Imbergamo Maria P, Amato Marco C, Sciortino Giovanna, Gambina Massimo, Accidenti Maria, Criscimanna Angela, Giordano Carla, Galluzzo Aldo
Section of Endocrinology, Department of Experimental Oncology and Clinical Applications (DOSAC), Faculty of Medicine, University of Palermo, Palermo, Italy.
Clin Ther. 2008 Aug;30(8):1476-84. doi: 10.1016/j.clinthera.2008.08.013.
Insulin glargine is a once-daily basal insulin analog with prolonged duration of action and absence of an evident peak. Glargine is associated with reduced frequency of hypoglycemic episodes (mostly nocturnal) as well as effective glycemic control. Maintenance of good metabolic control before conception and throughout pregnancy is essential to lower the risk of fetal malformations. Glargine might be a valuable alternative in the management of pregnancies complicated by diabetes mellitus. However, because its clinical utility has not been established, the use of glargine is not currently recommended during pregnancy.
The aim of this study was to retrospectively evaluate (years 2004-2007) the effectiveness and safety of insulin glargine compared with neutral protamine Hagedorn (NPH) in women affected by type 1 diabetes mellitus (T1DM) during pregnancy.
The study comprised pregnant women affected by T1DM who were followed up in the Diabetes and Pregnancy Outpatient Clinic at the University of Palermo, Palermo, Italy, within 8 +/- 3.4 weeks subsequent to a positive pregnancy test. All patients with T1DM were treated with conventional basal-bolus insulin therapy (aspart or lispro analogs at the 3 main meals plus glargine or NPH at bedtime). Healthy pregnant women were used as controls for fetal and neonatal parameters. Patients were consecutively enrolled. In all women, metabolic status was determined daily by mean glycemic values (2-hour postprandial blood glucose) and glycosylated hemoglobin (HbA1c) values (at 3-month intervals). Fetal measurements (<50th and >90th centiles of the head circumference, abdomen circumference, and femoral length) were evaluated by ultrasound at second and third trimesters. Weight and femoral length were assessed at birth, and neonates were classified according to the fetal growth curve for the Italian population (<10th centile = small for gestational age; and >90th centile = large for gestational age (LGA).
A total of 73 pregnant women (30 with T1DM and 43 healthy [control]) were included in the study. Of the 30 diabetic pregnant women included in the study, 15 (mean [SD] age, 27.4 [5.2] years; mean pregravidic weight, 59.7 [11.7] kg) maintained their preconception therapy with glargine, and 15 (mean age, 30.1 [2.4] years; mean pregravidic weight, 60.7 [8.7] kg) with NPH. No significant difference was observed between the glargine-treated group and the NPH-treated group with regard to pregravidic hypertension, third-trimester preeclampsia, maternal complications and/or their progression during pregnancy (diabetic retinopathy, micro- or macroalbuminuria) and episodes of mild hypoglycemia, severe hypoglycemia, and ketosis. There were no significant between group differences in insulin requirements (IU/kg of body weight) and glycemic profile, with the exception of better fasting and 2 hours after breakfast glycemic values in the glargine group during the first (P = 0.008 and P < 0.001, respectively) and the second (P = 0.015 and P = 0.016) trimesters, confirmed by the lower HbA1c levels in the first trimester (P = 0.037). The frequency of femoral length <50th centile at both second and third trimesters was 4/15 (26.7%) in the glargine-treated group (P = 0.033 and P = 0.013, respectively, vs control), 3/15 (20.0%) and 1/15 (6.7%), respectively, in the NPH-treated group (both, P = NS vs control), and 2/43 (4.7%) and 1/43 (2.3%), respectively, in the control group. The prevalence of LGA was 7/15 (46.7%) in the glargine group (P < 0.001 vs control), 4/15 (27.6%) in the NPH group (P = 0.033 vs control), and 2/43 (4.7%) in the control group.
Although our retrospective study involved only a small number of participants, no significant difference was found in glycemic control between glargine and NPH treatments. Use of glargine was associated with a significantly higher frequency of femoral length <50th centile. Further larger prospective studies are necessary to assess the safety profile of glargine in T1DM during pregnancy.
甘精胰岛素是一种每日注射一次的基础胰岛素类似物，作用持续时间延长且无明显峰值。甘精胰岛素与低血糖事件（主要是夜间低血糖）发生频率降低以及有效的血糖控制相关。在受孕前及整个孕期维持良好的代谢控制对于降低胎儿畸形风险至关重要。甘精胰岛素可能是治疗合并糖尿病的妊娠的一种有价值的替代药物。然而，由于其临床效用尚未确立，目前不建议在孕期使用甘精胰岛素。
本研究的目的是回顾性评估（2004年至2007年）在孕期1型糖尿病（T1DM）女性中，甘精胰岛素与中性鱼精蛋白锌胰岛素（NPH）相比的有效性和安全性。
本研究纳入了在意大利巴勒莫大学糖尿病与妊娠门诊随访的T1DM孕妇，这些孕妇在妊娠试验阳性后的8±3.4周内就诊。所有T1DM患者均接受常规基础-餐时胰岛素治疗（三餐主要使用门冬胰岛素或赖脯胰岛素类似物，睡前使用甘精胰岛素或NPH）。健康孕妇作为胎儿和新生儿参数的对照。患者连续入组。所有女性每天通过平均血糖值（餐后2小时血糖）和糖化血红蛋白（HbA1c）值（每3个月一次）来确定代谢状态。在孕中期和孕晚期通过超声评估胎儿测量值（头围、腹围和股骨长度低于第50百分位数和高于第90百分位数）。在出生时评估体重和股骨长度，并根据意大利人群的胎儿生长曲线对新生儿进行分类（低于第10百分位数 = 小于胎龄；高于第90百分位数 = 大于胎龄[LGA]）。
本研究共纳入73名孕妇（30名T1DM患者和43名健康[对照]）。在纳入研究的30名糖尿病孕妇中，15名（平均[标准差]年龄，27.4[5.2]岁；孕前平均体重，59.7[11.7]kg）维持孕前使用甘精胰岛素治疗，15名（平均年龄，30.1[2.4]岁；孕前平均体重，60.7[8.7]kg）维持孕前使用NPH治疗。在孕前高血压、孕晚期先兆子痫、母体并发症和/或其在孕期的进展（糖尿病视网膜病变、微量或大量蛋白尿）以及轻度低血糖、严重低血糖和酮症发作方面，甘精胰岛素治疗组和NPH治疗组之间未观察到显著差异。胰岛素需求量（IU/体重kg）和血糖谱在组间无显著差异，但甘精胰岛素组在孕早期（分别为P = 0.008和P < 0.001）和孕中期（分别为P = 0.015和P = 0.016）的空腹血糖和早餐后2小时血糖值更好，孕早期HbA1c水平较低证实了这一点（P = 0.037）。在甘精胰岛素治疗组中，孕中期和孕晚期股骨长度低于第50百分位数的频率分别为4/15（26.7%）（与对照组相比，分别为P = 0.033和P = 0.013），在NPH治疗组中分别为3/15（20.0%）和1/15（6.7%）（两者与对照组相比，P = 无显著性差异），在对照组中分别为2/43（4.7%）和1/43（2.3%）。LGA的患病率在甘精胰岛素组中为7/15（46.7%）（与对照组相比，P < 0.001），在NPH组中为4/15（27.6%）（与对照组相比，P = 0.033），在对照组中为2/43（4.7%）。
尽管我们的回顾性研究仅涉及少数参与者，但甘精胰岛素和NPH治疗在血糖控制方面未发现显著差异。使用甘精胰岛素与股骨长度低于第50百分位数的频率显著较高相关。需要进一步进行更大规模的前瞻性研究来评估甘精胰岛素在孕期T1DM中的安全性。
