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 2012 年 1 月 5 日 8:30-8:55 ８階 医局 Nerenberg KA, Goyal A, Xavier D, Sigamani A, Ng J, Mehta SR, Díaz R, Kosiborod M, Yusuf S, Gerstein HC; for the RECREATE Investigators. Piloting a Novel Algorithm for Glucose Control in the Coronary Care Unit: The RECREATE (REsearching Coronary REduction by Appropriately Targeting Euglycemia) trial. Diabetes Care. 2012 Jan;35(1):19-24. Epub 2011 Nov 10.

2. 病棟血糖管理マニュアル 理論と実践 ( 第 1 版増補 ) 本書は血糖管理の理論を詳説し、臨床症例を通 じて理論をいかに実践に結びつけるかを述べた マニュアルで、好評の第 1 版（ 2008 年刊行）の 増補版。診断基準の改訂、 CSII や持効型インス リンの普及など、糖尿病診療情勢の変化に対応。 さらに、マニュアルの利便性の向上を図り、研 修医・看護師など医療スタッフの理解促進のた め「血糖管理のポイント」、および実際の運用 例として「簡易血糖管理マニュアル」を追加。 インスリン治療については：

3. Surgical ICU でのインスリン強化療法による 死亡率減少

4. N Engl J Med 2001;345:1359-67. CONVENTIONAL TREATMENT (N=783) INTENSIVE TREATMENT (N=765) Male sex — (%) 557 (71) vs 544 (71) Age — yr 62.2±13.9 vs 63.4±13.6

5. 重症入院患者へのインスリン治療：死亡 率 （無作為ランダム化研究のメタ解析） 35 publications, n=8478 Ref.15 of the current article

6. The NICE-SUGAR Study Investigators. N Engl J Med 2009;360:1283-1297

7. Diabetes Care 35:19–24, 2012 the 1 Population Health Research Institute McMaster University, Hamilton, Ontario, Canada; the 2 Department of Medicine, Emory University, Atlanta, Georgia; the 3 Department of Pharmacology, St. John’s Medical School, Bangalore, India; the 4 Department of Pharmacology, St. John’s Research Institute, Bangalore, India; the 5 Department of Medicine, McMaster University, Hamilton, Ontario, Canada; the 6 Etudios Cardiologica Latin America, Rosario, Argentina; the 7 Mid-America Heart and Vascular Institute of Saint Luke’s Hospital and the Department of Medicine, University of Missouri, Kansas City, Missouri; and the 8 Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, Canada.

8. OBJECTIVE Elevated glucose levels are common after an acute myocardial infarction (AMI) and increase the risk of death. Prior trials of glucose control after AMI have been inconsistent in their ability to lower glucose levels and have reported mixed effects on mortality. We developed a paper-based glucose-lowering algorithm and assessed its feasibility and safety in the setting of AMI.

9. RESEARCH DESIGN AND METHODS A total of 287 participants with an acute ST segment elevation myocardial infarction (STEMI) and a capillary glucose level ≧ 8.0 mmol/L were randomly allocated to glucose management with intravenous glulisine insulin using this algorithmin the coronary care unit (CCU), followed by once-daily subcutaneous insulin glargine for 30 days versus standard glycemic approaches. The primary outcome was a difference in mean glucose levels at 24 h. Participants were followed for clinical outcomes through 90 days.

10. Figure 1 RECREATE trial flow diagram.

11. Table 1 Baseline patient characteristics and AMI management

12. 182mg/dl 176mg/dl 1.14mg/dl

14. The Killip classification is a system used in individuals with an acute myocardial infarction (heart attack), in order to risk stratify them. Individuals with a low Killip class are less likely to die within the first 30 days after their myocardial infarction than individuals with a high Killip class. Killip class I includes individuals with no clinical signs of heart failure. Killip class II includes individuals with rales or crackles in the lungs, an S3, and elevated jugular venous pressure. Killip class III describes individuals with frank acute pulmonary edema. Killip class IV describes individuals in cardiogenic shock or hypotension (measured as systolic blood pressure lower than 90 mmHg), and evidence of peripheral vasoconstriction (oliguria, cyanosis or sweating).

15. Yale 大学プロトコール／若干の修正 Diabetes Care 27:461, 2004 を改変

16. 6.5117 7.0126 8.3149 8.9160 10.8194 12.5225 14.7265 mM mg/dl しろうと！

17. 3.94.96.58.811.016.5 7088117158198297 mM mg/dl 4.97.29.412.2 88130169220

20. Diabetes Mellitus Insulin Glucose Infusion in Acute Myocardial Infarction (DIGAMI): Benefit of Tight Glycemic Control in No Insulin – Low Risk Cohort Malmberg K, et al. BMJ. 1997;314:1512-1515. 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0 Mortality Total CohortNo Insulin – Low Risk Years in Study Control Insulin-glucose Infusion 012345012345 Control p =.0111p =.004 n=133 n=139 n=314 n=306

21. Glucose Control Summary (All subjects Kameda Medical Center 2006-2008) Partly presented at the 44 th EASD, Sep. 8-11, 2008, Rome, Italy, Diabetologia 51(Supplement 1): S440, 2008

22. RESULTS At 24 h, the mean glucose level was 1.41mmol/L (95%CI 0.69–2.13) lower in the insulin (6.53 vs. 7.94mmol/L). Differences in glucose levels were maintained at 72 h and 30 days. A total of 22.7% of the insulin group versus 4.4% of the standard group had biochemical hypoglycemia (with neither signs nor symptoms) in the CCU because of lower glycemic goals. However, there were no differences in symptomatic hypoglycemia or clinical outcomes between the groups.

23. CONCLUSIONS A paper-based insulin algorithm targeting glucose levels of 5.0–6.5 mmol/L (90–117 mg/dL) can be feasibly implemented in the CCU. A cardiovascular outcomes trial using this approach can determine whether targeted glucose lowering improves patient outcomes.

24. Message/Comments まぁ Novel と言っているが、基本的には Yale 大学プロ トコールを簡略化した感じ。 一定の方法で慣れてくるとだいたいあまり低血糖は普 通起さないとは感じるが、 23% は多すぎ！ 差はまぁともかく？？？ 例）もし -15% 死亡が異なるとすると 心筋梗塞で 9% しか死なないと仮定すると、 １００人心筋梗塞で血糖管理で９人死ぬか８人死ぬか の１人の差にしかならない！ でも、 90% 死ぬとすると 90 人死ぬか 76 人死ぬか 14 人 の差になる。