Supplementary Data

SUPPLEMENTARY DATA

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)

Supplementary Table 1. Summary of cohort studies of total dietary fibre and stroke in the literature.

Prevalence of Incidence rate Men Women per 1000 person- Total dietary Study population diabetes HR (95% CI) Total dietary fibre* HR (95% CI) years fibre* Ascherio et al. 199814 0% 1.01 12.4 Ref – – 0.85 (0.61– 43738 men 328 strokes 16.6 – – 1.19) 323394 person- 0.85 (0.61– USA 19.7 – – years 1.19) 0.65 (0.45– 23 – – 0.93) 0.70 (0.48– 28.9 – – 1.00) Oh et al. 200515 0% 0.72 – – 10 Ref 0.97 (0.79– 78779 women 1020 strokes – – 12.8 1.19) 1418022 person- 0.89 (0.71– USA – – 14.9 years 1.10) 0.86 (0.69– – – 17.1 1.07) 0.83 (0.66– – – 21 1.04) Larsson et al. 200916 4.9 to 7.6% 9.34 16.1 Ref – – 1.01 (0.82– 26556 male smokers 3365 strokes 20.9 – – 1.25) 360187 person- 1.05 (0.87– Finland 24.7 – – years 1.25) 0.96 (0.84– 28.9 – – 1.09) 1.00 (0.86– 35.8 – – 1.17) Eshak et al. 201017 3 to 7% 1.32 <7.8 Ref <8.5 Ref 23119 men and 35611 1.14 (0.74– 0.78 (0.55– 983 strokes 7.8–9.4 8.5–9.9 women 1.76) 1.12) 743167 person- 1.12 (0.74– 1.08 (0.76– Japan 9.5–10.8 10.0–11.1 years 1.69) 1.54) 1.15 (0.70– 0.89 (0.61– 10.9–12.6 11.2–12.7 1.56) 1.30) >12.6 1.09 (0.75– >12.7 1.05 (0.73–

1.58) 1.51) Kokubo et al. 201118 2 to 9% 2.84 6 Ref 7.8 Ref 40046 men and 46341 0.94 (0.78– 0.89 (0.71– 2553 strokes 9.8 11.8 women 1.14) 1.11) 899141 person- 0.89 (0.71– 0.85 (0.67– Japan 11.7 13.7 years 1.11) 1.08) 0.92 (0.73– 0.73 (0.55– 14 15.9 1.17) 0.95) 1.00 (0.76– 0.64 (0.46– 19.9 21.6 1.32) 0.88) Wallstrom et al. 201219 0% 2.71 5.8 Ref 6.5 Ref 8139 men and 12535 755 ischaemic 0.87 (0.64– 0.70 (0.50– 7.1 8.1 women strokes 1.17) 0.98) 279099 person- 0.86 (0.63– 0.88 (0.64– Sweden 8.2 9.3 years 1.16) 1.21) 0.86 (0.63– 0.77 (0.55– 9.3 10.6 1.17) 1.08) 0.69 (0.49– 0.73 (0.52– 11.4 12.9 0.96) 1.04) HR: hazard ratio, CI: confidence interval *Means in quintiles for Kokubo et al., medians in quintiles for others

Supplementary Table 2. Cox regression analysis of incidence of cerebral infarction* and intake of total, soluble and insoluble dietary fibre and vegetables and fruits.

Quartile analysis Linear analysis

Q2 Q3 Q4 HR per

Q1 HR 95%CI p HR 95%CI p HR 95%CI p 1g increase 95%CI p

Total dietary fibre, mean±SD 8.7±1.6 12.5±0.9 15.8±1.0 21.8±4.0

Age and sex adjusted Ref 0.56 (0.27–1.17) 0.12 0.56 (0.27–1.19) 0.13 0.63 (0.31–1.28) 0.21 0.95 (0.90–1.00) 0.07

Adjusted for risk factors† Ref 0.41 (0.17–0.96) 0.04 0.45 (0.18–1.12) 0.08 0.46 (0.14–1.53) 0.20 0.85 (0.76–0.95) 0.01

Further adjusted for energy‡ Ref 0.41 (0.17–0.98) 0.05 0.45 (0.17–1.17) 0.10 0.46 (0.12–1.68) 0.24 0.83 (0.73–0.94) <0.01

Soluble dietary fibre, mean±SD 2.1±0.4 2.9±0.2 3.7±0.3 5.1±1.2

Age and sex adjusted Ref 0.61 (0.30–1.23) 0.16 0.53 (0.24–1.14) 0.11 0.53 (0.26–1.08) 0.08 0.79 (0.62–1.00) 0.05

Adjusted for risk factors* Ref 0.48 (0.21–1.09) 0.08 0.39 (0.15–1.00) 0.05 0.37 (0.11–1.21) 0.10 0.54 (0.33–0.88) 0.01

Further adjusted for energy† Ref 0.47 (0.20–1.09) 0.08 0.38 (0.14–1.03) 0.06 0.36 (0.10–1.28) 0.11 0.49 (0.28–0.85) 0.01

Insoluble dietary fibre, mean±SD 6.3±1.2 9.0±0.7 11.4±0.9 15.8±2.9

Age and sex adjusted Ref 0.62 (0.30–1.28) 0.20 0.58 (0.27–1.23) 0.15 0.67 (0.33–1.37) 0.27 0.94 (0.87–1.01) 0.08

Adjusted for risk factors† Ref 0.54 (0.24–1.23) 0.14 0.42 (0.16–1.08) 0.07 0.50 (0.15–1.66) 0.26 0.82 (0.70–0.96) 0.01

Further adjusted for energy‡ Ref 0.54 (0.24–1.26) 0.15 0.42 (0.16–1.13) 0.09 0.51 (0.14–1.83) 0.30 0.80 (0.67–0.95) 0.01

Vegetables and fruits, mean±SD 228.7±84.0 371.9±83.0 499.0±93.8 721.4±197.3

Age and sex adjusted Ref 1.07 (0.54–2.10) 0.85 0.69 (0.32–1.51) 0.35 0.57 (0.25–1.27) 0.17 0.999 (0.997–1.000) 0.04

Adjusted for risk factors† Ref 0.96 (0.45–2.06) 0.91 0.59 (0.23–1.49) 0.27 0.40 (0.13–1.22) 0.11 0.997 (0.995–0.999) 0.01

Further adjusted for energy‡ Ref 0.97 (0.45–2.08) 0.93 0.60 (0.24–1.52) 0.28 0.41 (0.13–1.26) 0.12 0.997 (0.995–0.999) 0.01

HR: hazard ratio, CI: confidence interval

*Cerebral infarction is according to guidelines defined by the Ministry of Health, Labor, and Welfare of Japan and WHO criteria. The numbers of incident cerebral infarction were 19, 12, 11, and 15 in total dietary fibre quartiles, 19, 14, 10, and 14 in soluble dietary fibre quartiles, 18, 13, 11, and 15 in insoluble dietary fibre quartiles, and 16, 19, 11, and 11 in vegetables and fruits quartiles, respectively. †Adjusted for age, sex, body mass index, HbA1C, diabetes duration, diabetic retinopathy, treatment by insulin, treatment by oral hypoglycaemic agents, systolic blood pressure, LDL cholesterol, HDL cholesterol, triglycerides, current smoker, physical activity, alcohol intake, proportions of total fat, saturated fatty acids, n-6 fatty acids and n-3 fatty acids, dietary cholesterol and sodium intake ‡Further adjusted for total energy intake