Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes.
While the pathogenic role of dicarbonyl stress and accelerated formation of advanced glycation end products (AGEs) to glucose intolerance and to the development of diabetic complications is well established, little is known about these processes in gestational diabetes mellitus (GDM), a condition pathogenically quite similar to type 2 diabetes. The aims of the present study were (i) to determine plasma thiamine and erythrocyte thiamine diphosphate (TDP) and transketolase (TKT) activity in pregnant women with and without GDM, (ii) to assess relationships between thiamine metabolism parameters and selected clinical, biochemical and anthropometric characteristics and, finally, (iii) to analyse relationship between variability in the genes involved in the regulation of transmembrane thiamine transport (i.e. SLC19A2 and SLC19A3) and relevant parameters of thiamine metabolism. We found significantly lower plasma BMI adjusted thiamine in women with GDM (P = 0.002, Mann-Whitney) while levels of erythrocyte TDP (an active TKT cofactor) in mid-trimester were significantly higher in GDM compared to controls (P = 0.04, Mann-Whitney). However, mid-gestational TKT activity - reflecting pentose phosphate pathway activity - did not differ between the two groups (P > 0.05, Mann-Whitney). Furthermore, we ascertained significant associations of postpartum TKT activity with SNPs SLC19A2 rs6656822 and SLC19A3 rs7567984 (P = 0.03 and P = 0.007, resp., Kruskal-Wallis). Our findings of increased thiamine delivery to the cells without concomitant increase of TKT activity in women with GDM therefore indicate possible pathogenic role of thiamine mishandling in GDM. Further studies are needed to determine its contribution to maternal and/or neonatal morbidity.
Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, UKB Kamenice 5/A18, 625 00, Brno, Czech Republic.
Vendula
V
Bartáková
Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, UKB Kamenice 5/A18, 625 00, Brno, Czech Republic.|Department of Biochemistry, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00, Brno, Czech Republic.
Anna
A
Pleskačová
Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, UKB Kamenice 5/A18, 625 00, Brno, Czech Republic.
Katarína
K
Kuricová
Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, UKB Kamenice 5/A18, 625 00, Brno, Czech Republic.
Lukáš
L
Pácal
Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, UKB Kamenice 5/A18, 625 00, Brno, Czech Republic.
Veronika
V
Dvořáková
Diabetes Centre, Department of Internal Medicine - Gastroenterology, University Hospital Brno, Jihlavská 20, 625 00, Brno, Czech Republic.
Jana
J
Bělobrádková
Department of Biochemistry, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00, Brno, Czech Republic.
Marie
M
Tomandlová
Department of Biochemistry, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00, Brno, Czech Republic.
Josef
J
Tomandl
Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, UKB Kamenice 5/A18, 625 00, Brno, Czech Republic. kankov@med.muni.cz.
Kateřina
K
Kaňková
D000328:Adult; D016640:Diabetes, Gestational / Q000097:blood*; D004912:Erythrocytes / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000097:blood*; D006801:Humans; D026901:Membrane Transport Proteins / Q000097:blood; D011247:Pregnancy; D013835:Thiamine Pyrophosphate / Q000097:blood*; D014174:Transketolase / Q000097:blood*
D017127:Glycation End Products, Advanced; D026901:Membrane Transport Proteins; C120043:SLC19A2 protein, human; C492291:SLC19A3 protein, human; D014174:Transketolase; D013835:Thiamine Pyrophosphate
Advanced glycation end products; Gestational diabetes mellitus; Oral glucose tolerance test; Pregnancy; Thiamine