日本糖尿病学会：Q17-3妊婦の糖代謝異常をどのようにスクリーニングするか？．糖尿病診療ガイドライン2019. 南江堂、2019；p287.
日本産科婦人科学会, 日本産婦人科医会：CQ005-1妊婦の糖代謝異常スクリーニングと診断のための検査は？, 産婦人科診療ガイドライン産科編2023．日本産科婦人科学会事務局、2023；p20-22.
Shlomit Riskin-Mashiah, Grace Younes, Amit Damti, Ron Auslender
First-trimester fasting hyperglycemia and adverse pregnancy outcomes.
Diabetes Care. 2009 Sep;32(9):1639-43. doi: 10.2337/dc09-0688. Epub 2009 Jun 23.
Abstract/Text
OBJECTIVE: The Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study found strong associations between higher levels of maternal glucose at 24-32 weeks, within what is currently considered normoglycemia and adverse pregnancy outcomes. Our aim was to evaluate the associations between first-trimester fasting plasma glucose level and adverse pregnancy outcomes.
RESEARCH DESIGN AND METHODS: Charts of all patients who delivered at our hospital between June 2001 and June 2006 were reviewed. Only subjects with singleton pregnancy and a recorded first-trimester fasting glucose level were included. Women with pregestational diabetes, fasting glucose level >105 mg/dl, or delivery <24 weeks were excluded. Fasting glucose levels were analyzed in seven categories, similar to the HAPO study. The main outcomes were development of gestational diabetes mellitus (GDM), large-for-gestational-age (LGA) neonates and/or macrosomia, and primary cesarean section. Multivariate logistic regression analysis was used; significance was <0.05.
RESULTS: A total of 6,129 women had a fasting glucose test at median of 9.5 weeks. There were strong, graded associations between fasting glucose level and primary outcomes. The frequency of GDM development increased from 1.0% in the lowest glucose category to 11.7% in the highest (adjusted odds ratio 11.92 [95% CI 5.39-26.37]). The frequency of LGA neonates and/or macrosomia increased from 7.9 to 19.4% (2.82 [1.67-4.76]). Primary cesarean section rate increased from 12.7 to 20.0% (1.94 [1.11-3.41]).
CONCLUSIONS: Higher first-trimester fasting glucose levels, within what is currently considered a nondiabetic range, increase the risk of adverse pregnancy outcomes. Early detection and treatment of women at high risk for these complications might improve pregnancy outcome.
M E Griffin, M Coffey, H Johnson, P Scanlon, M Foley, J Stronge, N M O'Meara, R G Firth
Universal vs. risk factor-based screening for gestational diabetes mellitus: detection rates, gestation at diagnosis and outcome.
Diabet Med. 2000 Jan;17(1):26-32.
Abstract/Text
AIMS: Gestational diabetes mellitus (GDM) is associated with adverse maternal and fetal outcome. Screening for GDM is therefore recommended but the best screening method remains controversial. This prospective, randomized study compared a risk factor-based screening programme with a universally based one.
METHODS: Subjects were randomized at booking to one of two groups: the risk factor group had a 3-h 100-g oral glucose tolerance test (OGTT) at 32 weeks if any risk factor for GDM was present; the universal group had a 50-g glucose challenge test performed and if their plasma glucose at 1 h was > or = 7.8 mmol/l, a formal 3-h 100-g OGTT was then performed.
RESULTS: Universal screening detected a prevalence of GDM of 2.7%, significantly more than the 1.45% detected in the risk factor screened group (P<0.03). Universal screening facilitated earlier diagnosis than risk factor screening - mean gestation 30 +/- 2.6 weeks vs. 33 +/- 3.7 weeks (P<0.05). A higher rate of spontaneous vaginal delivery at term, and lower rates of macrosomia, Caesarean section, prematurity, pre-eclampsia and admission to neonatal intensive care unit were observed in the universally screened, early diagnosis group.
CONCLUSIONS: Universal screening for GDM is superior to risk factor based screening-detecting more cases, facilitating early diagnosis and is associated with improved pregnancy outcome.
日本糖尿病・妊娠学会と日本糖尿病学会との合同委員会（平松祐司、羽田勝計）：妊娠中の糖代謝異常と診断基準の統一化について．日本産婦人科学会雑誌．2015;67:1656-8.
日本糖尿病学会：Q17-5糖代謝異常妊婦の妊娠中管理目標はどう設定すべきか？．糖尿病診療ガイドライン2019. 南江堂、2019；p291-294.
U Hanson, B Persson, S Thunell
Relationship between haemoglobin A1C in early type 1 (insulin-dependent) diabetic pregnancy and the occurrence of spontaneous abortion and fetal malformation in Sweden.
Diabetologia. 1990 Feb;33(2):100-4. doi: 10.1007/BF00401047.
Abstract/Text
This prospective nationwide study examined the relationship between diabetic control in early pregnancy as assessed by HbA1C and the incidence of spontaneous abortion and fetal malformation. HbA1C and plasma C-peptide were determined in 532 women with Type 1 (insulin-dependent) diabetes mellitus, corresponding to approximately 80% of all the diabetic pregnancies in the country during the study period 1982-1985, and 222 non-diabetic control women. Median gestational week for sampling was 9.0 in the Type 1 diabetic and 10.0 in the control group. The median value of HbA1C was 7.7% in the diabetic and 5.3% in the control group (p less than 0.001). The rates of spontaneous abortion, 7.7% vs 7.2%, and malformation, 4.3% (major 2.0%) and 2.4% (major 1.0%), were not significantly different between the diabetic and control group, respectively. These rates of malformation were not significantly different from the national figures of 4.55% (major 1.75%). Much elevated HbA1C, i.e., greater than 10.1% equal to 8 SD above the normal mean control value, was significantly associated with the occurrence of spontaneous abortion (p less than 0.001) and malformation (p less than 0.01). Discriminant analysis revealed that after correction had been made for the significant value of HbA1C to predict the occurrence of spontaneous abortion and malformation, no further predictive power was displayed by measurable plasma C-peptide, maternal age or duration of diabetes or presence of diabetic microangiopathy. We conclude that poor metabolic control in early pregnancy contributes to an increased risk of both spontaneous abortion and fetal malformation.
Hayfaa A Wahabi, Rasmeia A Alzeidan, Ghada A Bawazeer, Lubna A Alansari, Samia A Esmaeil
Preconception care for diabetic women for improving maternal and fetal outcomes: a systematic review and meta-analysis.
BMC Pregnancy Childbirth. 2010 Oct 14;10:63. doi: 10.1186/1471-2393-10-63. Epub 2010 Oct 14.
Abstract/Text
BACKGROUND: Preexisting diabetes mellitus is associated with increased risk for maternal and fetal adverse outcomes. Despite improvement in the access and quality of antenatal care recent population based studies demonstrating increased congenital abnormalities and perinatal mortality in diabetic mothers as compared to the background population. This systematic review was carried out to evaluate the effectiveness and safety of preconception care in improving maternal and fetal outcomes for women with preexisting diabetes mellitus.
METHODS: We searched the following databases, MEDLINE, EMBASE, WEB OF SCIENCE, Cochrane Library, including the CENTRAL register of controlled trials and CINHAL up to December 2009, without language restriction, for any preconception care aiming at health promotion, glycemic control and screening and treatment of diabetes complications in women of reproductive age group with type I or type II diabetes. Study design were trials (randomized and non-randomized), cohort and case-control studies. Of the 1612 title scanned 44 full papers were retrieved of those 24 were included in this review. Twelve cohort studies at low and medium risk of bias, with 2502 women, were included in the meta-analysis.
RESULTS: Meta-analysis suggested that preconception care is effective in reducing congenital malformation, RR 0.25 (95% CI 0.15-0.42), NNT17 (95% CI 14-24), preterm delivery, RR 0.70 (95% CI 0.55-0.90), NNT = 8 (95% CI 5-23) and perinatal mortality RR 0.35 (95% CI 0.15-0.82), NNT = 32 (95% CI 19-109). Preconception care lowers HbA1c in the first trimester of pregnancy by an average of 2.43% (95% CI 2.27-2.58). Women who received preconception care booked earlier for antenatal care by an average of 1.32 weeks (95% CI 1.23-1.40).
CONCLUSION: Preconception care is effective in reducing diabetes related congenital malformations, preterm delivery and maternal hyperglycemia in the first trimester of pregnancy.
末原節代、和栗雅子 他：当センターにおける糖代謝異常妊婦の頻度と先天異常に関する検討．糖尿病と妊娠．2010;10（1）:104-108.
日本糖尿病学会：Q17-4糖尿病患者の妊娠前管理をどのように行うか？．糖尿病診療ガイドライン2019．南江堂、2019；p288-291.
日本産科婦人科学会, 日本産婦人科医会：CQ104-3添付文書上いわゆる禁忌の医薬品のうち、妊娠初期のみに使用された場合、臨床的に有意な胎児への影響はないと判断してよい医薬品は？．産婦人科診療ガイドライン産科編2023．日本産科婦人科学会事務局、2023：p72-74.
Yuji Hiramatsu, Ikki Shimizu, Yasue Omori, Masao Nakabayashi, JGA (Japan Glycated Albumin) Study Group
Determination of reference intervals of glycated albumin and hemoglobin A1c in healthy pregnant Japanese women and analysis of their time courses and influencing factors during pregnancy.
Endocr J. 2012;59(2):145-51. doi: 10.1507/endocrj.k10e-410. Epub 2011 Dec 14.
Abstract/Text
Glycemic control is an important issue in gestational diabetes mellitus (GDM) and in diabetic pregnant women. We determined the reference intervals of glycated albumin (GA) and hemoglobin A1c (HbA1c) as glycemic control markers in healthy Japanese pregnant women and analyzed their time courses and factors that influence these variables during pregnancy. 676 women were screened for the present study. After the exclusion of non-pregnant and puerperal women, 574 women were studied to determine the reference intervals. HbA1c, GA, casual plasma glucose, urinary glucose, urinary protein, and body mass index (BMI) (non-pregnancy) were measured. HbA1c levels significantly decreased in the second trimester of pregnancy and increased in the third trimester, while GA levels significantly decreased towards the third trimester. Casual plasma glucose levels decreased in the first trimester and subsequently remained constant. The reference intervals of GA and HbA1c in the healthy pregnant women were 11.5-15.7% and 4.5-5.7%, respectively. GA levels were lower (p<0.01) and HbA1c levels were higher (p<0.05) in pregnant women with proteinuria. In the obese group, GA levels were lower (p<0.01) than those of the control group (18.5≤ BMI <25kg/m²), and HbA1c levels were higher (p<0.01) than those of the control group. On the basis of the results of this multicenter study, the reference intervals of GA and HbA1c in healthy Japanese pregnant women were determined. Strict glycemic control is essential to reduce perinatal complications. GA appears to be a useful marker for pregnant women, since it can be measured easily and changes rapidly and markedly.
日本産科婦人科学会, 日本産婦人科医会：CQ005-2妊娠糖尿病（GDM）, 妊娠中の明らかな糖尿病, ならびに糖尿病（DM）合併妊婦の管理・分娩は？．産婦人科診療ガイドライン産科編2023．日本産科婦人科学会事務局、2023；p23-27.
Sumeet R Singh, Fida Ahmad, Avtar Lal, Changhua Yu, Zemin Bai, Heather Bennett
Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis.
CMAJ. 2009 Feb 17;180(4):385-97. doi: 10.1503/cmaj.081041.
Abstract/Text
BACKGROUND: Although insulin analogues are commonly prescribed for the management of diabetes mellitus, there is uncertainty regarding their optimal use. We conducted meta-analyses to compare the outcomes of insulin analogues with conventional insulins in the treatment of type 1, type 2 and gestational diabetes.
METHODS: We updated 2 earlier systematic reviews of the efficacy and safety of rapid-and long-acting insulin analogues. We searched electronic databases, conference proceedings and "grey literature" up to April 2007 to identify randomized controlled trials that compared insulin analogues with conventional insulins. Study populations of interest were people with type 1 and type 2 diabetes (adult and pediatric) and women with gestational diabetes.
RESULTS: We included 68 randomized controlled trials in the analysis of rapid-acting insulin analogues and 49 in the analysis of long-acting insulin analogues. Most of the studies were of short to medium duration and of low quality. In terms of hemoglobin A1c, we found minimal differences between rapid-acting insulin analogues and regular human insulin in adults with type 1 diabetes (weighted mean difference for insulin lispro: -0.09%, 95% confidence interval [CI] -0.16% to -0.02%; for insulin aspart: -0.13%, 95% CI -0.20% to -0.07%). We observed similar outcomes among patients with type 2 diabetes (weighted mean difference for insulin lispro: -0.03%, 95% CI -0.12% to -0.06%; for insulin aspart: -0.09%, 95% CI -0.21% to 0.04%). Differences between long-acting insulin analogues and neutral protamine Hagedorn insulin in terms of hemoglobin A1c were marginal among adults with type 1 diabetes (weighted mean difference for insulin glargine: -0.11%, 95% CI -0.21% to -0.02%; for insulin detemir: -0.06%, 95% CI -0.13% to 0.02%) and among adults with type 2 diabetes (weighted mean difference for insulin glargine: -0.05%, 95% CI -0.13% to 0.04%; for insulin detemir: 0.13%, 95% CI 0.03% to 0.22%). Benefits in terms of reduced hypoglycemia were inconsistent. There were insufficient data to determine whether insulin analogues are better than conventional insulins in reducing long-term diabetes-related complications or death.
INTERPRETATION: Rapid-and long-acting insulin analogues offer little benefit relative to conventional insulins in terms of glycemic control or reduced hypoglycemia. Long-term, high-quality studies are needed to determine whether insulin analogues reduce the risk of long-term complications of diabetes.
Elisabeth R Mathiesen, Brendan Kinsley, Stephanie A Amiel, Simon Heller, David McCance, Santiago Duran, Shannon Bellaire, Anne Raben, Insulin Aspart Pregnancy Study Group
Maternal glycemic control and hypoglycemia in type 1 diabetic pregnancy: a randomized trial of insulin aspart versus human insulin in 322 pregnant women.
Diabetes Care. 2007 Apr;30(4):771-6. doi: 10.2337/dc06-1887.
Abstract/Text
OBJECTIVE: To assess the safety and efficacy of insulin aspart (IAsp) versus regular human insulin (HI) in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes.
RESEARCH DESIGN AND METHODS: Subjects (n = 322) who were pregnant or planning pregnancy were randomized to IAsp or HI as meal-time insulin in an open-label, parallel-group, multicenter study. Subjects had A1C < or =8% at confirmation of pregnancy. Insulin doses were titrated toward predefined glucose targets and A1C <6.5%. Outcomes assessed included risk of major maternal hypoglycemia, A1C, plasma glucose profiles, and maternal safety outcomes.
RESULTS: Major hypoglycemia occurred at a rate of 1.4 vs. 2.1 episodes/year exposure with IAsp and HI, respectively (relative risk 0.720 [95% CI 0.36-1.46]). Risk of major/major nocturnal hypoglycemia was 52% (RR 0.48 [0.20-1.143]; P = NS) lower with IAsp compared with HI. A1C was comparable with human insulin in second (IAsp-HI -0.04 [-0.18 to 0.11]) and third (-0.08 [-0.23 to 0.06]) trimesters. A total of 80% of subjects achieved an A1C < or =6.5%. At the end of first and third trimesters, average postprandial plasma glucose increments were significantly lower with IAsp than HI (P = 0.003 and P = 0.044, respectively), as were mean plasma glucose levels 90 min after breakfast (P = 0.044 and P = 0.001, respectively). Maternal safety profiles and pregnancy outcomes were similar between treatments.
CONCLUSIONS: IAsp is at least as safe and effective as HI when used in basal-bolus therapy with NPH insulin in pregnant women with type 1 diabetes and may potentially offer some benefits in terms of postprandial glucose control and preventing severe hypoglycemia.
Erika Pollex, Myla E Moretti, Gideon Koren, Denice S Feig
Safety of insulin glargine use in pregnancy: a systematic review and meta-analysis.
Ann Pharmacother. 2011 Jan;45(1):9-16. doi: 10.1345/aph.1P327. Epub 2011 Jan 4.
Abstract/Text
BACKGROUND: The prevalence of diabetes in women of childbearing age is increasing. As such, the number of pregnancies complicated by diabetes will inevitably increase. New insulin analogues such as the long-acting analogue insulin glargine may represent beneficial treatment options in pregnancy by ensuring that patients achieve excellent glycemic control without risk of maternal hypoglycemia.
OBJECTIVE: To determine the fetal safety of insulin glargine use in the treatment of diabetes in pregnancy compared with NPH insulin therapy.
METHODS: A systematic review and meta-analysis was performed of all original human studies that reported neonatal outcomes among women with pregestational or gestational diabetes who were managed with either insulin glargine or NPH insulin during pregnancy. A systematic literature search was conducted using MEDLINE, EMBASE, CINAHL, the Cochrane Central Register for Controlled Trials database, and Web of Science from 1980 to June 1, 2010. Outcomes included large size for gestational age, macrosomia, neonatal hypoglycemia, neonatal intensive care unit admissions, birth trauma, congenital anomalies, preterm delivery, perinatal mortality, respiratory distress, and hyperbilirubinemia. Relative risk ratios and weighted mean differences were computed with 95% confidence intervals.
RESULTS: Eight studies reporting on a total of 702 women with pregestational or gestational diabetes in pregnancy treated with either insulin glargine (n = 331) or NPH insulin (n = 371) met the inclusion criteria. There were no statistically significant differences in the occurrence of fetal outcomes studied with the use of insulin glargine compared to NPH insulin.
CONCLUSIONS: No evidence has been documented for increased adverse fetal outcomes with the use of insulin glargine in pregnancy compared to the use of NPH insulin. These results increase the choices for women requiring basal insulin therapy in pregnancy.
Elisabeth R Mathiesen, Moshe Hod, Marina Ivanisevic, Santiago Duran Garcia, Lise Brøndsted, Lois Jovanovic, Peter Damm, David R McCance, Detemir in Pregnancy Study Group
Maternal efficacy and safety outcomes in a randomized, controlled trial comparing insulin detemir with NPH insulin in 310 pregnant women with type 1 diabetes.
Diabetes Care. 2012 Oct;35(10):2012-7. doi: 10.2337/dc11-2264. Epub 2012 Jul 30.
Abstract/Text
OBJECTIVE: This randomized, controlled noninferiority trial aimed to compare the efficacy and safety of insulin detemir (IDet) versus neutral protamine Hagedorn (NPH) (both with prandial insulin aspart) in pregnant women with type 1 diabetes.
RESEARCH DESIGN AND METHODS: Patients were randomized and exposed to IDet or NPH up to 12 months before pregnancy or at 8-12 weeks gestation. The primary analysis aimed to demonstrate noninferiority of IDet to NPH with respect to A1C at 36 gestational weeks (GWs) (margin of 0.4%). The data were analyzed using linear regression, taking several baseline factors and covariates into account.
RESULTS: A total of 310 type 1 diabetic women were randomized and exposed to IDet (n = 152) or NPH (n = 158) up to 12 months before pregnancy (48%) or during pregnancy at 8-12 weeks (52%). The estimated A1C at 36 GWs was 6.27% for IDet and 6.33% for NPH in the full analysis set (FAS). IDet was declared noninferior to NPH (FAS, -0.06% [95% CI -0.21 to 0.08]; per protocol, -0.15% [-0.34 to 0.04]). Fasting plasma glucose (FPG) was significantly lower with IDet versus NPH at both 24 GWs (96.8 vs. 113.8 mg/dL, P = 0.012) and 36 GWs (85.7 vs. 97.4 mg/dL, P = 0.017). Major and minor hypoglycemia rates during pregnancy were similar between groups.
CONCLUSIONS: Treatment with IDet resulted in lower FPG and noninferior A1C in late pregnancy compared with NPH insulin. Rates of hypoglycemia were comparable.
