Pregnancy Complicated by the Most Frequent forms of Maturity Onset Diabetes of the Young: a Narrative Review on its Pharmacological Implications

GONZALEZ, CLAUDIO DANIEL; FOGAR, ROCIO; DE LIMA, AGUSTINA ALVES; DI GIROLAMO, GUILLERMO; PERKINS, VICTORIA INSUSSARRY; FRECHTEL, GUSTAVO D.

Current Clinical Pharmacology

Betham Science

Año: 2020 vol. 15

1574-8847

Background: Monogenic diabetes (MFD) represents close to 2% of all the cases of diabetes diagnosed in people aged ≤45. Maturity-onset diabetes of the young (MODY), neonatal diabetes and several syndromic forms of diabetes are included among the most characteristic MDF. MODY is the most frequent type of MFD being MODY 1, 2, 3 and 5 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.Methods: A comprehensive literature search was carried out to identify eligible studies from MEDLINE/PubMed, EMBASE and SCIELO databases through 1970 first semester.Results: 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 in 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 active drug.Conclusion: The impact of changes on the pharmacological behavior of drugs like SU and other metabolized/transported by mechanisms altered in pregnancy complicated by MODY is unknown. However, a 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.