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

2020 ◽  
Vol 15 ◽  
Author(s):  
Claudio Daniel Gonzalez ◽  
Victoria Insussarry Perkins ◽  
Agustina Alves de Lima ◽  
Rocio Fogar ◽  
Gustavo D. Frechtel ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Neonatal Diabetes ◽  
Pharmacokinetic Profile ◽  
Narrative Review ◽  
Maturity Onset Diabetes ◽  
First Semester ◽  
Onset Diabetes ◽  
Highly Sensitive ◽  
Expression Activity ◽  
The Impact

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.

scholarly journals Maturity Onset Diabetes of the Young due to Glucokinase, HNF1-A, HNF1-B, and HNF4-A Mutations in a Cohort of Turkish Children Diagnosed as Type 1 Diabetes Mellitus

2018 ◽  
Vol 90 (4) ◽  
pp. 257-265 ◽  
Author(s):  
Elif Ozsu ◽  
Filiz Mine Cizmecioglu ◽  
Gul Yesiltepe Mutlu ◽  
Aysegul Bute Yuksel ◽  
Mursel Calıskan ◽  
...  
Keyword(s):  
Type 1 Diabetes ◽  
Rare Condition ◽  
High Sensitivity ◽  
Genetic Mutation ◽  
Nuclear Factor ◽  
Maturity Onset Diabetes ◽  
Hepatocyte Nuclear Factor ◽  
Turkish Children ◽  
Onset Diabetes

Background/Aims: Maturity onset diabetes of the young (MODY) is a rare condition often misdiagnosed as type 1 diabetes (T1D). The purposes of this study were: to identify any patients followed in a large Turkish cohort as T1D, with an atypical natural history, who may in fact have MODY, and to define the criteria which would indicate patients with likely MODY as early as possible after presentation to allow prompt genetic testing. Methods: Urinary C-peptide/creatinine ratio (UCPCR) was studied in 152 patients having a diagnosis of T1D for at least 3 years. Those with a UCPCR ≥0.2 nmol/mmol were selected for genetic analysis of the Glucokinase (GCK), Hepatocyte nuclear factor 1a (HNF1A), Hepatocyte nuclear factor 4a (HNF4A), and Hepatocyte nuclear factor 1b (HNF1B) genes. This UCPCR cut-off was used because of the reported high sensitivity and specificity. Cases were also evaluated using a MODY probability calculator. Results: Twenty-three patients from 152 participants (15.1%) had a UCPCR indicating persistent insulin reserve. The mean age ± SD of the patients was 13.6 ± 3.6 years (range 8.30–21.6). Of these 23, two (8.7%) were found to have a mutation, one with HNF4A and one with HNF1B mutation. No mutations were detected in the GCK or HNF1A genes. Conclusion: In Turkish children with a diagnosis of T1D but who have persistent insulin reserve 3 years after diagnosis, up to 9% may have a genetic mutation indicating a diagnosis of MODY.

scholarly journals Low serum level of high-sensitivity C-reactive protein in a Japanese patient with maturity-onset diabetes of the young type 3 (MODY3)

2014 ◽  
Vol 5 (5) ◽  
pp. 513-516 ◽  
Author(s):  
Tsuyoshi Ohki ◽  
Yoshihiko Utsu ◽  
Shinya Morita ◽  
Md. Fazlul Karim ◽  
Yoshifumi Sato ◽  
...  
Keyword(s):  
Serum Level ◽  
Japanese Patient ◽  
High Sensitivity ◽  
Maturity Onset Diabetes ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Onset Diabetes ◽  
Type 3 ◽  
Low Serum

scholarly journals Assessment of High-Sensitivity C-Reactive Protein Levels as Diagnostic Discriminator of Maturity-Onset Diabetes of the Young Due to HNF1A Mutations

Diabetes Care ◽  
2010 ◽  
Vol 33 (9) ◽  
pp. 1919-1924 ◽  
Author(s):  
K. R. Owen ◽  
G. Thanabalasingham ◽  
T. J. James ◽  
F. Karpe ◽  
A. J. Farmer ◽  
...  
Keyword(s):  
High Sensitivity ◽  
Maturity Onset Diabetes ◽  
C Reactive Protein ◽  
Protein Levels ◽  
Reactive Protein ◽  
Onset Diabetes

Monogenic Diabetes Mellitus: Neonatal Diabetes and Maturity-Onset Diabetes of the Young

2021 ◽  
pp. 279-298
Author(s):  
Siri Atma W. Greeley ◽  
Mary K. McCauley ◽  
Louis H. Philipson ◽  
Mark A. Sperling
Keyword(s):  
Diabetes Mellitus ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes

scholarly journals Evolution- and Structure-Based Computational Strategy Reveals the Impact of Deleterious Missense Mutations on MODY 2 (Maturity-Onset Diabetes of the Young, Type 2)

Theranostics ◽  
2014 ◽  
Vol 4 (4) ◽  
pp. 366-385 ◽  
Author(s):  
Doss C. Priya George ◽  
Chiranjib Chakraborty ◽  
SA Syed Haneef ◽  
Nagarajan NagaSundaram ◽  
Luonan Chen ◽  
...  
Keyword(s):  
Missense Mutations ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
The Impact ◽  
Computational Strategy

scholarly journals MOLECULAR GENETICS AND CLINICAL ASPECTS OF MONOGENIC DIABETES MELLITUS

2012 ◽  
Vol 67 (1) ◽  
pp. 81-86 ◽  
Author(s):  
V. A. Peterkova ◽  
T. L. Kuraeva ◽  
S. A. Prokof’ev ◽  
A. O. Emel'yanov ◽  
E. Yu. Zakharova ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Genetics ◽  
Neonatal Diabetes ◽  
Clinical Results ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Clinical Aspects ◽  
Maturity Onset Diabetes ◽  
Onset Diabetes ◽  
Didmoad Syndrome

The paper is dedicated to clinical and laboratory aspects of Diabetes Mellitus non-immune forms, such as neonatal Diabetes Mellitus, Maturity Onset Diabetes of young (MODY), DIDMOAD-syndrome, Wolframe syndrome, Alstrom syndrome and its determinating genes. The analysis of proper clinical results are present in this paper.

scholarly journals Human iPSCs-Derived Endothelial Cells with Mutation in HNF1A as a Model of Maturity-Onset Diabetes of the Young

Cells ◽  
2019 ◽  
Vol 8 (11) ◽  
pp. 1440 ◽  
Author(s):  
Kachamakova-Trojanowska ◽  
Stepniewski ◽  
Dulak
Keyword(s):  
Endothelial Cells ◽  
Microvascular Complications ◽  
Maturity Onset Diabetes ◽  
Isogenic Lines ◽  
Onset Diabetes ◽  
Human Ipscs ◽  
Induced Pluripotent ◽  
Biallelic Mutations ◽  
Human Ipsc ◽  
The Impact

Patients with HNF1A-maturity-onset diabetes of the young (MODY) often develop endothelial dysfunction and related microvascular complications, like retinopathy. As the clinical phenotype of HNF1A-MODY diabetes varies considerably, we used human induced pluripotent stem cells (hiPSCs) from two healthy individuals (control) to generate isogenic lines with mutation in HNF1A gene. Subsequently, control hiPSCs and their respective HNF1A clones were differentiated toward endothelial cells (hiPSC-ECs) and different markers/functions were compared. Human iPSC-ECs from all cell lines showed similar expression of CD31 and Tie-2. VE-cadherin expression was lower in HNF1A-mutated isogenic lines, but only in clones derived from one control hiPSCs. In the other isogenic set and cells derived from HNF1A-MODY patients, no difference in VE-cadherin expression was observed, suggesting the impact of the genetic background on this endothelial marker. All tested hiPSC-ECs showed an expected angiogenic response regardless of the mutation introduced. Isogenic hiPSC-ECs responded similarly to stimulation with pro-inflammatory cytokine TNF- with the increase in ICAM-1 and permeability, however, HNF1A mutated hiPSC-ECs showed higher permeability in comparison to the control cells. Summarizing, both mono- and biallelic mutations of HNF1A in hiPSC-ECs lead to increased permeability in response to TNF- in normal glycemic conditions, which may have relevance to HNF1A-MODY microvascular complications.

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