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埼玉医科大学　総合医療センター　内分泌・糖尿病内科埼玉医科大学　総合医療センター　内分泌・糖尿病内科Department of Endocrinology and Diabetes, Department of Endocrinology and Diabetes,

Saitama Medical Center, Saitama Medical UniversitySaitama Medical Center, Saitama Medical University

松田　昌文松田　昌文Matsuda, MasafumiMatsuda, Masafumi

20092009 年年 1010 月８日　月８日　 8:30-8:558:30-8:55８階　医局８階　医局

Landon MB, Spong CY, Thom E, Carpenter MW, Ramin SM, Casey B, Wapner RJ, Varner MW, Rouse DJ, Thorp JM Jr, Sciscione A, Catalano P, Harper M, Saade G, Lain KY, Sorokin Y, Peaceman AM, Tolosa JE, Anderson GB; Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network.A multicenter, randomized trial of treatment for mild gestational diabetes.N Engl J Med. 2009 Oct 1;361(14):1339-48.

Lasserson DS, Glasziou P, Perera R, Holman RR, Farmer AJ.Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta-analyses.Diabetologia. 2009 Oct;52(10):1990-2000. Epub 2009 Jul 31.

■ 症例 1■ 30 歳　女性■ 来院目的■　妊娠中の血糖管理■ 既往歴■　鬱病（ 28 歳より治療中），出産歴は経妊，経産ともなし。■ 生活習慣■　喫煙と飲酒はしない■ 家族歴■　特記事項なし■ 現病歴■

当院精神科通院中。妊娠 13 週より近くの産婦人科医院を通院し妊娠 19 週の 75g ブドウ糖負荷試験で空腹時血糖値 128mg/dl, 282mg/dl, 258mg/dl であった。血糖コントロール目的で妊娠 20 週で当科に紹介された。

■ 服薬■ 塩酸マプロチリン 100mg ( ルジオミール錠 １０ｍｇ 10 Ｔ ), レボメプロマジン 5mg (ヒルナミン錠 ５ｍｇ 1 Ｔ ), セチプチリンマレイン酸塩 6mg ( テシプール錠 １ｍｇ 6 Ｔ ), フルニトラゼパム 4mg ( サイレース錠 ２ｍｇ 2 Ｔ ), ブロマゼパム 4mg ( レキソタン錠 ２ｍｇ 2 Ｔ ), 以上１日量

■ 初診時現症■身長 155cm 、体重 82.2kg 　来院時血圧 118/73mmHg眼瞼結膜は貧血・黄疸無く，身体所見に異常は認めない。

■ 来院時（ 19 週）検査所見■血球数； RBC 451 万 /mm3, WBC 9400/m3, Hb 13.3g/dL, Hct 40.1%, Plt 24.8×104 /μl尿検査；糖 （－） , 蛋白 （－） , ケトン体 （－）生化学； T.P. 6.5g/dL, Alb 3.6g/dL., AST 17 I.U./l, ALT 10 I.U./l, T-Cho 199 mg/dl, HDL 82 mg/dl, TG 132 mg/dl, BUN 6 mg/dl, Crn 0.4 mg/dl, Na 135 mEq/l, K 4.0 mEq/l, Cl 103 mEq/l, PG 137 mg/dl ( 随時 ), HbA1c 7.1 %, グリコアルブミン 16.1 %眼底；異常なし

■問題１■ 妊娠前は糖尿病がなく妊娠を契機に血糖が上昇してきた症例です。妊娠継続と出産を強く希望されております。産婦人科医の判断は現時点では胎児に異常はなく妊娠継続は可能としています。次のうち初診時の説明として妥当なものはどれかa. 　予想される奇形率は５～１７％です。妊娠を継続し、出産に至った場合でも周産期の合併症の危険性は一般の２倍程度、帝王切開になる可能性は２０％程度と高くなります。b. 　妊娠中に血糖が上がると児が大きくなりすぎてしまうので治療が必要です。児への影響が無く、安全に治療できるインスリンで治療しましょう。c. 　体重は７ｋｇの増加までは問題ありません。妊娠中なので充分な栄養を摂り、体重を減らさないように注意してください。d. 　内服薬が多いので , 児に影響が出る可能性があります。このままでは授乳も出来ませんので一度中止して様子をみて無理なようなら中絶も考えましょう。

■問題２■25 週で受診した際のデータを示す。

体重 86.5kg 血圧 128/78mmHg

尿検査； 糖 （－） , 蛋白 （－） , ケトン体 （－）生化学； T.P. 6.2g/dL, Alb 3.4g/dL., AST 14 I.U./l, ALT 10 I.U./l, T-Cho 220 mg/dl, HDL 80 mg/dl, TG 222 mg/dl, BUN 8 mg/dl, Crn 0.5 mg/dl, Na 137 mEq/l, K 4.0 mEq/l, Cl 102 mEq/l, PG 86 mg/dl ( 随時 ), HbA1c 6.1 %, グリコアルブミン 10.5 %治療内容ノボラピッド（６０－５０－５０－　０）ノボリンＮ　（　０－　０－　０－１０）SMBG では空腹時 100mg/dl 以下、食後 2 時間血糖 120mg/dl 以下が達成できている。正しい対応はどれかa. 　血糖は改善しており、特に問題は無いことから単位数を変えずに引き続き外来で治療する。b. 　週数が進むにつれてインスリン量は増えるため、食後血糖が 120mg/dlを超えるようならインスリンを増やすように指導する。c. 　体重が増えすぎており、胎児死亡の危険性があるため入院のうえ食事とインスリンを調整する。d. 　体重増加は過食とインスリン過剰が原因なのでインスリンを減らして外来で治療する。

■問題１■ ■問題２■

Gestational diabetes is also diagnosed based on plasma glucose values measured during the OGTT. Blood glucose levels are checked four times during the test. If your blood glucose levels are above normal at least twice during the test, you have gestational diabetes. Table shows the above-normal results for the OGTT for gestational diabetes.

Table Gestational Diabetes: Above-Normal Results for the Oral Glucose Tolerance Test

When Plasma Glucose Result (mg/dL)

Fasting 95 or higher

At 1 hour 180 or higher

At 2 hours 155 or higher

At 3 hours 140 or higher

Frequency of Primary Outcomes across the Glucose Categories

The HAPO Study Cooperative Research Group. N Engl J Med 2008;358:1991-2002

Category 1 2 3 4 5 6 7FPG 74 or less 79 84 89 94 99 100 or more1hPG 105 or less 132 155 171 193 211 212 or more2hPG 90 or less 108 125 139 157 177 178 or more (mg/dl)

the Department of Obstetrics and Gynecology at Ohio State University, Columbus (M.B.L.); the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, MD (C.Y.S.); George Washington University Biostatistics Center, Washington, DC (E.T.); the Departments of Obstetrics and Gynecology at Brown University, Providence, RI (M.W.C.); University of Texas Health Science Center at Houston, Houston (S.M.R.); University of Texas Southwestern Medical Center, Dallas (B.C.); Columbia University, New York (R.J.W.); University of Utah, Salt Lake City (M.W.V.); University of Alabama at Birmingham, Birmingham (D.J.R.); University of North Carolina, Chapel Hill ( J.M.T.); Drexel University, Philadelphia (A.S.); Case Western Reserve University, Cleveland (P.C.); Wake Forest University Health Sciences, Winston- Salem, NC (M.H.); University of Texas Medical Branch, Galveston (G.S., G.B.A.); University of Pittsburgh, Pittsburgh (K.Y.L.); Wayne State University, Detroit (Y.S.); Northwestern University, Chicago (A.M.P.); and Oregon Health and Science University, Portland ( J.E.T.).

N Engl J Med 2009;361:1339-48.

AIMIt is uncertain whether treatment of mild gestational diabetes mellitus improves pregnancy outcomes.

MethodWomen who were in the 24th to 31st week of gestation and who met the criteria for mild gestational diabetes mellitus (i.e., an abnormal result on an oral glucose-tolerance test but a fasting glucose level below 95 mg per deciliter [5.3 mmol per liter]) were randomly assigned to usual prenatal care (control group) or dietary intervention, self-monitoring of blood glucose, and insulin therapy, if necessary (treatment group). The primary outcome was a composite of stillbirth or perinatal death and neonatal complications, including hyperbilirubinemia, hypoglycemia, hyperinsulinemia, and birth trauma.

Figure 1. Screening, Enrollment, Random Assignment, and Follow-up of the Study Participants.

To convert the values for glucose to millimoles per liter, multiply by 0.05551. OGTT denotes oral glucose tolerance test.

•Plus–minus values are means ±SD. Only alcohol use was significantly different between study groups (P=0.04). OGTT denotes oral glucose-tolerance test.

† Race or ethnic group was self-reported.

‡ The body-mass index is the weight in kilograms divided by the square of the height in meters.

§ To convert the values for glucose to millimoles per liter, multiply by

0.05551.

ResultsA total of 958 women were randomly assigned to a study group — 485 to the treatment group and 473 to the control group. We observed no significant difference between groups in the frequency of the composite outcome (32.4% and 37.0% in the treatment and control groups, respectively; P = 0.14). There were no perinatal deaths. However, there were significant reductions with treatment as compared with usual care in several prespecified secondary outcomes, including mean birth weight (3302 vs. 3408 g), neonatal fat mass (427 vs. 464 g), the frequency of large-for-gestational age infants (7.1% vs. 14.5%), birth weight greater than 4000 g (5.9% vs. 14.3%), shoulder dystocia (1.5% vs. 4.0%), and cesarean delivery (26.9% vs. 33.8%). Treatment of gestational diabetes mellitus, as compared with usual care, was also associated with reduced rates of preeclampsia and gestational hypertension (combined rates for the two conditions, 8.6% vs. 13.6%; P = 0.01).

ConclusionAlthough treatment of mild gestational diabetes mellitus did not significantly reduce the frequency of a composite outcome that included stillbirth or perinatal death and several neonatal complications, it did reduce the risks of fetal overgrowth, shoulder dystocia, cesarean delivery, and hypertensive disorders. (ClinicalTrials.gov number, NCT00069576.)

Message

妊娠糖尿病の場合にきちんと血糖管理する介入は大切である。

肥満の妊婦さんが増えているので注意！

Division of Public Health and Primary Care, University of Oxford, Rosemary Rue Building, Old Road Campus, Headington, Oxford OX3 7LF, UK

Diabetes Trials Unit, Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

Diabetologia (2009) 52:1990–2000

Aim

We compared the effect of biphasic, basal or prandial insulin regimens on glucose control, clinical outcomes and adverse events in people with type 2 diabetes.

MethodWe searched the Cochrane Library, MEDLINE, EMBASE and major American and European conference abstracts for randomised controlled trials up to October 2008. A systematic review and meta-analyses were performed.

Fig. 2 a–c Biphasic vs basal

change in HbA1c (%)

change in fasting SMBG

change in weight (kg)

WMD, weighted mean difference

Fig. 2 d–f Prandial vs basal WMD, weighted mean difference

change in HbA1c (%)

change in fasting SMBG

change in weight (kg)

ResultsTwenty-two trials that randomised 4,379 patients were included. Seven trials reported both starting insulin dose and titration schedules. Hypoglycaemia definitions and glucose targets varied. Meta-analyses were performed pooling data from insulin-naive patients. Greater HbA1c reductions were seen with biphasic and prandial insulin, compared with basal insulin, of 0.45% (95% CI 0.19–0.70, p=0.0006) and 0.45% (95% CI 0.16–0.73, p=0.002), respectively, but with lesser reductions of fasting glucose of 0.93 mmol/l (95% CI 0.21–1.65, p=0.01) and 2.20 mmol/l (95% CI 1.70–2.70, p<0.00001), respectively. Larger insulin doses at study end were reported in biphasic and prandial arms compared with basal arms. No studies found differences in major hypoglycaemic events, but minor hypoglycaemic events for prandial and biphasic insulin were inconsistently reported as either higher than or equivalent to basal insulin. Greater weight gain was seen with prandial compared with basal insulin (1.86 kg, 95% CI 0.80–2.92, p=0.0006).

Conclusion

Greater HbA1c reduction may be obtained in type 2 diabetes when insulin is initiated using biphasic or prandial insulin rather than a basal regimen, but with an unquantified risk of hypoglycaemia. Studies with longer follow-up are required to determine the clinical relevance of this finding.

Message

インスリンは血糖を下げる目的ならば、食後追加分泌補充は大切だが、低血糖に注意！

しかし、 HbA1cや空腹時血糖を目標に追加分泌を増やせば、当然低血糖は起こるのが当たり前！