Journal Club
Umpierrez GE, Smiley D, Hermayer K, Khan A, Olson DE,
Newton C, Jacobs S, Rizzo M, Peng L, Reyes D, Pinzon I, Fereira
ME, Hunt V, Gore A, Toyoshima MT, Fonseca VA.
Randomized Study Comparing a Basal Bolus With a Basal Plus
Correction Insulin Regimen for the Hospital Management of
Medical and Surgical patients With Type 2 Diabetes: Basal Plus
Trial.
Diabetes Care. 2013 Feb 22. [Epub ahead of print]
2013年3月28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
栗原 郁実
Kurihara, Ikumi
Medical ICUでの高血糖と死亡率
Surgical ICUでのインスリン強化療法による
死亡率減少
周術期（主に術後）には、
血糖を200mg/dl程度に
する治療に比較し
100mg/dl前後にすると
死亡率が半減する。
重症入院患者へのインスリン治療：死亡率
（無作為ランダム化研究のメタ解析）
周術期（主に術後）に
は、
血糖を200mg/dl程度に
する治療に比較し
100mg/dl前後にすると
死亡率が半減する。
心筋梗塞ではそれほど
の差はない。
35 publications, n=8478
最低血糖値と死亡
血糖スライディングをおこなっていた頃のデータ
0.18
0.16
0.14
死亡数
0.12
0.10
0.08
0.06
0.04
0.02
0.00
<30（49）
30-39（76）
>39（213）
入院中最低血糖値 （mg/dL）
米ブリガム・アンド・ウィメンズ病院（ボストン）などで、2003年1月から2004年8月に大学付属
病院へ入院した糖尿病患者2, 582例（入院4, 368回）についてレトロスペクティブに検討。最
低血糖値が10 mg/dL減少するごとに死亡リスクが3倍。
Diabetes Care 32: 1153–1157, 2009
低血糖は非常に危険
（病棟診療）
血糖スライディングスケールは「有効でなく使ってはいけな
い！」（米国糖尿病学会Clinical Practice Recommendation）
高血糖の場合には「補正量」を追加で使用
院内血糖管理ガイドライン
VIII. DIABETES CARE IN
SPECIFIC SETTINGS
A. Diabetes care in the hospital Recommendations
● Scheduled prandial insulin doses should be
appropriately timed in relation to meals and should be
adjusted according to point-of-care glucose levels. The
traditional sliding-scale insulin regimens are
ineffective as monotherapy and are generally not
recommended. (C)
● Using correction dose or "supplemental" insulin to
correct premeal hyperglycemia in addition to scheduled
prandial and basal insulin is recommended. (E)
DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S13
院内血糖管理ガイドライン
Diabetes care in the hospital Recommendations
● Scheduled subcutaneous insulin with basal, nutritional, and
correction components is the preferred method for
achieving and maintaining glucose control in noncritically
ill patients. (C) .
● Using correction dose or "supplemental" insulin to correct
premeal hyperglycemia in addition to scheduled prandial
and basal insulin is recommended. (E)
● Prolonged therapy with sliding scale insulin (SSI) as the
sole regimen is ineffective in the majority of patients,
increases risk of both hypoglycemia and hyperglycemia,
and has recently been shown to be associated with adverse
outcomes in general surgery patients with type 2 diabetes .
SSI is potentially dangerous in type 1 diabetes.
DIABETES CARE, VOLUME 35, SUPPLEMENT 1, JANUARY 2012
周術期，急性期の血糖管理
VIII. DIABETES CARE IN
SPECIFIC SETTINGS
A. Diabetes care in the hospital Recommendations
● All patients with diabetes admitted to the hospital should have
their diabetes clearly identified in the medical record. (E)
● Goals for blood glucose levels:
Critically ill surgical patients’ blood glucose levels should be
kept as close to 110 mg/dl (6.1 mmol/l) as possible and
generally 140 mg/dl (7.8 mmol/l). (A) These patients require
an intravenous insulin protocol that has demonstrated
efficacy and safety in achieving the desired glucose
Critically ill nonsurgical patients’ glycemic targets are less
well defined.
DIABETES CARE, VOLUME 32, SUPPLEMENT 1, JANUARY 2009 S13
周術期，急性期の血糖管理
VIII. DIABETES CARE IN
SPECIFIC SETTINGS
A. Diabetes care in the hospital Recommendations
● All patients with diabetes admitted to the hospital should have their
diabetes clearly identified in the medical record. (E)
Goals for blood glucose levels:
● Critically ill patients: Insulin therapy should be initiated for treatment
of persistent hyperglycemia starting at a threshold of no greater than
180 mg/dl (10 mmol/l). Once insulin therapy is started, a glucose
range of 140 –180 mg/dl (7.8 to 10 mmol/l) is recommended for the
majority of critically ill patients. (A) These patients require an
intravenous insulin protocol that has demonstrated efficacy and
safety in achieving the desired glucose range without increasing risk
for severe hypoglycemia. (E)
● Non–critically ill patients: BG＜140mg/dl (7.8 mmol/l) with random
blood glucose ＜180 mg/dl (10.0 mmol/l),
DIABETES CARE, VOLUME 33, SUPPLEMENT 1, JANUARY 2010 S13
•
•
•
•
•
•
•
•
•
シリンジポンプを用いたインスリン注入
による血糖管理のポイント
依頼のやり取り：看護師さんへの配慮
インスリン注入液準備
よく混和 49.5mlの生食
ブドウ糖[点滴、経管栄養]もポンプで注入
血糖管理はチームで交代で行う
インスリン注入率指示はこちらから電話
記録を残す
点滴や食事の開始/変更時の連絡
検査や処置で点滴や経管栄養中断に注意
血糖低下で次回70mg/dl以下になりそうであ
れば0.4U/hrに注入率を落とす
血糖による持続インスリン注入率の調節
とりあえず
血糖値÷100 ［単位/hr］ で開始
ボーラスは
上記÷６単位
300mg/dl
血糖による持続インスリン注入率の調節
安定してきたらΔで調節！
160mg/dl
210mg/dl
食事開始に伴うインスリン皮下注射
による血糖管理のポイント
• インスリン追加分泌補充は超速効型で食直後に
• 食事量スライディングスケールを用いる
（３分割：0-3，3-7，7-10割）
☆単位数が多い場合は４分割もある
（４分割：0-2，2-5，5-8，8-10割）
• 血糖補正を行う
目標血糖(120mg/dl)
１単位のインスリンで50mg/dl低下
• 基礎インスリン補充は朝，夕 中間型かレベミル２回から
開始(食事量が不明の場合)
• 点滴中でインスリン混注やシリンジポンプから注入中に
は基礎インスリン補充はしない
0000000
CASE 1
男
インスリン指示（食事開始後）
A basal-bolus insulin regimen is preferred over SSI.
care.diabetesjournals.org
the 1Department of Medicine, Division of Endocrinology, Emory University, Atlanta, Georgia; the
2Department of Medicine, Division of Endocrinology, Medical University of South Carolina,
Charleston, South Carolina; the 3Department of Medicine, Division of Endocrinology, Tulane
Medical Center, New Orleans, Louisiana; the 4Atlanta Veterans Affairs Medical Center, Decatur,
Georgia; the 5Department of Surgery, Emory University, Atlanta, Georgia; and the 6Rollins School
of Public Health, Emory University, Atlanta, Georgia.
Diabetes Care. 2013 Feb 22. [Epub ahead of print]
OBJECTIVE
Effective and easily implemented
insulin regimens are needed to facilitate
hospital glycemic control in general
medical and surgical patients with type
2 diabetes (T2D).
RESEARCH DESIGN AND METHODS
This multicenter trial randomized 375
patients with T2D treated with diet, oral
antidiabetic agents, or low-dose insulin
(≦0.4 units/kg/day) to receive a basal
bolus regimenwith glargine once daily
and glulisine before meals, a basal plus
regimen with glargine once daily and
supplemental doses of glulisine, and
sliding scale regular insulin (SSI).
We excluded patients with an
admission, patients with any
BG ＞400 mg/dL before
randomization or with a history
of hyperglycemic crises,
patients with hyperglycemia
without a known history of
diabetes, patients admitted to
or expected to require ICU
admission, patients
undergoing cardiac surgery,
patients receiving
corticosteroid therapy, patients
with clinically relevant hepatic
disease or impaired renal
function (serum creatinine ＞
3.0 mg/dL), patients with a
history of diabetic ketoacidosis,
pregnant patients, and
patients with any mental
condition rendering them
unable to give informed
consent.
1. Basal Bolus Regimen
1.A. Insulin Orders
Discontinue oral antidiabetic drugs and non-insulin injected antidiabetic medication on admission.
Starting insulin total daily dose (TDD): 0.5 units per kg of body weight.
Reduce insulin TDD to 0.3 units per kg of body weight in patients ≥ 70 years of age and/or with a serum creatinine ≥ 2.0 mg/dL.
Give half of total daily dose as insulin glargine and half as insulin glulisine.
Give insulin glargine once daily, at the same time of the day.
Give insulin glulisine in three equally divided doses before each meal. Hold insulin glulisine if patient not able to eat.
1.B. Supplemental insulin
Give supplemental insulin glulisine following the “sliding scale” protocol (1E) for blood glucose > 140 mg/dl.
If a patient is able and expected to eat all, give supplemental glulisine insulin before each meal and at bedtime following the
“usual” column.
If a patient is not able to eat, give supplemental glulisine insulin every 6 hours (6-12-6-12) following the “sensitive” column.
1.C. Insulin adjustment
If the fasting and predinner BG is between 100 - 140 mg/dl in the absence of hypoglycemia the previous day: no change
If the fasting and predinner BG is between 140 - 180 mg/dl in the absence of hypoglycemia the previous day: increase insulin
TDD by 10% every day
If the fasting and predinner BG is >180 mg/dl in the absence of hypoglycemia the previous day: increase insulin TDD dose by
20% every day
If the fasting and predinner BG is between 70 - 99 mg/dl in the absence of hypoglycemia: decrease insulin TDD dose by 10%
every day
If a patient develops hypoglycemia (BG <70 mg/dL), the insulin TDD should be decreased by 20%.
1.D. Blood glucose monitoring. Blood glucose will be measured before each meal and at bedtime (or every 6 hours if a patient is
not eating) using a glucose meter
1.E. Supplemental Insulin Scale
Blood Glucose (mg/dL)
Insulin Sensitive
Usual
Insulin Resistant
141-180
2
4
6
181-220
4
6
8
221-260
6
8
10
261-300
8
10
12
301-350
10
12
14
351-400
12
14
16
> 400
14
16
18
** Check appropriate column below and cross out other columns
The numbers in each column indicate the number of units of glulisine or regular insulin per dose. Supplemental” dose is to be added
to the scheduled dose of glulisine or regular insulin.
2. Basal Plus Regimen
2.A. Insulin Orders
Discontinue oral antidiabetic drugs and non-insulin injected antidiabetic medication on admission.
Starting glargine insulin total daily dose (TDD): 0.25 units per kg of body weight.
Reduce insulin TDD to 0.15 units per kg of body weight in patients ≥ 70 years of age and/or with a serum creatinine ≥ 2.0 mg/dL.
Give insulin glargine once daily, at the same time of the day.
2.B. Supplemental insulin
Give supplemental insulin glulisine following the “sliding scale” protocol (1E) for blood glucose > 140 mg/dl.
If a patient is able and expected to eat all, give supplemental glulisine insulin before each meal and at bedtime following the
“usual” column.
If a patient is not able to eat, give supplemental glulisine insulin every 6 hours (6-12-6-12) following the “sensitive” column.
2.C. Insulin adjustment
If the fasting and predinner BG is between 100 - 140 mg/dl in the absence of hypoglycemia the previous day: no change
If the fasting and predinner BG is between 140 - 180 mg/dl in the absence of hypoglycemia the previous day: increase glargine
TDD by 10% every day
If the fasting and predinner BG is >180 mg/dl in the absence of hypoglycemia the previous day: increase glargine TDD dose by
20% every day
If the fasting and predinner BG is between 70 - 99 mg/dl in the absence of hypoglycemia: decrease glargine TDD dose by 10%
every day
If a patient develops hypoglycemia (BG <70 mg/dL), the glargine TDD should be decreased by 20%.
2.D. Blood glucose monitoring. Blood glucose will be measured before each meal and at bedtime (or every 6 hours if a patient is
not eating) using a glucose meter
2.E. Supplemental Insulin Scale
Blood Glucose (mg/dL)
Insulin Sensitive
Usual Insulin
Resistant
141-180
2
4
6
181-220
4
6
8
221-260
6
8
10
261-300
8
10
12
301-350
10
12
14
351-400
12
14
16
> 400
14
16
18
** Check appropriate column below and cross out other columns
The numbers in each column indicate the number of units of glulisine insulin per dose.
Supplemental” dose is to be added to the scheduled dose of glulisine or regular insulin.
3. Regular Insulin By Sliding Scale
3.A. Insulin Orders
Discontinue oral antidiabetic drugs and non-insulin injected antidiabetic medication on admission.
Patients who are not eating or with intermittent nutritional intake
If a patient is not able to eat or if the nutritional intake is uncertain/intermittent, regular insulin will be administered every 6 hours
following the “insulin sensitive”
recommended dose of the sliding scale protocol (2D).
Patients who are eating
If a patient is able and expected to eat most of his/her meals, regular insulin will be administered before each meal and at
bedtime following the “usual” recommended dose of the sliding scale protocol.
3.B. Insulin adjustment
If the fasting and pre-meal plasma glucose are persistently >140 mg/dL in the absence of hypoglycemia, the insulin scale of
regular insulin could be increased from sensitive to usual, or from the usual to resistant scale.
If a patient develops hypoglycemia (blood glucose <60mg/dL), the sliding scale of regular insulin should be decreased from
insulin resistant to usual scale or from
the usual to sensitive scale.
3.C. Blood glucose monitoring. Blood glucose will be measured before each meal and at bedtime (or every 6 hours if a patient is
not eating) using a glucose meter.
3.D. Supplemental Insulin Scale
Blood Glucose (mg/dL)
Insulin Sensitive
Usual
Insulin Resistant
141-180
2
4
6
181-220
4
6
8
221-260
6
8
10
261-300
8
10
12
301-350
10
12
14
351-400
12
14
16
> 400
14
16
18
** Check appropriate column below and cross out other columns
The numbers in each column indicate the number of units of glulisine insulin per dose.
Supplemental” dose is to be added to the scheduled dose of glulisine or regular insulin.
Figure 1
Differences in
glycemic control in
medical and surgical
patients with T2D
treated with basal
bolus (C) and basal
plus (○) regimens.
A:Mean daily BG
levels.
B:Mean BG levels
before meals and
bedtime.
RESULTS
Improvement in mean daily blood glucose (BG) after
the first day of therapy was similar between basal
bolus and basal plus groups (P = 0.16), and both
regimens resulted in a lower mean daily BG than did
SSI (P = 0.04). In addition, treatment with basal bolus
and basal plus regimens resulted in less treatment
failure (defined as ＞2 consecutive BG＞240 mg/dL or
a mean daily BG＞240 mg/dL) than did treatment with
SSI (0 vs. 2 vs. 19%, respectively; P＜0.001). A BG ＜
70 mg/dL occurred in 16% of patients in the basal
bolus group, 13% in the basal plus group, and 3% in
the SSI group (P = 0.02). There was no difference
among the groups in the frequency of severe
hypoglycemia (＜ 40 mg/dL; P = 0.76).
CONCLUSIONS
The use of a basal plus regimen with
glargine once daily plus corrective
doses with glulisine insulin before
meals resulted in glycemic control
similar to a standard basal bolus
regimen. The basal plus approach is an
effective alternative to the use of a
basal bolus regimen in general medical
and surgical patients with T2D.
Message
病院内での血糖管理について,グラルギンが入っていれ
ば、食事の前の血糖で補正するのでOK?
（SSI［血糖スライディングスケール］は話にならないが…とい
うか血糖が下がっていない。／下げるほどやると低血糖になる
ので倫理委員会を通らないということかもしれないが。また、
glargineベースというのもどうかと感じる。また眠前血糖測定
でインスリンを打つのか？？？）
今回の補正量計算の表は現実とは異なる。また低血糖
についても今後評価が必要であろう。日本人ではこう
ならないと感じる。また心臓手術後やステロイド使用
者では？そもそも除外している。
また食直後打ちは有力で、glulisineであれば米国や
ヨーロッパでは薬剤の説明にあるはず。
サノフィ社と精度の悪いPOC器の会社が利益を得そう!?