Journal Club
The DCCT/EDIC Research Group
Intensive Diabetes Therapy and Glomerular Filtration Rate in Type 1
Diabetes.
N Engl J Med. 2011 Nov 12. [Epub ahead of print]
2011年11月24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
1型糖尿病
DCCT/EDIC
-42%
（P=0.02）
0.12
心
血
管
イ
ベ
ン
ト
の
累
積
発
生
率
0.10
従来療法群（N=589）
0.08
0.06
A1C 7.4% vs 9.1%
A1C 8.0% vs 8.2%
0.04
0.02
強化療法群（N=593）
0.00
0
1
2
3
4
5
No. at Risk
強化療法群
従来療法群
705
714
6
7
8
9 10 11 12 13 14 15 16 17 18 19 20 21
観察期間（年）
683
688
629
618
113
92
N Engl J Med 2005; 353: 2643-53.
Diabetic retinopathy cumulative incidence
Secondary prevention
76%
conventional
54%
Incidence
Incidence
Primary prevention
conventional
intensive
intensive
years
years
conventional
conventional
intensive
intensive
4
FIG. 2. Estimated cumulative
incidence of further 3-step
progression of retinopathy from
DCCT closeout, by DCCT
treatment group, through EDIC
year 4, for adolescents (A) and
for adults (B); through EDIC
year 10, for adolescents (C) and
for adults (D). Subjects with
prior scatter photocoagulation
during DCCT (7 adolescents and
29 adults) were excluded from
analyses. Based on Weibull
regression models adjusted for
the level of retinopathy at the
end of the DCCT, primary vs.
secondary cohort, the A1C value
on entry to the DCCT, and
diabetes duration at DCCT
baseline. Hazard reduction was
for intensive therapy compared
with conventional therapy.
Diabetes 59:1244–1253, 2010
Ian H. de Boer, M.D., University of Washington, Seattle; Wanjie Sun, M.S., Patricia A.
Cleary, M.S., and John M. Lachin, Sc.D., The George Washington University, Rockville,
MD; Mark E. Molitch, M.D., Northwestern University, Chicago; Michael W. Steffes, M.D.,
Ph.D., University of Minnesota, Minneapolis; and Bernard Zinman, M.D., Samuel
Lunenfeld Research Institute, Mount Sinai Hospital, University of Toronto, Toronto
10.1056/nejmoa1111732 nejm.org
Background
An impaired glomerular filtration rate
(GFR) leads to end-stage renal disease
and increases the risks of cardiovascular
disease and death. Persons with type 1
diabetes are at high risk for kidney
disease, but there are no interventions
that have been proved to prevent
impairment of the GFR in this population.
Methods
In the Diabetes Control and Complications Trial (DCCT), 1441
persons with type 1 diabetes were randomly assigned to 6.5
years of intensive diabetes therapy aimed at achieving nearnormal glucose concentrations or to conventional diabetes
therapy aimed at preventing hyperglycemic symptoms.
Subsequently, 1375 participants were followed in the
observational Epidemiology of Diabetes Interventions and
Complications (EDIC) study. Serum creatinine levels were
measured annually throughout the course of the two studies. The
GFR was estimated with the use of the Chronic Kidney Disease
Epidemiology Collaboration formula. We analyzed data from the
two studies to determine the long-term effects of intensive
diabetes therapy on the risk of impairment of the GFR, which
was defined as an incident estimated GFR of less than 60 ml per
minute per 1.73 m2 of body-surface area at two consecutive
study visits.
Figure 1. Cumulative Incidence of an Impaired Glomerular Filtration Rate, According to Treatment Group. An impaired glomerular
filtration rate (GFR) was defined as a sustained estimated GFR of less than 60 ml per minute per 1.73 m2 of body-surface area. The
cumulative incidence of an impaired GFR is shown according to the group to which the participants had been randomly assigned in
the Diabetes Control and Complications Trial, with death accounted for as a competing risk. The hazard ratio and P value were
calculated with the use of a Cox proportional-hazards model with a robust estimate of confidence limits according to the method of
Lin and Wei16 and the robust Wald test.
Cell contents are mean (SD) for time between measurements and absolute values of iothalamate GFR or difference (95%
confidence interval) for differences in iothalamate GFR within and between groups. Differences with confidence intervals and P
values are generated from the General Linear Model.
GFR was measured by iothalamate clearance periodically during the DCCT and at years 1 or 2 of EDIC (half of the cohort per year)
using standardized methods (Kidney Int 1995;47:1703-20). EDIC baseline is equivalent to DCCT closeout.
Results
Over a median follow-up period of 22 years in the combined
studies, impairment of the GFR developed in 24 participants
assigned to intensive therapy and in 46 assigned to conventional
therapy (risk reduction with intensive therapy, 50%; 95%
confidence interval, 18 to 69; P = 0.006). Among these
participants, end-stage renal disease developed in 8 participants
in the intensive-therapy group and in 16 in the
conventionaltherapy group. As compared with conventional
therapy, intensive therapy was associated with a reduction in the
mean estimated GFR of 1.7 ml per minute per 1.73 m2 during the
DCCT study but during the EDIC study was associated with a
slower rate of reduction in the GFR and an increase in the mean
estimated GFR of 2.5 ml per minute per 1.73 m2 (P<0.001 for
both comparisons). The beneficial effect of intensive therapy on
the risk of an impaired GFR was fully attenuated after adjustment
for glycated hemoglobin levels or albumin excretion rates.
Conclusions
The long-term risk of an impaired GFR was
significantly lower among persons treated
early in the course of type 1 diabetes with
intensive diabetes therapy than among
those treated with conventional diabetes
therapy.
(Funded by the National Institute of Diabetes and
Digestive and Kidney Diseases and others;
DCCT/EDIC ClinicalTrials.gov numbers, NCT00360815
and NCT00360893.)
Message/Comments
1型糖尿病患者1375人を対象に、血糖値正
常化を目指す強化療法と、高血糖症状を防
ぐ従来療法を無作為化試験で比較し、その
後の観察疫学研究で評価（DCCT/EDIC試
験）。平均22年の追跡期間の結果、糸球体
濾過率（GFR）低下の長期リスクは早期に
強化療法を受けた群で有意に低く、強化療
法によるリスク低下率は50%だった。