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
Dutra Medeiros M, Mesquita E, Gardete-Correia L, Moita J, Genro V, Papoila AL, AmaralTurkman A, Raposo JF.
First Incidence and Progression Study for Diabetic Retinopathy in Portugal, the RETINODIAB
Study: Evaluation of the Screening Program for Lisbon Region.
Ophthalmology. 2015 Sep 14. pii: S0161-6420(15)00781-2. doi: 10.1016/j.ophtha.2015.08.004.
Bakris GL, Agarwal R, Chan JC, Cooper ME, Gansevoort RT, Haller H, Remuzzi G, Rossing P,
Schmieder RE, Nowack C, Kolkhof P, Joseph A, Pieper A, Kimmeskamp-Kirschbaum N,
Ruilope LM; Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy
(ARTS-DN) Study Group.
Effect of Finerenone on Albuminuria in Patients With Diabetic Nephropathy: A Randomized
Clinical Trial.
JAMA. 2015 Sep 1;314(9):884-94. doi: 10.1001/jama.2015.10081.
2015年10月8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
Microvascular Endpoints
15
Hazard ratio
10
p<0.0001
1
0.5
37% decrease per 1% decrement in HbA1c
0 5
6
7
8
9
10
11
Updated mean HbA1c
UKPDS 35. BMJ 2000; 321: 405-12
ukpds
1
Portuguese Diabetes Association, Lisbon, Portugal
2 Department of Ophthalmology, Central Lisbon Hospital Center, Lisbon, Portugal
3 NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
4 University of Minho, Braga, Portugal
5 Statistics and Informatics Department, NOVA Medical School, Universidade NOVA de Lisboa, Lisbon, Portugal
6 Epidemiology and Statistics Unit, Research Centre, Central Lisbon Hospital Center, Lisbon, Portugal
7 CEAUL (Center of Statistics and Applications); University of Lisbon, Lisbon, Portugal
8 Department of Statistics and Operational Research, Faculty of Sciences, University of Lisbon, Lisbon, Portugal
9 Department of Public Health/CEDOC (Chronic Diseases Research Center), NOVA Medical School, Universidade
NOVA de Lisboa, Lisbon, Portugal
Ophthalmology. 2015 Sep 14. pii: S0161-6420(15)00781-2. doi: 10.1016/j.ophtha.2015.08.004.
Purpose
To estimate the 5-year incidence and progression
of diabetic retinopathy (DR) among persons with
type 2 diabetes mellitus (DM).
Design
Population-based, prospective, cohort study.
Participants
The RETINODIAB (Study Group for Diabetic Retinopathy Screening) program
was implemented in the Lisbon and Tagus Valley area between July 2009 and
December 2014. A total of 109 543 readable screening examinations were
performed and corresponded to 56 903 patients who attended the screening
program at entry. A total of 30 641 patients (53.85%) had at least 1 further
screening event within the study period and were included in the analysis.
Methods
Participants underwent two 45°nonstereoscopic retinal digital photographs per
eye according to RETINODIAB protocol. All images were graded according to
the International Clinical Diabetic Retinopathy Scale. Referable diabetic
retinopathy (RDR) was defined for all patients graded as moderate
nonproliferative DR (NPDR), severe NPDR, or proliferative DR (PDR), with or
without maculopathy or mild NPDR with maculopathy. Nonparametric estimates
of the annual and cumulative incidences were obtained by Turnbull's estimator.
Associations between the potential risk factors and the time to
onset/progression of retinopathy were assessed through a parametric survival
analysis for interval-censored data.
Main Outcome Measures
The authors estimated the onset and progression incidence rates of DR.
科学的根拠に基づく糖尿病診療ガイドライン2013
http://www.med.teikyo-u.ac.jp/~ortho/med/dis/dis2/dmr.htm
Results
Yearly incidence of any DR in patients without retinopathy at
baseline was 4.60% (95% confidence interval [CI], 3.96–
4.76) in the first year, decreasing to 3.87% (95% CI, 2.57–
5.78) in the fifth year. In participants with mild NPDR at
baseline, the progression rate to RDR in year 1 was 1.18%
(95% CI, 0.96–1.33). Incidence of any DR and RDR and DR
progression rate were associated with known duration of
diabetes, age at diagnosis, and use of insulin treatment.
Conclusions
This longitudinal epidemiologic study provides the
first Portuguese incidence DR data in a largescale population-based cohort of type 2 diabetes
after a 5-year follow-up. Duration of diabetes, age
at diagnosis, and insulin treatment were
associated with increasing risk of incidence and
progression of DR. A personalized schedule
distribution of screening intervals according to the
individual patient's profile should be implemented,
with resulting benefits in terms of health costs.
Message
ポルトガルで2型糖尿病（DM）患者3万641人を対
象に、5年間の糖尿病性網膜症（DR）発症率と進
行率を集団ベースの前向きコホート研究で調査
（RETINODIAB試験）。ベースラインで非網膜症
だった患者のDR年間発症率は1年目4.60％（95％
CI, 3.96 - 4.76）、5年目3.87％（同2.57 5.78）だった。糖尿病罹病期間、診断時年齢、
インスリン治療がDR発症および進行リスク増加
と関連した。
http://www.m3.com/clinical/journal/15856
Spironolactone
Eplerenone
George L. Bakris, MD1; Rajiv Agarwal, MD2; Juliana C. Chan, MD3; Mark E. Cooper, MD, PhD4; Ron T. Gansevoort, MD, PhD5;
Hermann Haller, MD, PhD6; Giuseppe Remuzzi, MD7,8; Peter Rossing, MD9,10,11; Roland E. Schmieder, MD12; Christina
Nowack, MD13; Peter Kolkhof, PhD14; Amer Joseph, MBBS15; Alexander Pieper, DiplStat16; Nina Kimmeskamp-Kirschbaum,
PhD17; Luis M. Ruilope, MD, PhD18 ; for the Mineralocorticoid Receptor Antagonist Tolerability Study–Diabetic Nephropathy
(ARTS-DN) Study Group
1University
of Chicago Medicine, Chicago, Illinois
L. Roudebush VA Medical Center and Indiana University, Indianapolis
3Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong, China
4Baker IDI Heart and Diabetes Institute, Melbourne, Australia
5Department of Nephrology, University Medical Center Groeningen, Groeningen, the Netherlands
6Departments of Nephrology and Hypertension, Hannover Medical School, Hannover, Germany
7Istituto di Ricerche Farmacologiche Mario Negri, Clinical Research Center for Rare Diseases “Aldo e Cele Daccò,” Ranica (Bergamo), Italy
8Unit of Nephrology and Dialysis, Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, Italy
9Steno Diabetes Center, Gentofte, Denmark
10University of Copenhagen, Copenhagen, Denmark
11Aarhus University, Aarhus, Denmark
12Department of Nephrology and Hypertension, University Hospital Erlangen, Erlangen, Germany
13Global Clinical Development, Bayer HealthCare AG, Wuppertal, Germany
14Heart Diseases Research, Global Drug Discovery, Bayer HealthCare AG, Wuppertal, Germany
15Global Clinical Development, Bayer PLC, Newbury, England
16MARCO GmbH & Co KG, Düsseldorf, Germany
17Global Research and Development Statistics, Bayer HealthCare AG, Leverkusen, Germany
18Institute of Investigation and Hypertension Unit, Hospital 12 de Octubre, Madrid, Spain
2Richard
JAMA. 2015 Sep 1;314(9):884-94. doi: 10.1001/jama.2015.10081.
Importance Steroidal mineralocorticoid receptor
antagonists, when added to a renin-angiotensin
system blocker, further reduce proteinuria in
patients with chronic kidney disease but may be
underused because of a high risk of adverse
events.
Objective To evaluate the safety and efficacy of
different oral doses of the nonsteroidal
mineralocorticoid receptor antagonist finerenone,
given for 90 days to patients with diabetes and
high or very high albuminuria who are receiving
an angiotensin-converting enzyme inhibitor or an
angiotensin receptor blocker.
Design, Setting, and Participants Randomized, doubleblind, placebo-controlled, parallel-group study conducted
at 148 sites in 23 countries. Patients were recruited from
June 2013 to February 2014 and the study was completed
in August 2014. Of 1501 screened patients, 823 were
randomized and 821 received study drug.
Interventions Participants were randomly assigned to
receive oral, once-daily finerenone (1.25 mg/d, n = 96; 2.5
mg/d, n = 92; 5 mg/d, n = 100; 7.5 mg/d, n = 97; 10 mg/d,
n = 98; 15 mg/d, n = 125; and 25 mg/d, n = 119) or
matching placebo (n = 94) for 90 days.
Main Outcomes and Measures The primary outcome
was the ratio of the urinary albumin-creatinine ratio
(UACR) at day 90 vs at baseline. Safety end points were
changes from baseline in serum potassium and estimated
glomerular filtration rate.
Figure 1. Flowof Participants in the
Mineralocorticoid Receptor Antagonist
Tolerability Study–Diabetic
Nephropathy
Results The mean age of the participants was 64.2 years; 78% were
male. At baseline, 36.7% of patients treated had very high
albuminuria (UACR ≥300 mg/g) and 40.0% had an estimated
glomerular filtration rate of 60 mL/min/1.73 m2 or lower. Finerenone
demonstrated a dose-dependent reduction in UACR. The primary
outcome, the placebo-corrected mean ratio of the UACR at day 90
relative to baseline, was reduced in the finerenone 7.5-, 10-, 15-, and
20-mg/d groups (for 7.5 mg/d, 0.79 [90% CI, 0.68-0.91; P = .004]; for
10 mg/d, 0.76 [90% CI, 0.65-0.88; P = .001]; for 15 mg/d, 0.67 [90%
CI, 0.58-0.77; P<.001]; for 20 mg/d, 0.62 [90% CI, 0.54-0.72;
P < .001]). The prespecified secondary outcome of hyperkalemia
leading to discontinuation was not observed in the placebo and
finerenone 10-mg/d groups; incidences in the finerenone 7.5-, 15-,
and 20-mg/d groups were 2.1%, 3.2%, and 1.7%, respectively. There
were no differences in the incidence of the prespecified secondary
outcome of an estimated glomerular filtration rate decrease of 30% or
more or in incidences of adverse events and serious adverse events
between the placebo and finerenone groups.
Conclusions and Relevance Among patients
with diabetic nephropathy, most receiving an
angiotensin-converting enzyme inhibitor or an
angiotensin receptor blocker, the addition of
finerenone compared with placebo resulted in
improvement in the urinary albumin-creatinine
ratio. Further trials are needed to compare
finerenone with other active medications.
Trial Registration clinicaltrials.gov Identifier:
NCT1874431
Message
糖尿病性腎症でACE阻害薬またはARB治療中の821
人を対象に、非ステロイド性鉱質コルチコイド
受容体拮抗薬finerenoneの併用効果を無作為化
試験で検証。90日後、7.5、10、15、20mg/日群
で尿中アルブミン/クレアチニン比（AER）が低
下した（プラセボ補正後のベースラインに対す
る比0.79［90％ CI, 0.68 - 0.91；P＝0.004］、
0.76［90％ CI, 0.65 - 0.88；P＝0.001］、
0.67［90％ CI, 0.58 - 0.77；P＜0.001］、
0.62［90％ CI, 0.54 - 0.72；P＜0.001］）。
https://www.m3.com/clinical/journal/15821

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