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
Bergenstal RM, Klonoff DC, Garg SK, Bode BW, Meredith M, Slover RH,
Ahmann AJ, Welsh JB, Lee SW, Kaufman FR; the ASPIRE In-Home Study
Group.
Threshold-Based Insulin-Pump Interruption for Reduction of Hypoglycemia.
N Engl J Med. 2013 Jun 22. [Epub ahead of print]
Ziegler AG, Rewers M, Simell O, Simell T, Lempainen J, Steck A, Winkler C,
Ilonen J, Veijola R, Knip M, Bonifacio E, Eisenbarth GS.
Seroconversion to multiple islet autoantibodies and risk of progression to
diabetes in children.
JAMA. 2013 Jun 19;309(23):2473-9. doi: 10.1001/jama.2013.6285.
2013年7月4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
From the International Diabetes Center at Park Nicollet, Minneapolis (R.M.B.);
the Diabetes Research Institute, Mills–Peninsula Health Services, San Mateo
(D.C.K.), and Medtronic, Northridge (J.B.W., S.W.L., F.R.K.) — both in
California; the Barbara Davis Center for Childhood Diabetes, University of
Colorado Denver, Aurora (S.K.G., R.H.S.); Atlanta Diabetes Associates, Atlanta
(B.W.B.); Department of Medicine, University of Wisconsin, Madison (M.M.);
and the Harold Schnitzer Diabetes Health Center, Oregon Health and Science
University, Portland (A.J.A.).
N Engl J Med 2013. DOI: 10.1056/NEJMoa1303576
Background
The threshold-suspend feature of
sensor-augmented insulin pumps is
designed to minimize the risk of
hypoglycemia by interrupting insulin
delivery at a preset sensor glucose
value. We evaluated sensoraugmented insulin-pump therapy with
and without the threshold-suspend
feature in patients with nocturnal
hypoglycemia.
Methods
We randomly assigned patients with type 1
diabetes and documented nocturnal
hypoglycemia to receive sensor-augmented
insulin-pump therapy with or without the
threshold-suspend feature for 3 months. The
primary safety outcome was the change in the
glycated hemoglobin level. The primary
efficacy outcome was the area under the curve
(AUC) for nocturnal hypoglycemic events.
Two-hour threshold- suspend events were
analyzed with respect to subsequent sensor
glucose values.
MiniMed Paradigm Veo
http://www.diabetes-support.org.uk/info/?page_id=729
http://www.medtronic-diabetes.co.uk/product-information/paradigm-veo/index.html
Figure 2. Primary and Key Secondary End Points. As shown in Panel A,
the mean (±SD) changes in glycated hemoglobin concentrations during
the study phase (the primary safety end point) were similar in the
threshold-suspend and control groups (0.00±0.44% vs. −0.04±0.42%;
difference, 0.05 percentage points; 95% confidence interval [CI], −0.05 to
0.15). As shown in Panel B, the mean area under the curve (AUC) for
nocturnal hypoglycemic events during the study phase (the primary
efficacy end point) was 37.5% lower in the threshold-suspend group than
in the control group (P<0.001). As shown in Panel C, the percentage of
sensor glucose values that were less than 70 mg per deciliter was lower in
the thresholdsuspend group than in the control group, whether during
nighttime hours (6.0% vs. 10.0%) or during daytime and nighttime hours
combined (5.3% vs. 8.1%). The P value was less than 0.001 for each
range in the panel. (See Table S2 in the Supplementary Appendix for the
percentages of sensor glucose values in all ranges.) To convert values for
glucose to mmol per liter, multiply by 0.05551.
* The four reported serious adverse
events in the run-in phase were
radiculopathy resulting in
laminectomy in one patient,
coronary ischemia and stent
placement in one patient, coronary
artery disease in one patient, and
atypical chest pain in one patient.
† The two reported serious adverse
events in the study phase were
severe hypoglycemia in one patient
and pneumonia in one patient.
Results
A total of 247 patients were randomly assigned to receive sensoraugmented insulin pump therapy with the threshold-suspend feature
(threshold-suspend group, 121 patients) or standard sensor-augmented
insulin-pump therapy (control group, 126 patients). The changes in glycated
hemoglobin values were similar in the two groups. The mean AUC for
nocturnal hypoglycemic events was 37.5% lower in the threshold suspend
group than in the control group (980±1200 mg per deciliter [54.4±66.6
mmol per liter] × minutes vs. 1568±1995 mg per deciliter [87.0±110.7
mmol per liter] × minutes, P<0.001). Nocturnal hypoglycemic events
occurred 31.8% less frequently in the threshold-suspend group than in the
control group (1.5±1.0 vs. 2.2±1.3 per patient week, P<0.001). The
percentages of nocturnal sensor glucose values of less than 50 mg per
deciliter (2.8 mmol per liter), 50 to less than 60 mg per deciliter (3.3 mmol
per liter), and 60 to less than 70 mg per deciliter (3.9 mmol per liter) were
significantly reduced in the threshold-suspend group (P<0.001 for each
range). After 1438 instances at night in which the pump was stopped for 2
hours, the mean sensor glucose value was 92.6±40.7 mg per deciliter
(5.1±2.3 mmol per liter). Four patients (all in the control group) had a
severe hypoglycemic event; no patients had diabetic ketoacidosis.
Conclusions
This study showed that over a 3-month
period the use of sensor-augmented
insulinpump therapy with the thresholdsuspend feature reduced nocturnal
hypoglycemia, without increasing
glycated hemoglobin values.
(Funded by Medtronic MiniMed;
ASPIRE ClinicalTrials.gov number,
NCT01497938.)
Message
1型糖尿病患者247人を対象に、設定血糖値での
注入停止機能付きインスリンポンプの効果を無
作為化比較試験で評価（ASPIRE試験）。HbA1c値
の変化は、機能付き・機能なしの両ポンプ群で
同等だった。夜間低血糖イベントの平均曲線下
面積（AUC）は、機能なし群に比べ機能付きポン
プ群で37.5％小さかった（P＜0.001）。
Institute of Diabetes Research, Helmholtz Zentrum Mu¨nchen, and
Forschergruppe Diabetes, Klinikum rechts der Isar, Technische
Universita¨tMu¨nchen, Neuherberg, Germany (Drs Ziegler and
Winkler); Barbara Davis Center for Childhood Diabetes, University of
Colorado School of Medicine, Aurora (Drs Rewers, Steck, and
Eisenbarth); Department of Pediatrics (Drs O. Simell, T. Simell, and
Lempainen) and Immunogenetics Laboratory (Dr Lempainen and
Ilonen), University of Turku, and Department of Pediatrics, Turku
University Hospital (Drs O. Simell, T. Simell, and Lempainen), Turku,
Finland; Department of ClinicalMicrobiology, University of Eastern
Finland, Kuopio, Finland (Dr Ilonen); Department of Pediatrics,
Institute of Clinical Medicine, University of Oulu, Oulu, Finland (Dr
Veijola); Children’s Hospital, University of Helsinki and Helsinki
University Central Hospital, Helsinki, and Department of Pediatrics,
Tampere University Hospital, Tampere, Finland (Dr Knip); Center for
Regenerative Therapies Dresden, and Paul Langerhans Institute
Dresden, German Center for Diabetes Research, Dresden University
of Technology, Dresden, Germany (Dr Bonifacio).
JAMA. 2013;309(23):2473-2479
Importance Type 1 diabetes
usually has a preclinical phase
identified by circulating islet
autoantibodies, but the rate of
progression to diabetes after
seroconversion to islet
autoantibodies is uncertain.
Objective To determine the rate of
progression to diabetes after islet
autoantibody seroconversion.
Design, Setting, and Participants Data were pooled from
prospective cohort studies performed in Colorado
(recruitment, 1993-2006), Finland (recruitment, 1994- 2009),
and Germany (recruitment, 1989-2006) examining children
genetically at risk for type 1 diabetes for the development of
insulin autoantibodies, glutamic acid decarboxylase 65
(GAD65) autoantibodies, insulinoma antigen 2 (IA2)
autoantibodies, and diabetes. Participants were all children
recruited and followed up in the 3 studies (Colorado, 1962;
Finland, 8597; Germany, 2818). Follow-up assessment in
each study was concluded by July 2012.
Main Outcomes and Measures The primary analysis was
the diagnosis of type 1 diabetes in children with 2 or more
autoantibodies. The secondary analysis was the diagnosis of
type 1 diabetes in children with 1 autoantibody or no
autoantibodies.
Progression to type 1 diabetes at 10-year follow-up after islet autoantibody
seroconversion in 585 children with multiple islet autoantibodies was 69.7% (95%
CI, 65.1%-74.3%), and in 474 children with a single islet autoantibody was 14.5%
(95% CI, 10.3%-18.7%). Risk of diabetes in children who had no islet
autoantibodies was 0.4% (95% CI, 0.2%-0.6%) by the age of 15 years.
Results Progression to type 1 diabetes at 10-year follow-up after
islet autoantibody seroconversion in 585 children with multiple
islet autoantibodies was 69.7% (95% CI, 65.1%-74.3%), and in
474 children with a single islet autoantibody was 14.5% (95% CI,
10.3%-18.7%). Risk of diabetes in children who had no islet
autoantibodies was 0.4% (95% CI, 0.2%-0.6%) by the age of 15
years. Progression to type 1 diabetes in the children with multiple
islet autoantibodies was faster for children who had islet
autoantibody seroconversion younger than age 3 years (hazard
ratio [HR], 1.65 [95% CI, 1.30-2.09; P＜.001]; 10-year risk, 74.9%
[95% CI, 69.7%-80.1%]) vs children 3 years or older (60.9% [95%
CI, 51.5%-70.3%]); for children with the human leukocyte antigen
(HLA) genotype DR3/DR4-DQ8 (HR, 1.35 [95% CI, 1.09-1.68;
P=.007]; 10-year risk, 76.6% [95% CI, 69.2%-84%]) vs other HLA
genotypes (66.2% [95% CI, 60.2%-72.2%]); and for girls (HR,
1.28 [95% CI, 1.04-1.58; P=.02];10- year risk, 74.8% [95% CI,
68.0%-81.6%]) vs boys (65.7% [95% CI, 59.3%- 72.1%]).
Conclusions and Relevance
The majority of children at risk of
type 1 diabetes who had multiple
islet autoantibody
seroconversion progressed to
diabetes over the next 15 years.
Future prevention studies should
focus on this high-risk
population.
Message
ICA保有小児、15歳までにDM発症
前向きコホート研究3件（対象者1万3777
人）のデータを対象に、遺伝的な1型糖尿病
（DM）高リスク小児における膵島自己抗体
（ICA）へのセロコンバージョン後のDMへの
進行速度を検討。追跡調査10年間での発症
率は、複数ICA保有者で69.7％、単一保有者
で14.5％、非保有者の15歳までのDM発症リ
スクは0.4％だった。