Transcript PowerPoint プレゼンテーション - 埼玉医科大学総合医療センター 内分泌

Journal Club
Zhang X, Saaddine JB, Chou CF, Cotch MF, Cheng YJ, Geiss LS, Gregg EW, Albright
AL, Klein BE, Klein R.
Prevalence of diabetic retinopathy in the United States, 2005-2008.
JAMA. 2010 Aug 11;304(6):649-56.
Ronald CW Ma, Claudia HT Tam, Ying Wang, Andrea O Luk, Cheng Hu, Xilin Yang,
Vincent Lam, Alfred WH Chan, Janice SK Ho, Chun-Chung Chow, Peter CY Tong,
Weiping Jia, Maggie CY Ng, Wing-Yee So, Juliana CN Chan
Genetic variants of the protein kinase c-b1 gene and development of end-stage renal
disease in patients with type 2 diabetes
JAMA. 2010 Aug 25;304(8):881-889.
2010年8月26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
1991年7月(平成3年)発表　昭和63年度
日本の人口　x1,000人
障害者手帳を新規に交付された18歳以上の視覚障害者15,893名
63
1988
122,745
８県の視覚障害者2,161名を対象
平成元年 1989
123,205
推定障害者数
%
2
1990 a)123,611
糖尿病網膜症
2,986
18.3
3
1991
124,101
白内障
2,549
15.6
4
1992
124,567
緑内障
2,360
14.5
5
1993
124,938
網膜色素変性症
1,991
12.2
6
1994
125,265
高度近視
1,749
10.7
7
1995 a)125,570
視神経・網脈絡膜萎縮
1,591
9.8
8
1996
125,859
その他
2,667
18.9
9
1997
126,157
合計
15,893
100.0
10
1998
126,472
11
1999
126,667
平成17年度(2005年度)研究報告　最近１年
12
2000 a)126,926
視覚障害新規認定者2,034名
13
2001
127,316
（全国新規交付総数に対する抽出比率は12.4％）
14
2002
127,486
推定障害者数
%
15
2003
127,694
緑内障
3,395
20.7
16
2004
127,787
糖尿病網膜症
3,117
19.0
17
2005
127,768
網膜色素変性症
2,247
13.7
18
2006
127,770
黄斑変性症
1,493
9.1
19
2007
127,771
高度近視
1,279
7.8
20
2008
127,692
その他
4,872
29.7
合計
16,403
100.0
a)　国勢調査人口
Division of Diabetes Translation, National Center for
Chronic Disease Prevention and Health Promotion,
Centers for Disease Control and Prevention, Atlanta,
Georgia (Drs Zhang, Saaddine, Chou, Cheng, Geiss,
Gregg, and Albright); Division of Epidemiology and
Clinical Applications, National Eye Institute, National
Institutes of Health, Bethesda, MD (Dr Cotch);
Department of Ophthalmology and Visual Sciences,
University of Wisconsin, School of Medicine and Public
Health, Madison, Wisconsin (Drs B. Klein and R. Klein)
JAMA. 2010;304(6):649-656
DIABETIC RETINOPATHY IS THE leading cause of
new cases of legal blindness among adults aged 20
to 74 years in the United States.
Klein R, Klein B. Vision disorders in diabetes. In: National
Diabetes Data Group, ed. Diabetes in America. 2nd ed.
Bethesda, MD: National Institutes of Health, National
Institute of Diabetes and Digestive and Kidney Diseases;
1995:293–337.
1988-1994 (National Health and Nutrition Examination Surveys III [NHANES III]).
Background
Context The prevalence of diabetes in the
United States has increased. People with
diabetes are at risk for diabetic retinopathy.
No recent national population-based
estimate of the prevalence and severity of
diabetic retinopathy exists.
Objectives To describe the prevalence
and risk factors of diabetic retinopathy
among US adults with diabetes aged 40
years and older.
Methods
Design, Setting, and Participants Analysis of a crosssectional, nationally representative sample of the National
Health and Nutrition Examination Survey 2005-2008
(N=1006). Diabetes was defined as a self-report of a
previous diagnosis of the disease (excluding gestational
diabetes mellitus) or glycated hemoglobin A1c of 6.5% or
greater. Two fundus photographs were taken of each eye
with a digital nonmydriatic camera and were graded using
the Airlie House classification scheme and the Early
Treatment Diabetic Retinopathy Study severity scale.
Prevalence estimates were weighted to represent the
civilian, non institutionalized US population aged 40 years
and older.
Main Outcome Measurements Diabetic retinopathy and
vision-threatening diabetic retinopathy.
Vision-threatening diabetic retinopathy, a level
that may soon result in vision loss if left untreated,
was defined as the presence of severe non
proliferative diabetic retinopathy, proliferative
diabetic retinopathy, or clinically significant
macular edema.
Results
Results The estimated prevalence of diabetic retinopathy and visionthreatening diabetic retinopathy was 28.5% (95% confidence interval
[CI], 24.9%-32.5%) and 4.4% (95% CI, 3.5%-5.7%) among US adults
with diabetes, respectively. Diabetic retinopathy was slightly more
prevalent among men than women with diabetes (31.6%; 95% CI,
26.8%-36.8%; vs 25.7%; 95% CI, 21.7%-30.1%; P=.04). Non- Hispanic
black individuals had a higher crude prevalence than non-Hispanic
white individuals of diabetic retinopathy (38.8%; 95% CI, 31.9%-46.1%;
vs 26.4%; 95% CI, 21.4%-32.2%; P=.01) and vision-threatening
diabetic retinopathy (9.3%; 95% CI, 5.9%-14.4%; vs 3.2%; 95% CI,
2.0%-5.1%; P=.01). Male sex was independently associated with the
presence of diabetic retinopathy (odds ratio [OR], 2.07; 95% CI, 1.393.10), as well as higher hemoglobin A1c level (OR, 1.45; 95% CI, 1.201.75), longer duration of diabetes (OR, 1.06 per year duration; 95% CI,
1.03-1.10), insulin use (OR, 3.23; 95% CI, 1.99-5.26), and higher
systolic blood pressure (OR, 1.03 per mm Hg; 95% CI, 1.02-1.03).
Conclusion
Conclusion In a nationally
representative sample of US adults
with diabetes aged 40 years and older,
the prevalence of diabetic retinopathy
and vision-threatening diabetic
retinopathy was high, especially
among Non-Hispanic black individuals.
Message/Comments
米国で糖尿病性網膜症の疫学データはサン
プリングだが眼底写真を撮っている。
失明がどのくらいか不明だが米国では糖尿
病患者の４～５％が失明の危険性のある網
膜症というのはかなりショックなデータ。
Activation of PKC in diabetic kidney
by hyperglycemia leading to multiple
pathological changes in diabetic
nephropathy
Ruboxistaurin: LY 333531
Fundamental & Clinical Pharmacology 22 (2008) 231–240
Protein kinase C, beta 1
LY333531 administration in diabetic rats resulted in near normalization of GFR and
filtration fraction.
Use of PKC b inhibitor in a small patient population of type 2 DN showed a significant
reduction in albuminuria, prevented loss of eGFR and improvement in renal function
A new drug application seeking approval from USA-FDA for ruboxistaurin for the treatment of moderate to severe non-proliferative
diabetic retinopathy was submitted by Eli Lilly in February 2006. Lilly received an approval letter from the FDA in August, 2006. FDA
requested additional 3-year, phase 3 clinical trial to provide additional efficacy data before approving the drug in moderate to severe
non-proliferative retinopathy.
17 April 2007 The manufacturer of ruboxistaurin has advised us that they have withdrawn regulatory applications in relation to this
product at this time. The Institute has therefore decided to remove this appraisal from its work programme.
Department of Medicine and Therapeutics (Drs Ma, Wang, Luk,
Yang, Chow, Tong, Ng, So, and J. Chan; Mss Tam and Ho; and
Messrs Lam and A. Chan), Hong Kong Institute of Diabetes and
Obesity (Drs Ma and J. Chan), and Li Ka Shing Institute of Health
Sciences (Dr J. Chan), Chinese University of Hong Kong, Prince
of Wales Hospital, Shatin, New Territories, Hong Kong SAR,
China; and Department of Endocrinology and Metabolism,
Shanghai Clinical Center of Diabetes, Shanghai Jiaotong
University Affiliated Sixth People’s Hospital, Shanghai Diabetes
Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai,
China (Drs Hu and Jia). Dr Ng is now with Department of
Pediatrics, Section on Medical Genetics, Centers for Diabetes
Research and Human Genomics, Wake Forest University School
of Medicine, Winston-Salem, North Carolina.
JAMA. 2010;304(8):881-889
Background
Context Protein kinase C-β (PKC-β) is a
cell-signaling intermediate implicated in
development of diabetic complications.
Objective To examine the risk association
of PKC- β1 gene (PRKCB1)
polymorphisms and end-stage renal
disease (ESRD) in an 8-year prospective
cohort of Chinese patients with type 2
diabetes.
Methods
Design, Setting, and Participants We genotyped 18
common tag single nucleotide polymorphisms (SNPs)
that span the PRKCB1 gene (r2=0.80) in 1172 Chinese
patients (recruited 1995-1998) without renal disease at
baseline. A validation cohort included an additional 1049
patients with early-onset diabetes who were free of
renal disease at baseline and were recruited after 1998.
Main Outcome Measures Associations of PRKCB1
polymorphisms under additive, dominant, and recessive
genetic models with new onset of ESRD (defined as
estimated glomerular filtration rate<15 mL/min/1.73m2
or dialysis or renal-related death) were assessed by
Cox proportional hazard regression, adjusted for all
conventional risk factors including use of medications
Adjusted for mean values of sex, age,
duration of diabetes, systolic and
diastolic blood pressure, hemoglobin
A1c, total cholesterol, natural logarithm
of triglycerides, estimated glomerular
filtration rate, natural logarithm of
albumin excretion rate, retinopathy
(present/absent),and use of medications
(yes/no). Three significant and
independent single-nucleotide
polymorphisms with r2<0.80 (rs3760106
with the dominant model, rs7404928
with the recessive model, and
rs4787733 with the additive model)
were selected to calculate the number
of risk alleles for end-stage renal
disease (ESRD).
Results
Results After a mean (SD) of 7.9 (1.9) years, 90 patients (7.7%) progressed to
ESRD. Four common SNPs were associated with ESRD (P<.05). The closely
linked T allele at rs3760106 and G allele rs2575390 (r2=0.98) showed the
strongest association with ESRD (hazard ratio [HR], 2.25; 95% confidence
interval [CI], 1.31-3.87; P=.003, and HR, 2.26; 95% CI, 1.31-3.88; P=.003,
respectively). Four common variants predicted ESRD in separate models. The
HR for ESRD increased with increasing number of risk alleles (P<.001) in the
joint effect analysis. The adjusted risk for ESRD was 6.04 (95% CI, 2.00-18.31)
for patients with 4 risk alleles compared with patients with 0 or 1 risk allele.
Incidence was 4.4 per 1000 person-years (95% CI, 0.5-8.2) among individuals
with 0 or 1 risk allele compared with 20.0 per 1000 person-years (95% CI, 8.831.1) in those carrying 4 risk alleles (6.9% of the cohort). These results were
validated in a separate prospective cohort of young-onset diabetic patients. Of
1049 patients in the validation cohort, 151 (14.3%) developed chronic kidney
disease (CKD) during follow-up, and there were significant associations
between both the T allele of rs3760106 and the G allele of rs2575390 and
development of CKD (HR, 1.68; 95% CI, 1.10-2.57; P=.02, and HR, 1.62; 95%
CI, 1.07-2.47; P=.02, respectively).
Conclusion
Conclusion Genetic variants in the
PRKCB1 gene were independently
associated with development of ESRD in
Chinese patients with type 2 diabetes.
Message
PKC-b1が網膜症や腎症に重要な役割をすること
はよく知られている。
糖尿病性腎症進展のリスクとしてこの遺伝子多
型が関与することは意義があるが、PKC-b1阻害
薬の開発はどうなっているのだろうか？
日本での同様な研究
Araki S, Haneda M, Sugimoto T, et al. Polymorphisms of the protein kinase C-beta
gene (PRKCB1) accelerate kidney disease in type 2 diabetes without overt
proteinuria. Diabetes Care. 2006;29(4):864-868.
T allele at 1054 C/T and G allele at 546 C/G