Gonzalez Claudio Daniel, Perkins Victoria Insussarry, de Lima Agustina Alves, Fogar Rocio, Frechtel Gustavo D, Di Girolamo Guillermo
Universidad de Buenos Aires, Facultad de Medicina, Centro de Vigilancia y Seguridad de Medicamentos, Buenos Aires, Argentina.
Departamento de Farmacología, Escuela de Medicina, Instituto Universitario CEMIC, Buenos Aires, Argentina.
Curr Rev Clin Exp Pharmacol. 2021;16(3):228-234. doi: 10.2174/1574884715666200910160007.
Monogenic Diabetes (MFD) represents close to 2% of all the cases of diabetes diagnosed in people younger than 45 years old. Maturity-Onset Diabetes of the Young (MODY), neonatal diabetes, and several syndromic forms of diabetes are included among the most accounts for about typical forms of MDF. MODY is the most frequent type of MFD, with MODY 1, 2, 3, and 5 being the most prevalent forms. The aim of this narrative review is to describe pregnancy associated changes in the pharmacological profile of the antidiabetic drugs used in women with the most frequent MODY subtypes.
A comprehensive literature search was carried out to identify eligible studies from MEDLINE/ PubMed, EMBASE, and SCIELO databases from 1970 to 2019 first semester.
Pregnancy introduces changes in the pharmacodynamic and pharmacokinetic profile of some of the treatments used in MODY. MODY 3 (also known as HNF1-A MODY) is the most frequent MDF. MODY 3 patients are highly sensitive to Sulfonylureas (SU). This is also the case for MODY pregnant women. This high sensitivity to SU is also registered in patients with MODY 1 (HNF4-A MODY). Pharmacodynamic changes have been proposed to explain this behavior (Epac2 hyperactivity). However, changes in expression/activity of the metabolizing CYP2C9 cytochrome and/or alterations in the drug transporters oatp1 (Slc21a1), Lst-1 (Slc21a6), OATPD (SLC21A11), and oat2 may better explain, at least in part, this phenomenon by an increase in the concentration of the active drug.
The impact of changes in the pharmacological behavior of drugs like SU and other metabolized/transported by mechanisms altered in a pregnancy complicated by MODY is unknown. However, switching-to-insulin recommendation formulated for MODY 1 and 3 seems to be justified. Further research in this field is needed for a better understanding of changes in drug activity associated with this particular subset of patients with MFD.
单基因糖尿病（MFD）约占45岁以下人群确诊糖尿病病例的2%。青年发病的成年型糖尿病（MODY）、新生儿糖尿病以及几种综合征性糖尿病形式是MDF的典型形式。MODY是最常见的MFD类型，其中MODY 1、2、3和5最为普遍。本叙述性综述的目的是描述患有最常见MODY亚型的女性使用的抗糖尿病药物在妊娠期间药理学特征的相关变化。
进行了全面的文献检索，以从1970年至2019年上半年的MEDLINE/ PubMed、EMBASE和SCIELO数据库中识别符合条件的研究。
妊娠会使MODY患者使用的某些治疗药物的药效学和药代动力学特征发生变化。MODY 3（也称为HNF1 - A MODY）是最常见的MDF。MODY 3患者对磺脲类药物（SU）高度敏感。MODY孕妇也是如此。MODY 1（HNF4 - A MODY）患者也表现出对SU的这种高敏感性。有人提出药效学变化来解释这种行为（Epac2活性过高）。然而，代谢性细胞色素CYP2C9的表达/活性变化和/或药物转运体oatp1（Slc21a1）、Lst - 1（Slc21a6）、OATPD（SLC21A11）和oat2的改变可能至少部分地通过活性药物浓度的增加更好地解释这一现象。
在合并MODY的妊娠中，像SU等药物以及其他通过机制改变而代谢/转运的药物的药理学行为变化的影响尚不清楚。然而，针对MODY 1和3提出的改用胰岛素的建议似乎是合理的。需要在该领域进行进一步研究，以更好地了解与这一特定MFD患者亚组相关的药物活性变化。
