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

Glycoconj J. 2016 Aug;33(4):591-8. doi: 10.1007/s10719-016-9688-9. Epub 2016 Jun 10.

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.

Keywords: Advanced glycation end products; Gestational diabetes mellitus; Oral glucose tolerance test; Pregnancy; Thiamine.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Diabetes, Gestational / blood*
  • Erythrocytes / metabolism*
  • Female
  • Follow-Up Studies
  • Glycation End Products, Advanced / blood*
  • Humans
  • Membrane Transport Proteins / blood
  • Pregnancy
  • Thiamine Pyrophosphate / blood*
  • Transketolase / blood*

Substances

  • Glycation End Products, Advanced
  • Membrane Transport Proteins
  • SLC19A2 protein, human
  • SLC19A3 protein, human
  • Transketolase
  • Thiamine Pyrophosphate