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 9 月 20 日 8:30-8:55 ８階 医局 Carnethon MR, De Chavez PJ, Biggs ML, Lewis CE, Pankow JS, Bertoni AG, Golden SH, Liu K, Mukamal KJ, Campbell-Jenkins B, Dyer AR. Association of weight status with mortality in adults with incident diabetes. JAMA. 2012 Aug 8;308(6):581-90. Agus MS, Steil GM, Wypij D, Costello JM, Laussen PC, Langer M, Alexander JL, Scoppettuolo LA, Pigula FA, Charpie JR, Ohye RG, Gaies MG; the SPECS Study Investigators. Tight Glycemic Control versus Standard Care after Pediatric Cardiac Surgery. N Engl J Med. 2012 Sep 7. [Epub ahead of print]

2. JAMA. 2012;308(6):581-590 Department of Preventive Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois (Drs Carnethon, Liu, and Dyer and Mr De Chavez); Department of Biostatistics, University of Washington, Seattle (Dr Biggs); Department of Preventive Medicine, University of Alabama School of Medicine, Birmingham (Dr Lewis); Division of Epidemiology and Community Health, University of Minnesota, Minneapolis (Dr Pankow); Division of Epidemiology, Department of Health Studies, Wake Forest University, Winston-Salem, North Carolina (Dr Bertoni); Division of Endocrinology, Department of Medi cine and Welch Center for Prevention, Johns Hopkins University, Baltimore, Maryland (Dr Golden); Division of Internal Medicine, Department of Medicine, Harvard University and Beth Israel Deaconess Medical Center, Brookline, Massachusetts (Dr Mukamal); and Jackson Heart Study Coordinating Center, Jackson State University, Jackson, Mississippi (Dr Campbell- Jenkins).

3. Context Type 2 diabetes in normal- weight adults (body mass index [BMI] < 25) is a representation of the metabolically obese normal- weight phenotype with unknown mortality consequences.

4. Objective To test the association of weight status with mortality in adults with newonset diabetes in order to minimize the influence of diabetes duration and voluntary weight loss on mortality. Design, Setting, and Participants Pooled analysis of 5 longitudinal cohort studies: Atherosclerosis Risk in Communities study, 1990-2006; Cardiovascular Health Study, 1992-2008; Coronary Artery Risk Development in Young Adults, 1987-2011; Framingham Offspring Study, 1979-2007; and Multi-Ethnic Study of Atherosclerosis, 2002- 2011. A total of 2625 participants with incident diabetes contributed 27,125 personyears of follow-up. Included were men and women (age > 40 years) who developed incident diabetes based on fasting glucose 126 mg/dL or greater or newly initiated diabetes medication and who had concurrent measurements of BMI. Participants were classified as normal weight if their BMI was 18.5 to 24.99 or overweight/obese if BMI was 25 or greater. Main Outcome Measures Total, cardiovascular, and noncardiovascular mortality.

6. Body mass index (BMI) was calculated as weight in kilograms divided by height in meters squared. Normal weight was defined as a BMI of 18.5-24.9; those categorized as overweight/obese had a BMI of 25.

15. Results The proportion of adults who were normal weight at the time of incident diabetes ranged from 9% to 21% (overall 12%). During follow-up, 449 participants died: 178 from cardiovascular causes and 253 from noncardiovascular causes (18 were not classified). The rates of total, cardiovascular, and noncardiovascular mortality were higher in normal-weight participants (284.8, 99.8, and 198.1 per 10 000 personyears, respectively) than in overweight/obese participants (152.1, 67.8, and 87.9 per 10,000 person-years, respectively). After adjustment for demographic characteristics and blood pressure, lipid levels, waist circumference, and smoking status, hazard ratios comparing normal-weight participants with overweight/obese participants for total, cardiovascular, and noncardiovascular mortality were 2.08 (95% CI, 1.52-2.85), 1.52 (95% CI, 0.89- 2.58), and 2.32 (95% CI, 1.55-3.48), respectively.

16. Conclusion Adults who were normal weight at the time of incident diabetes had higher mortality than adults who are overweight or obese.

17. Message 糖尿病（ DM ）のコホート研究 5 件（被験者 2625 人）のプール解析から、体重と死亡 の関連を検討。糖尿病発症時に正常体重の 患者は 12 ％だった。死亡率は過体重群より 正常体重群で高かった。血圧、脂質レベル などで調整後の正常体重群と過体重群の比 較死亡ハザード比は、総死亡 2.08 、心血管 死 1.52 、非心血管死 2.32 だった。 （まぁ海外では体重が少なくて糖尿病とい うのはおかしな集団なので日本では？）

20. Background In some studies, tight glycemic control with insulin improved outcomes in adults undergoing cardiac surgery, but these benefits are unproven in critically ill children at risk for hyperinsulinemic hypoglycemia. We tested the hypothesis that tight glycemic control reduces morbidity after pediatric cardiac surgery.

21. Methods In this two-center, prospective, randomized trial, we enrolled 980 children, 0 to 36 months of age, undergoing surgery with cardiopulmonary bypass. Patients were randomly assigned to either tight glycemic control (with the use of an insulindosing algorithm targeting a blood glucose level of 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]) or standard care in the cardiac intensive care unit (ICU). Continuous glucose monitoring was used to guide the frequency of blood glucose measurement and to detect impending hypoglycemia. The primary outcome was the rate of health care–associated infections in the cardiac ICU. Secondary outcomes included mortality, length of stay, organ failure, and hypoglycemia.

22. Figure 1. Assessment, Randomization, and Follow-up of the Study Patients. CPB denotes cardiopulmonary bypass.

25. The group assigned to tight glycemic control (hereafter referred to as the glycemic-control group) received an intravenous infusion of regular human insulin at the lowest dose necessary to achieve normoglycemia (defined as a blood glucose level of 80 to 110 mg per deciliter [4.4 to 6.1 mmol per liter]). Dose adjustment was guided by frequent bedside measurements with a blood glucose meter (LifeScan SureStep Flexx in Boston and Roche ACCU-CHEK Inform in Michigan). Glucose levels were entered into a proportional–integral–derivative insulin-dosing algorithm on a Microsoft Excel spreadsheet displayed on a dedicated laptop computer at the patient’s bedside. A continuous glucose monitor (Guardian REAL-Time device, Medtronic Diabetes) was used for the duration of insulin therapy in the glycemic-control group to guide the frequency of blood glucose checks and to alert the bedside nurse to impending or actual hypoglycemia; however, no decisions regarding insulin dosing or glucose rescue were made solely on the basis of readings from continuous glucose monitors. Continuous glucose monitoring was used in the standard-care group only for the first 3 days in the cardiac ICU, to alert bedside clinicians to impending hypoglycemia. The standard-care group had no set target range for blood glucose management; patients were treated according to the preference of the attending cardiac intensivist. A blood-sampling system (VAMP Jr., Edwards Lifesciences) was used in both groups to reduce blood loss, sample dilution, and the risk of catheter contamination associated with frequent blood draws. The study protocol was discontinued on removal of the arterial catheter, at the time of discharge from the cardiac ICU, or 30 days after randomization, whichever came first.

26. Wintergerst KA, Deiss D, Buckingham B, Cantwell M, Kache S, Agarwal S, Wilson DM, Steil G. Glucose control in pediatric intensive care unit patients using an insulin-glucose algorithm. Diabetes Technol Ther. 2007 Jun;9(3):211-22.

28. Figure 2. Glucose, Insulin, and Nutrition, According to Treatment Group. Data in all the panels are for full 24-hour days during the period of critical illness. Panel A shows time- weighted blood glucose averages calculated from all blood glucose samples on the day of postoperative admission to the cardiac intensive care unit (ICU) (day 1) and the subsequent 6 days (7 a.m. to 6:59 a.m.). Panel B shows total daily insulin delivery. Panel C shows average daily glucose infusion rates. Panel D shows the daily percentage of nutrition delivered through the enteral route. Panel E shows total kilocalories of nutrition per kilogram of body weight per day. In each panel, the boxes represent the interquartile range (25th percentile to 75th percentile) and the horizontal lines the median; the whiskers extend to the 5th and 95th percentiles. To convert the values for glucose to millimoles per liter, multiply by 0.05551.

31. Results A total of 444 of the 490 children assigned to tight glycemic control (91%) received insulin versus 9 of 490 children assigned to standard care (2%). Although normoglycemia was achieved earlier with tight glycemic control than with standard care (6 hours vs. 16 hours, P<0.001) and was maintained for a greater proportion of the critical illness period (50% vs. 33%, P<0.001), tight glycemic control was not associated with a significantly decreased rate of health care–associated infections (8.6 vs. 9.9 per 1000 patient-days, P = 0.67). Secondary outcomes did not differ significantly between groups, and tight glycemic control did not benefit high-risk subgroups. Only 3% of the patients assigned to tight glycemic control had severe hypoglycemia (blood glucose <40 mg per deciliter [2.2 mmol per liter]).

32. Conclusions Tight glycemic control can be achieved with a low hypoglycemia rate after cardiac surgery in children, but it does not significantly change the infection rate, mortality, length of stay, or measures of organ failure, as compared with standard care. (Funded by the National Heart, Lung, and Blood Institute and others; SPECS ClinicalTrials.gov number, NCT00443599.)

33. Message 心臓手術を受けた生後 0-36 カ月の小児 980 人を 対象に、厳格な術後血糖管理（ 80- 110mg/dL ）と合併症の関連を前向き無作為化 試験で検討（ SPECS 試験）。血糖管理群では正 常血糖達成は標準的治療群より早く、重度低血糖 発生率は 3 ％と低かった。主要評価項目の医療関 連感染症の発生減少と厳格血糖管理に有意な関連 はなかった。 ただし CGM をどちらも用いて 血糖に差がほと んどないし．．．