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Journal Club Jordi Salas-Salvadó, MD, Ph. D*; Mònica Bulló, Ph. D; Ramón Estruch, MD, Ph. D; Emilio Ros, MD, Ph. D; Maria-Isabel Covas, DPharm; Núria Ibarrola-Jurado, RD, Ph. D; Dolores Corella, DPharm, Ph. D; Fernando Arós, MD, Ph. D; Enrique Gómez-Gracia, MD, Ph. D; Valentina Ruiz-Gutiérrez, Ph. D; Dora Romaguera, MD, Ph. D; José Lapetra, MD, Ph. D; Rosa Maria Lamuela-Raventós, DPharm, Ph. D; Lluís Serra-Majem, MD, Ph. D; Xavier Pintó, MD, Ph. D; Josep Basora, MD, Ph. D; Miguel Angel Muñoz, MD, Ph. D; José V. Sorlí, MD, Ph. D; and Miguel A. Martínez-González, MD, Ph. D* Prevention of Diabetes With Mediterranean Diets: A Subgroup Analysis of a Randomized Trial Ann Intern Med. 2014; 160(1): 1 -10 -10. Macrae D, Grieve R, Allen E, Sadique Z, Morris K, Pappachan J, Parslow R, Tasker RC, Elbourne D; CHi. P Investigators. A randomized trial of hyperglycemic control in pediatric intensive care. N Engl J Med. 2014 Jan 9; 370(2): 107 -18. doi: 10. 1056/NEJMoa 1302564. 2014年 1月23日 8: 30 -8: 55 ８階 医局 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
Original Article Weight Loss with a Low-Carbohydrate, Mediterranean, or Low-Fat Diet Israel, Germany, Boston Iris Shai, R. D. , Ph. D. , Dan Schwarzfuchs, M. D. , Yaakov Henkin, M. D. , Danit R. Shahar, R. D. , Ph. D. , Shula Witkow, R. D. , M. P. H. , Ilana Greenberg, R. D. , M. P. H. , Rachel Golan, R. D. , M. P. H. , Drora Fraser, Ph. D. , Arkady Bolotin, Ph. D. , Hilel Vardi, M. Sc. , Osnat Tangi-Rozental, B. A. , Rachel Zuk-Ramot, R. N. , Benjamin Sarusi, M. Sc. , Dov Brickner, M. D. , Ziva Schwartz, M. D. , Einat Sheiner, M. D. , Rachel Marko, M. Sc. , Esther Katorza, M. Sc. , Joachim Thiery, M. D. , Georg Martin Fiedler, M. D. , Matthias Blüher, M. D. , Michael Stumvoll, M. D. , Meir J. Stampfer, M. D. , Dr. P. H. , for the Dietary Intervention Randomized Controlled Trial (DIRECT) Group In this 2 -year trial, we randomly assigned 322 moderately obese subjects (mean age, 52 years; mean body-mass index [the weight in kilograms divided by the square of the height in meters], 31; male sex, 86%) to one of three diets: low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate, non– restricted-calorie. Shai I et al. N Engl J Med 2008; 359: 229 -241
Weight Changes during 2 Years According to Diet Group Shai I et al. N Engl J Med 2008; 359: 229 -241
Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición (R. E. , E. R. , J. S. -S. , M. -I. C. , D. C. , M. F. , J. L. , R. M. L. -R. , J. B. , J. V. S. , J. A. M. ) and the PREDIMED (Prevención con Dieta Mediterránea) Network (RD 06/0045) (R. E. , J. S. -S. , F. A. , E. G. -G. , V. R. -G. , R. M. L. -R. , L. S. -M. , X. P. , J. B. , J. V. S. , J. A. M. , M. A. M. -G. ), Instituto de Salud Carlos III, Madrid; the Department of Internal Medicine (R. E. ) and Lipid Clinic, Department of Endocrinology and Nutrition (E. R. ), Institut d’Investigacions Biomèdiques August Pi I Sunyer, Hospital Clinic, University of Barcelona, Barcelona; Human Nutrition Department, Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, Universitat Rovira i Virgili, Reus (J. S. -S. ); Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Barcelona (M. -I. C. ); the Department of Preventive Medicine, University of Valencia, Valencia (D. C. ); the Department of Cardiology, University Hospital of Alava, Vitoria (F. A. ); the Department of Preventive Medicine, University of Malaga, Malaga (E. G. -G. ); Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, Seville (V. R. -G. ); Institute of Health Sciences (IUNICS), University of Balearic Islands, and Hospital Son Espases, Palma de Mallorca (M. F. ); the Department of Family Medicine, Primary Care Division of Seville, San Pablo Health Center, Seville (J. L. ); the Department of Nutrition and Food Science, School of Pharmacy, Xarxa de Referència en Tecnologia dels Aliments, Instituto de Investigación en Nutrición y Seguridad Alimentaria, University of Barcelona, Barcelona (R. M. L. -R. ); the Department of Clinical Sciences, University of Las Palmas de Gran Canaria, Las Palmas (L. S. -M. ); Lipids and Vascular Risk Unit, Internal Medicine, Hospital Universitario de Bellvitge, Hospitalet de Llobregat, Barcelona (X. P. ); Primary Care Division, Catalan Institute of Health, Institut d’Investigació en Atenció Primària Jordi Gol, Tarragona-Reus (J. B. ) and Barcelona (M. A. M. ); Primary Care Division, Valencia Institute of Health, Valencia (J. V. S. ); and the Departments of Nutrition and Food Sciences, Physiology and Toxicology (J. A. M. ) and Preventive Medicine and Public Health (M. A. M. -G. ), University of Navarra, Pamplona — all in Spain. N Engl J Med. 2013; 368: 1279 -90.
Figure 1. Kaplan–Meier Estimates of the Incidence of Outcome Events in the Total Study Population. Panel A shows the incidence of the primary end point (a composite of acute myocardial infarction, stroke, and death from cardiovascular causes). CI denotes confidence interval, EVOO extra-virgin olive oil, and Mediterranean. N Engl J Med. 2013; 368: 1279 -90.
Diabetes Care 34: 14– 19, 2011
The Instituto de Salud Carlos III (Institute of Health Carlos III, ISCIII) is the main Public Research Entity funding, managing and carrying out biomedical research in Spain. 保健研究所「 カルロス 3世」（ISCIII） スペインの公的機関である 科学イノベーション省 (旧厚生 労働省)付属施設 Salud: 健康、乾杯
The Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y Nutrición, and PREDIMED Network, Instituto de Salud Carlos III, Madrid, Spain; Hospital Universitari Sant Joan, Institut d’Investigació Sanitaria Pere Virgili, and Universitat Rovira i Virgili, Reus, Spain; Institut d’Investigacions Biomèdiques August Pi i Sunyer, Hospital Clinic, School of Pharmacy, Xarxa de Referència en Tecnologia dels Aliments, and Instituto de Investigación en Nutrición y Seguridad Alimentaria, University of Barcelona, Cardiovascular and Nutrition Research Group, Institut de Recerca Hospital del Mar, Hospital Universitario de Bellvitge, and Hospitalet de Llobregat, Barcelona, Spain; University of Valencia and Valencia Institute of Health, Valencia, Spain; University Hospital of Alava, Vitoria, Spain; University of Malaga, Spain; Instituto de la Grasa, Consejo Superior de Investigaciones Cientificas, and San Pablo Health Center, Seville, Spain; Research Unit, University Hospital Son Espases, Balearic Islands, Spain; School of Public Health, Imperial College London, United Kingdom; University of Las Palmas de Gran Canaria, Las Palmas, Spain; University of Navarra, Pamplona, Spain; and Catalan Institute of Health, Institut d’Investigació en Atenció Primària Jordi Gol, Tarragona-Reus and Barcelona, Spain. Ann Intern Med. 2014; 160: 1 -10.
Background: Interventions promoting weight loss can reduce the incidence of type 2 diabetes mellitus. Whether dietary changes without calorie restriction also protect from diabetes has not been evaluated. Objective: To assess the efficacy of Mediterranean diets for the primary prevention of diabetes in the Prevención con Dieta Mediterránea trial, from October 2003 to December 2010 (median follow-up, 4. 1 years).
Design: Subgroup analysis of a multicenter, randomized trial. (Current Controlled Trials: ISRCTN 35739639) Setting: Primary care centers in Spain. Participants: Men and women without diabetes (3541 patients aged 55 to 80 years) at high cardiovascular risk. Intervention: Participants were randomly assigned and stratified by site, sex, and age but not diabetes status to receive 1 of 3 diets: Mediterranean diet supplemented with extra-virgin olive oil (EVOO), Mediterranean diet supplemented with nuts, or a control diet (advice on a low-fat diet). No intervention to increase physical activity or lose weight was included. Measurements: Incidence of new-onset type 2 diabetes mellitus (prespecified secondary outcome).
Figure 1. Study flow diagram. EVOO extra-virgin olive oil; Med. Diet Mediterranean diet. EVOO (50 m. L/d) mixed nuts (30 g/d: 15 g of walnuts, 7. 5 g of almonds, and 7. 5 g of hazelnuts) at no cost.
BMI = body mass index; EVOO = extra-virgin olive oil; HDL = highdensity lipoprotein; LDL = low-density lipoprotein; Med. Diet = Mediterranean diet; MET = metabolic equivalent. * Values are numbers (percentages) unless otherwise indicated. Characteristics are for all participants without diabetes (n = 3541). † Current smoker was defined as >1 cigarette, cigar, or pipe per day. Former smoker was defined as no smoking for >=1 y. ‡ Overweight was defined as BMI >=25 kg/m 2 and obesity as BMI >=30 kg/m 2. § Systolic blood pressure >=140 mm Hg, diastolic blood pressure 90 mm Hg, or use of antihypertensive agents. LDL cholesterol levels >4. 14 mmol/L (>158. 30 mg/d. L), HDL cholesterol levels <=1. 03 mmol/L (=<39. 77 mg/d. L) in men or =<1. 29 mmol/L (=<49. 81 mg/d. L) in women, or use of lipidlowering therapy.
Figure 2. Cumulative incidence of diabetes (or either diabetes or death).
Figure 2. Cumulative incidence of diabetes (or either diabetes or death).
Results: During follow-up, 80, 92, and 101 new-onset cases of diabetes occurred in the Mediterranean diet supplemented with EVOO, Mediterranean diet supplemented with mixed nuts, and control diet groups, respectively, corresponding to rates of 16. 0, 18. 7, and 23. 6 cases per 1000 person-years. Multivariateadjusted hazard ratios were 0. 60 (95% CI, 0. 43 to 0. 85) for the Mediterranean diet supplemented with EVOO and 0. 82 (CI, 0. 61 to 1. 10) for the Mediterranean diet supplemented with nuts compared with the control diet.
Limitations: Randomization was not stratified by diabetes status. Withdrawals were greater in the control group. Conclusion: A Mediterranean diet enriched with EVOO but without energy restrictions reduced diabetes risk among persons with high cardiovascular risk. Primary Funding Source: Instituto de Salud Carlos III.
Lancet 2009; 373: 547– 56 Kaplan-Meier analysis depicting cumulative incidence of PICU death (%) for time (days) in PICU in the conventional and intensive insulin groups. The p value was obtained by log-rank testing. Am J Respir Crit Care Med 182: 351– 359, 2010 Eleven percent of the patients died in the control group, and 4% of patients in the intensive insulin group died (P = 0. 14). 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).
Royal Brompton and Harefield NHS Foundation Trust (D. M. ) and the Departments of Health Services Research and Policy (R. G. , Z. S. ) and Medical Statistics (E. A. , D. E. ) and the Clinical Trials Unit (E. A. , D. E. ), London School of Hygiene and Tropical Medicine, London, Birmingham Children's Hospital, Birmingham (K. M. ), University Hospital Southampton NHS Foundation Trust, Southampton (J. P. ), and the Division of Epidemiology, Leeds Institute of Genetics and Therapeutics, Faculty of Medicine and Health, University of Leeds, Leeds (R. P. ) — all in the United Kingdom; and the Departments of Neurology and Anesthesia, Boston Children's Hospital and Harvard Medical School, Boston (R. C. T. ). N Engl J Med 2014; 370: 107 -118 January 9, 2014 DOI: 10. 1056/NEJMoa 1302564
Background Whether an insulin infusion should be used for tight control of hyperglycemia in critically ill children remains unclear.
Methods We randomly assigned children (≤ 16 years of age) who were admitted to the pediatric intensive care unit (ICU) and were expected to require mechanical ventilation and vasoactive drugs for at least 12 hours to either tight glycemic control, with a target blood glucose range of 72 to 126 mg per deciliter (4. 0 to 7. 0 mmol per liter), or conventional glycemic control, with a target level below 216 mg per deciliter (12. 0 mmol per liter). The primary outcome was the number of days alive and free from mechanical ventilation at 30 days after randomization. The main prespecified subgroup analysis compared children who had undergone cardiac surgery with those who had not. We also assessed costs of hospital and community health services.
Figure 1. Screening, Randomization, Assessment, and Follow-up. Patients could have more than one reason for ineligibility for the study. Information on vital status up to 12 months was available for all patients, with the exception of 17 non-U. K. nationals, from the U. K. Office of National Statistics. Owing to funding constraints, the 12 -month follow-up assessment was performed only for patients who underwent randomization up to October 30, 2010 (i. e. , the followup was administratively censored). CHi. P denotes Control of Hyperglycaemia in Paediatric Intensive Care, CICU cardiac intensive care unit, and PICU pediatric intensive care unit.
Figure 2. Blood Glucose Level and Caloric Intake, According to Treatment Group. Panel A shows the mean blood glucose levels for the first 10 days after randomization, with vertical bars indicating 95% confidence intervals. To convert the values for glucose to millimoles per liter, multiply by 0. 05551. Day 1 data are the average levels from the time of randomization to the end of the day of randomization. The target range of blood glucose levels with tight glycemic control was 72 to 126 mg per deciliter. The target blood glucose level with conventional glycemic control was less than 216 mg per deciliter. The daily intake of calories intravenously and enterally is shown in Panels B and C, respectively. The horizontal lines within the boxes indicate medians, the upper and lower ends of the boxes indicate the 75 th and 25 th percentiles, respectively, and the whiskers indicate the ranges.
Results A total of 1369 patients at 13 centers in England underwent randomization: 694 to tight glycemic control and 675 to conventional glycemic control; 60% had undergone cardiac surgery. The mean between-group difference in the number of days alive and free from mechanical ventilation at 30 days was 0. 36 days (95% confidence interval [CI], − 0. 42 to 1. 14); the effects did not differ according to subgroup. Severe hypoglycemia (blood glucose, <36 mg per deciliter [2. 0 mmol per liter]) occurred in a higher proportion of children in the tight-glycemic-control group than in the conventional-glycemic-control group (7. 3% vs. 1. 5%, P<0. 001). Overall, the mean 12 -month costs were lower in the tight-glycemic-control group than in the conventional-glycemic-control group. The mean 12 -month costs were similar in the two groups in the cardiac-surgery subgroup, but in the subgroup that had not undergone cardiac surgery, the mean cost was significantly lower in the tight-glycemic-control group than in the conventional-glycemic-control group: −$13, 120 (95% CI, −$24, 682 to −$1, 559).
Conclusions This multicenter, randomized trial showed that tight glycemic control in critically ill children had no significant effect on major clinical outcomes, although the incidence of hypoglycemia was higher with tight glucose control than with conventional glucose control. (Funded by the National Institute for Health Research, Health Technology Assessment Program, U. K. National Health Service; CHi. P Current Controlled Trials number, ISRCTN 61735247. )
There was also a remarkable difference that emerged over the course of the 1 year health care follow-up: in the subgroup of patients who had not undergone cardiac surgery, the average length of stay in the hospital up to 1 year was 13. 5 days shorter with tight glycemic control than with conventional glycemic control, and the per-patient health care costs were $13, 000 less in the tightglycemic-control group. These differences were not due to early mortality. The use of renal-replacement therapies was significantly lower in the tightglycemic-control group than in the conventional-glycemic control group, although renal function was not reported. In the CHi. P trial, the non–cardiac-surgery patients appeared to differ importantly from cardiac-surgery patients, with a higher predicted mortality, and in prior data, these patients also had a higher rate and severity of hyperglycemia. it remains impossible to determine best practice for the child who requires critical care for reasons other than cardiac surgery or burns until either a metaanalysis of several trials is performed on an individual-data level or until data from an ongoing large, multicenter trial (Clinical. Trials. gov number, NCT 01565941) are accrued.