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Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes

Abstract

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.

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Abbreviations

AGEs:

advanced glycation end products

BMI:

body mass index

FPG:

fasting plasma glucose

GDM:

gestational diabetes mellitus

HPLC:

high-performance liquid chromatography

oGTT:

oral glucose tolerance test

PPP:

pentose phosphate pathway

SLC19A2:

solute carrier family 19 member 2

SLC19A3:

solute carrier family 19 member 3

SNP:

single nucleotide polymorphism

TDP:

thiamine diphosphate

THTR1:

thiamine transporter 1

THTR2:

thiamine transporter 2

TKT:

transketolase

TPK1:

thiamine pyrophosphokinase

T2DM:

type 2 diabetes mellitus

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Acknowledgments

Study was supported by the grant NT13198 from The Ministry of Health of Czech Republic.

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Correspondence to Kateřina Kaňková.

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Bartáková, V., Pleskačová, A., Kuricová, K. et al. Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes. Glycoconj J 33, 591–598 (2016). https://doi.org/10.1007/s10719-016-9688-9

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  • DOI: https://doi.org/10.1007/s10719-016-9688-9

Keywords

  • Advanced glycation end products
  • Gestational diabetes mellitus
  • Thiamine
  • Pregnancy
  • Oral glucose tolerance test