Transcript PowerPoint - 埼玉医科大学総合医療センター 内分泌・糖尿病内科

Journal Club
Jordi Salas-Salvadó, MD, PhD*; Mònica Bulló, PhD; Ramón Estruch, MD, PhD; Emilio Ros,
MD, PhD; Maria-Isabel Covas, DPharm; Núria Ibarrola-Jurado, RD, PhD; Dolores Corella,
DPharm, PhD; Fernando Arós, MD, PhD; Enrique Gómez-Gracia, MD, PhD; Valentina RuizGutiérrez, PhD; Dora Romaguera, MD, PhD; José Lapetra, MD, PhD; Rosa Maria LamuelaRaventós, DPharm, PhD; Lluís Serra-Majem, MD, PhD; Xavier Pintó, MD, PhD; Josep Basora,
MD, PhD; Miguel Angel Muñoz, MD, PhD; José V. Sorlí, MD, PhD; and Miguel A. MartínezGonzález, MD, PhD*
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; CHiP 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/NEJMoa1302564.
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 Med 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, 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: ISRCTN35739639)
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;
MedDiet Mediterranean diet.
EVOO (50 mL/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; MedDiet =
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/m2 and obesity as
BMI >=30 kg/m2.
§ 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/dL), HDL cholesterol
levels <=1.03 mmol/L
(=<39.77 mg/dL) in men
or =<1.29 mmol/L
(=<49.81 mg/dL) 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.
Message
心血管リスクが高い男女3541人（55-80歳）を対
象に、地中海食の糖尿病一次予防効果を多施設共
同無作為化試験のサブグループ解析で検討。中央
値4.1年の追跡で、対照群（低脂肪食の助言）に
対する2型糖尿病発症の多変量調整後ハザード比
は、地中海食にオリーブオイルを追加した群で
0.60、ナッツ類を追加した群で0.82だった。
やっぱりオリーブオイルは良い！?
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/NEJMoa1302564
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). CHiP
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 75th and 25th
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; CHiP Current Controlled Trials number,
ISRCTN61735247.)
There was also a remarkable difference that emerged over the course of the 1year 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 CHiP 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 (ClinicalTrials.gov number,
NCT01565941) are accrued.
Message
ICUで人工換気と血管作動薬を必要とする小児患者
1369人を対象に、厳格な血糖制御（目標値72126mg/dL）の有用性を無作為化試験で標準制御と比
較（CHiP試験）。主要評価項目の30日生存時の人工
換気不使用日数の群間差は0.36日だった。重症小児
の厳格な血糖制御は、主要な臨床転帰に大きく影響
しないと示唆された。
コストが有意に厳格な血糖管理群がよい点は抄録の
結論には入れていないが???
大人と逆で心血管の手術では血糖管理はしない方が
よさそう！