 1. Let λ0jk(t) be a baseline transition intensity for transition from state j to k. Then, the cause-specific transition intensity for a patient with covariate Xi is written as λijk(t)=λ0jk(t)exp(Xiβjk). Let Pijk(s, t) be the probability for the patient i of transition from state j to k during time interval between t and s. The t-year probability of state k is calculated by t u P1k (0,t) = exp{− ∑ λ1l (v)dv}{λ1k (u) + λ12 (u)P2k (u,t)}du ∫0 ∫0 l where j=1 denotes the initial state and j =2 denotes the state of Stage 1 or 4 retinopathy. Note that the t- year probability represents the probability of first occurrence of the kth event within t years and the t- year disease-free probability is obtained by . 1− (0, ) ∑k P1k t

The Japan Diabetes Complications Study (JDCS) Group Primary Investigators: Hirohito Sone, Nobuhio Yamada (University of Tsukuba); Chief in Assessment Committee: Yasuo Akanuma (Institute for Adult Diseases Asahi Life Foundation); Keita Ato, Masaaki Eto, Hiroshi Ito (Asahikawa Medical College), Naotake Hashimoto, Azuma Kanatsuka, Yasushi Saito, Kenichi Sakurai, Kazuo Takahashi, Kazuo Yagi, Kotaro Yokote (Chiba University), Tadami Takekoshi, Takanobu Wakasugi (Fukui Prefectural Hospital), Shigetake Toyooka (Fukui Red Cross Hospital), Yukihiro Bando (Fukui Saiseikai Hospital), Tsugihiko Nakai, Koji Oida, Jinya Suzuki (Fukui University), Yasuaki Fukumoto, Seiichi Sumi (Garatia Hostiptal), Tomokazu Awaya, Genshi Egusa, Rumi Fujikawa, Masamichi Okubo, Kiminori Yamane (Hiroshima University), Takao Koike, Narihito Yoshioka (Hokkaido University), Yasuo Akanuma, Motonobu Anai, Ritsuko Honda, Shoji Kawatsu, Masatoshi Kikuchi (Institute for Adult Diseases Asahi Life Foundation), Shun Ishibashi (Jichi Medical School), Masanobu Kawakami, Kazuyuki Namai, Hiroyuki Tamemoto, Hideo Toyoshima (Jichi Medical School Saitama Medical Center), Masami Nemoto, Takashi Sasaki (Jikei University),Ryuzo Kawamori, Yasushi Tanaka (Juntendo University), Toshihiko Ishida (Kagawa University), Toshihide Kawai, Izumi Takei (Keio University), Yoshikuni Fujita, Keiji Tanaka, Yoshihiro Yajima (Kitazato University), Noboru Furukawa, Hideki Kishikawa, Tetsushi Toyonaga, Kaku Tsuruzoe (Kumamoto University), Yoichi Imamura, Shingo Komichi, Zenji Makita, Kyohei Nonaka, Kentaro Yamada (Kurume University), Naoto Nakamura, Koji Nakano (Kyoto Prefectural University of Medicine), Toyoshi Iguchi, Hajime Nawata (Kyushu University), Yasuhisa Matsushima (Matsudo City Hospital), Hideo Takahashi (Minami Akatsuka Clinic), Hiroyuki Toyoshima (Minoh City Hospital), Shoichi Akazawa, Eiji Kawasaki, Shigenobu Nagataki (Nagasaki University), Toshio Hayashi, Nigishi Hotta, Jiro Nakamura (Nagoya University), Kentaro Doi, Yu Harano, Hisashi Makino, Yasunao Yoshimasa (National Cardiovascular Center), Yoichi Hayashi (Nihon University), Shinnichi Oikawa (Nippon

Medical School), Ryuzou Abe (Ohta Memorial Hospital),Hiroaki Seino, Susumu Suzuki, Daishiro Yamada (Ohta-Nishinouchi Hospital), Mitsuru Hoshi, Eiichi Imano, Takao Watarai (Osaka Koseinenkin Hospital), Masatoshi Imaizumi, Hideki Taki, Ryuhei Todo (Osaka National Hospital), Keisuke Kosugi, Yasuhisa Shimizu, Yutaka Umayahara (Osaka Police Hospital), Munehide Matsuhisa, Junichiro Miyagawa, Mitsuyoshi Nanba, Kohei Okita, Kaoru Takemura, Yoshimitsu Yamasaki (Osaka University), Yoshihito Atsumi, Kazuhiro Hosokawa, Kempei Matsuoka (Saiseikai Central Hospital), Junko Nakano, Hirotaka Umezu (Saiseikai Fukushima General Hospital), Akihiko Hoshino, Toshihiko Nishiyama, Tetsushi Nogami (Saisekai Kumamoto Hospital), Hideo Nunome (Saiseikai Mito Hospital), Shigehiro Katayama, Susumu Kurihara, Atsuhito Togashi (Saitama Medical College), Kenichi Yamada (Sakura National Hospital), Shinichi Araki, Atsunori Kashiwagi, Yoshihiko Nishio (Shiga University of Medical Science), Yukio Yoshimura (Shikoku University), Tatsuhide Inoue (Shizuoka General Hospital), Masafumi Kitaoka (Showa General Hospital), Toshio Kitada, Akio Shirai, Ryoichiro Watanabe (Takeda General Hospital), Takaichi Miyagawa (Tama Minami Clinic), Osamu Mokuta, Ryo Okazaki, Yoshikazu Sakamoto (Teikyo Universiy Ichihara Hospital), Yasushi Ishigaki, Kazuma Takahashi (Tohoku University),Yoh Miyashita, Koji Shirai (Toho University Sakura Hospital), Akira Tanaka (Tokyo Medical and Dental University), Yoshiaki Fujita (Tokyo Metropolitan Institute of Gerontology), Hideki Ito (Tokyo Metroporitan Geriatric Hospital) Yasuhiko Iwamoto, Reiko Kawahara, Yasue Omori, Asako Sato (Tokyo Women’s Medical University), Yasumichi Mori, Toshio Murase, Mitsuhiko Noda, Masato Odawara (Toranomon Hospital),Masashi Kobayashi, Masaharu Urakaze (Toyama University), Rei Aida, Hitomi Fujii, Satoshi Iimuro, Takashi Kadowaki, Yasuo Ohashi, Junichi Osuga, Yasuyoshi Ouchi, Akane Takahashi, Sachiko Tanaka, Shiro Tanaka (University of Tokyo), Hirohito Sone, Nobuhiro Yamada, Kamejiro Yamashita (University of Tsukuba), Ryo Kawasaki, Hidetoshi Yamashita (Yamagata University), Hisahiko Sekihara, Yasuo Terauchi (Yokohama City University), Tetsuo Nishikawa (Yokohama Rosai Hospital), Hiroto Furuta, Kishio Nanjo (Wakayama Medical University)

The Japanese Elderly Diabetes Intervention Trial (J-EDIT) Study Group Executive Committee: Hideki Ito (Chairman and Principal Investigator) , Atsushi Araki (Tokyo Metropolitan Geriatric Hospital), Atsunori Kashiwagi (Shiga University of Medical Science), Nobuhiro Yamada (University of Tsukuba), Koichi Yokono (University of Kobe), Takashi Sakurai, Hisayuki Miura (National Center for Geriatrics and Gerontology), Hiroyuki Umegaki (University of Nagoya), Kenzo Oba (Nippon Medical School), Katsuya Iijima (University of Tokyo), Tadasumi Nakano (Tokyo Metropolitan Tama Geriatric Hospital); Endpoint Committee: Kenzo Oba (Chairman; Nippon Medical School Hospital), Atsushi Araki (Tokyo Metropolitan Geriatric Hospital), Setsu Iijima (University of Tsukuba), Koichi Kozaki (Kyorin University), Teiko Yamamoto (University of Yamagata), Hiroshi Nakano (Nippon Medical School), Hirohito Sone (University of Tsukuba), Tadasumi Nakano (Tokyo Metropolitan Tama Geriatric Hospital), Yoshihiko Nishio (Shiga University of Medical Science), Kotaro Yokote (University of Chiba); Data and Safety Monitoring Committee: Kentaro Shimokado (Chairman; Tokyo Medical and Dental University), Yoichi Yazawa (Hokkaido National University of Education), Yasuo Ohashi (University of Tokyo); Data Management and Statistical Analysis Center: Yasuo Ohashi (Chairman), Satoshi Iimuro, Tomohiro Shinozaki (University of Tokyo); Nutritional Data Analysis Center: Yukio Yoshimura (Chairman), Chiemi Kamada, Keiko Takahashi (Shikoku University); Ophthalmological Data Analysis Center: Hidetoshi Yamashita (Chairman), Teiko Yamamoto (University of Yamagata); Clinical Centers where patients were registered and Investigators: Akizuki Morikawa (Asahikawa Red Cross Hospital), Shun Ishibashi (Jichi Medical University), Ryuzo Kawamori, Tomio Onuma (Juntendo University), Yuzo Mizuno, Mariko Miyao (Kanto Central Hospital of the Mutual Aid Association of Public School Teachers), Kouhei Kaku (Kawasaki Medical School), Hitoshi Ishida (Kyorin University), Hisayuki Miura (National Center for Geriatrics and Gerontology),

Masaaki Isaka, Seiji Suzuki (National Disaster Medical Center), Masahiro Nakano, Mototaka Yoshinari, Kenzo Iino, Masanori Wakisaka, Tamotsu Asano (National Fukuoka Higashi Hospital), Shozo Kobori, Tetsushi Toyonaga (National Kumamoto Hospital), Mitsurou Niinomi (National Nagoya Hospital), Yoshie Une, Masahiko Kato (National Nishi Sapporo Hospital), Kenzo Oba, Hiroshi Nakano (Nippon Medical School), Shinich Oikawa (Department of 3rd Internal Medicine, Nippon Medical School, Tokyo), Kiyoaki Seino, Susumu Suzuki (Ohta Nishinouchi Hosptal), Gyo Fujii, Toshihiko Sato (Osaka City General Hospital), Ryuichi Kikkawa, Atsunori Kashiwagi, Shin-ichi Araki, Yoshihiko Nishio (Shiga University of Medical Science), Kiyoshi Hashizume (Shinshu University), Tatsuhide Inoue (Shizuoka General Hospital), Hiroshi Tanaka (Social Insurance Chukyo Hospital), Takaichi Miyakawa (Tama Minami Clinic), Akio Ueno, Atsushi Ohno (Tokyo Medical University Hachioji Medical Center), Atsushi Araki, Seijiro Mori (Tokyo Metropolitan Geriatric Hospital), Tadasumi Nakano, Hideki Ito (Tokyo Metropolitan Tama Geriatric Hospital), Masato Odawara (Toranomon Hospital), Teruhiko Matsushima (Tsukuba Memorial Hospital), Nobuhiro Yamada, Hirohito Sone (Tsukuba University), Masaki Ito, Masafumi Kakei (University of Akita), Kotaro Yokote (University of Chiba), Koichi Yokono, Taichi Akisaki, Takashi Sakurai (University of Kobe), Akihisa Iguchi, Hiroyuki Umegaki (University of Nagoya), Hiroshi Ikegami, Tomomi Fujisawa, Yoshimitsu Yamazaki, Munehide Matsuhisa (University of Osaka), Nobuyuki Takasu (University of Ryukyus), Junya Ako, Koichi Kozaki, Katsuya Iijima, Junichi Osuga (University of Tokyo), Takeo Kato, Hideo Manaka, Makoto Daimon (University of Yamagata), Toru Tsunenari, Reiji Mimura (Wadayama Public Hospital), Kishio Nanjo (Wakayama Medical University)