1. Journal Club 埼玉医科大学 総合医療センター 内分泌・糖尿病内科 Department of Endocrinology and Diabetes, Saitama Medical Center, Saitama Medical University 松田 昌文 Matsuda, Masafumi 2014 年 1 月 16 日 8:30-8:55 ８階 医局 Yates T1, Haffner SM2, Schulte PJ3, Thomas L3, Huffman KM3, Bales CW4, Califf RM3, Holman RR5, McMurray JJ6, Bethel MA5, Tuomilehto J7, Davies MJ8, Kraus WE3. Association between change in daily ambulatory activity and cardiovascular events in people with impaired glucose tolerance (NAVIGATOR trial): a cohort analysis. Lancet. 2013 Dec 19. pii: S0140-6736(13)62061-9. doi: 10.1016/S0140- 6736(13)62061-9.

2. NAVIGATOR 試験デザイン Nateglinide And Valsartan in Impaired Glucose Tolerance Outcome Research 試験デザイン： 2 x 2 比較試験（二重盲検比較試験） 用量：ディオバン１６０ mg ナテグリニド６０ mg * 全例に生活習慣改善プログラムが取り組まれる Valsartan/Nateglinide (n=2316) Nateglinide/Placebo (n=2329) Valsartan/Placebo (n=2315) Placebo/Placebo (n=2346) ナテグリニド比較 バルサルタン比較 最終登録例数は 9,306 例 N Engl J Med. 2010 Apr 22;362(16):1477-90. N Engl J Med. 2010 Apr 22;362(16):1463-76.

3. 結果 1 次エンドポイント （ディオバン群） | Presentation Title | Presenter Name | Date | Subject | Business Use Only3 ①糖尿病新規発症抑制 DIO 群で 1,532 例（ 33.1 ％）プラセボ群で 1,722 例（ 36.8 ％） 相対的新規発症リスクを 14 ％有意に低下（ P<0.001 ） ②複合ＣＶイベント DIO 群で 672 例（ 14.5 ％）プラセボ群で 693 例（ 14.8 ％） 両群同等であり、有意差は認められなかった ③複合コアＣＶイベント DIO 群で 375 例（ 8.1 ％）プラセボ群で 377 例（ 8.1 ％） 両群同等であり、有意差は認められなかった

4. 参考： 1 次エンドポイント （ナテグリニド群） | Presentation Title | Presenter Name | Date | Subject | Business Use Only4 ナテグリニド群においては、 糖尿病新規発症抑制、心血管イベント発症抑制 いずれも有意差がありませんでした。 ①糖尿病新規発症抑制 ナテグリニド群で 1,674 例（ 36.0 ％）プラセボ群で 1,580 例（ 33.9 ％） (Hazard Ratio 1.07, 95%CI 1.00-1.15; P=0.05) ②複合ＣＶイベント ナテグリニド群で 658 例（ 14.2 ％）プラセボ群で 707 例（ 15.2 ％） （ Hazard Ratio 0.93 95%CI 0.83-1.01;P=0.16) ③複合コアＣＶイベント ナテグリニド群で 365 例（ 7.9 ％）プラセボ群で 387 例（ 8.3 ％） （ Hazard Ratio 0.94 95%CI, 0.82-1.09; P=0.43)

5. Dr Thomas Yates, PhDa, b, Corresponding author contact information, E-mail the corresponding author, Steven M Haffner, MDc, Phillip J Schulte, PhDd, Laine Thomas, PhDd, Kim M Huffman, MDd, Connie W Bales, PhDd, e, Robert M Califf, MDd, Rury R Holman, MDf, John J V McMurray, MDg, M Angelyn Bethel, MDf, Jaakko Tuomilehto, MDh, i, j, Melanie J Davies, MDa, b, William E Kraus, MDd a NIHR Leicester-Loughborough Diet, Lifestyle, and Physical Activity Biomedical Research Unit, Leicester, UK b Leicester Diabetes Centre, College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK c Shavano Park, USA d Duke Clinical Research Institute, Duke University School of Medicine, Durham, NC, USA e Durham VA Medical Center, Durham, NC, USA f Diabetes Trials Unit, University of Oxford, Oxford, UK g British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow, UK h Centre for Vascular Prevention, Danube University Krems, Krems, Austria i South Ostrobothnia Central Hospital, Seinajoki, Finland j King Abdulaziz University, Jeddah, Saudi Arabia Published online December 20, 2013 http://dx.doi.org/10.1016/S0140-6736(13)62061-9

6. Background The extent to which change in physical activity can modify the risk of cardiovascular disease in individuals at high cardiovascular risk is uncertain. We investigated whether baseline and change in objectively- assessed ambulatory activity is associated with the risk of a cardiovascular event in individuals at high cardiovascular risk with impaired glucose tolerance.

7. Methods We assessed prospective data from the NAVIGATOR trial involving 9306 individuals with impaired glucose tolerance who were recruited in 40 countries between January, 2002, and January, 2004. Participants also either had existing cardiovascular disease (if age ≥50 years) or at least one additional cardiovascular risk factor (if age ≥55 years). Participants were followed-up for cardiovascular events (defined as cardiovascular mortality, non-fatal stroke, or myocardial infarction) for 6 years on average and had ambulatory activity assessed by pedometer at baseline and 12 months. Adjusted Cox proportional hazard models quantified the association of baseline and change in ambulatory activity (from baseline to 12 months) with the risk of a subsequent cardiovascular event, after adjustment for each other and potential confounding variables. This study is registered with ClinicalTrials.govNCT00097786.

13. Findings During 45 211 person-years follow-up, 531 cardiovascular events occurred. Baseline ambulatory activity (hazard ratio [HR] per 2000 steps per day 0·90, 95% CI 0·84–0·96) and change in ambulatory activity (0·92, 0·86–0·99) were inversely associated with the risk of a cardiovascular event. Results for change in ambulatory activity were unaffected when also adjusted for changes in body-mass index and other potential confounding variables at 12 months.

14. Interpretation In individuals at high cardiovascular risk with impaired glucose tolerance, both baseline levels of daily ambulatory activity and change in ambulatory activity display a graded inverse association with the subsequent risk of a cardiovascular event. Funding Novartis Pharmaceuticals.

15. Message NAVIGATOR 試験に参加した心血管リスクの高い耐糖 能異常患者 9306 人のデータを基に、日々の歩行運動と 心血管イベントとの関連をコホート解析で検証。ベース ライン時の歩行計歩数および 12 カ月時の歩数変化値は 心血管イベントリスクとの逆相関を示した （ 2000steps /day の調整後ハザード比 0.90 、 0.92 ）。