Skip to main content
SpringerLink
Log in

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

  • Original Article
  • Published:
Glycoconjugate Journal Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

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

References

  1. Huebschmann A.G., Regensteiner J.G., Vlassara H., Reusch J.E.: Diabetes and advanced glycoxidation end products. Diabetes Care. 29(6), 1420–1432 (2006)

    Article  CAS  PubMed  Google Scholar 

  2. Ramasamy R., Yan S.F., Schmidt A.M.: Advanced glycation endproducts: from precursors to RAGE: round and round we go. Amino Acids. 42(4), 1151–1161 (2012)

    Article  CAS  PubMed  Google Scholar 

  3. Coughlan M.T., Yap F.Y., Tong D.C., Andrikopoulos S., Gasser A., Thallas-Bonke V., Webster D.E., Miyazaki J., Kay T.W., Slattery R.M., Kaye D.M., Drew B.G., Kingwell B.A., Fourlanos S., Groop P.H., Harrison L.C., Knip M., Forbes J.M.: Advanced glycation end products are direct modulators of β-cell function. Diabetes. 60(10), 2523–2532 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Engelen L., Stehouwer C.D., Schalkwijk C.G.: Current therapeutic interventions in the glycation pathway: evidence from clinical studies. Diabetes Obes Metab. 15(8), 677–689 (2013)

    Article  CAS  PubMed  Google Scholar 

  5. Uribarri J., Cai W., Ramdas M., Goodman S., Pyzik R., Chen X., Zhu L., Striker G.E., Vlassara H.: Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care. 34(7), 1610–1616 (2011)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Harlev A., Wiznitzer A.: New insights on glucose pathophysiology in gestational diabetes and insulin resistance. Curr Diab Rep. 10(3), 242–247 (2010)

    Article  CAS  PubMed  Google Scholar 

  7. Reece E.A., Leguizamón G., Wiznitzer A.: Gestational diabetes: the need for a common ground. Lancet. 373(9677), 1789–1797 (2009)

    Article  PubMed  Google Scholar 

  8. Bellamy L., Casas J.P., Hingorani A.D., Williams D.: Type 2 diabetes mellitus after gestational diabetes: a systematic review and meta-analysis. Lancet. 373(9677), 1773–1779 (2009)

    Article  CAS  PubMed  Google Scholar 

  9. Harsem N.K., Braekke K., Torjussen T., Hanssen K., Staff A.C.: Advanced glycation end products in pregnancies complicated with diabetes mellitus or preeclampsia. Hypertens Pregnancy. 27(4), 374–386 (2008)

    Article  CAS  PubMed  Google Scholar 

  10. Guosheng L., Hongmei S., Chuan N., Haiying L., Xiaopeng Z., Xianqiong L.: The relationship of serum AGE levels in diabetic mothers with adverse fetal outcome. J. Perinatol. 29(7), 483–488 (2009)

    Article  CAS  PubMed  Google Scholar 

  11. Buongiorno A.M., Morelli S., Sagratella E., Castaldo P., Di Virgilio A., Maroccia E., Ricciardi G., Sciullo E., Cardellini G., Fallucca F., Sensi M.: Levels of advanced glycosylation end-products (AGE) in sera of pregnant diabetic women: comparison between type 1, type 2 and gestational diabetes mellitus. Ann. Ist. Super. Sanita. 33(3), 375–378 (1997)

    CAS  PubMed  Google Scholar 

  12. Bartakova, V., Kollarova, R., Kuricova, K., Sebekova, K., Belobradkova, J., Kankova, K.: Serum carboxymethyl-lysine, a dominant advanced glycation end product, is increased in women with gestational diabetes mellitus. Biomed. Pap. Med. Fac. Univ. Palacky Olomouc Czech Repub. (2015).

  13. Talwar D., Davidson H., Cooney J., St J.R.D.: Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay. Clin. Chem. 46(5), 704–710 (2000)

    CAS  PubMed  Google Scholar 

  14. Lynch P.L., Young I.S.: Determination of thiamine by high-performance liquid chromatography. J Chromatogr A. 881(1–2), 267–284 (2000)

    Article  CAS  PubMed  Google Scholar 

  15. Rabbani N., Thornalley P.J.: Emerging role of thiamine therapy for prevention and treatment of early-stage diabetic nephropathy. Diabetes Obes Metab. 13(7), 577–583 (2011)

    Article  CAS  PubMed  Google Scholar 

  16. Thornalley P.J., Babaei-Jadidi R., Al Ali H., Rabbani N., Antonysunil A., Larkin J., Ahmed A., Rayman G., Bodmer C.W.: High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease. Diabetologia. 50(10), 2164–2170 (2007)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Babaei-Jadidi R., Karachalias N., Ahmed N., Battah S., Thornalley P.J.: Prevention of incipient diabetic nephropathy by high-dose thiamine and benfotiamine. Diabetes. 52(8), 2110–2120 (2003)

    Article  CAS  PubMed  Google Scholar 

  18. Pacal L., Kuricova K., Kankova K.: Evidence for altered thiamine metabolism in diabetes: is there a potential to oppose gluco- and lipotoxicity by rational supplementation? World J Diabetes. 5(3), 288–295 (2014)

    Article  PubMed  PubMed Central  Google Scholar 

  19. Labay V., Raz T., Baron D., Mandel H., Williams H., Barrett T., Szargel R., McDonald L., Shalata A., Nosaka K., Gregory S., Cohen N.: Mutations in SLC19A2 cause thiamine-responsive megaloblastic anaemia associated with diabetes mellitus and deafness. Nat. Genet. 22(3), 300–304 (1999)

    Article  CAS  PubMed  Google Scholar 

  20. Zeng W.Q., Al-Yamani E., Acierno Jr. J.S., Slaugenhaupt S., Gillis T., MacDonald M.E., Ozand P.T., Gusella J.F.: Biotin-responsive basal ganglia disease maps to 2q36.3 and is due to mutations in SLC19A3. Am. J. Hum. Genet. 77(1), 16–26 (2005)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Fradin D., Bougneres P.: Three common intronic variants in the maternal and fetal thiamine pyrophosphokinase gene (TPK1) are associated with birth weight. Ann. Hum. Genet. 71(Pt 5), 578–585 (2007)

    Article  CAS  PubMed  Google Scholar 

  22. Butterworth R.F.: Maternal thiamine deficiency. A factor in intrauterine growth retardation. Ann N Y Acad Sci. 678, 325–329 (1993)

    Article  CAS  PubMed  Google Scholar 

  23. Baker H., Frank O., Thomson A.D., Langer A., Munves E.D., De Angelis B., Kaminetzky H.A.: Vitamin profile of 174 mothers and newborns at parturition. Am. J. Clin. Nutr. 28(1), 59–65 (1975)

    CAS  PubMed  Google Scholar 

  24. Losa R., Sierra M.I., Fernández A., Blanco D., Buesa J.M.: Determination of thiamine and its phosphorylated forms in human plasma, erythrocytes and urine by HPLC and fluorescence detection: a preliminary study on cancer patients. J. Pharm. Biomed. Anal. 37(5), 1025–1029 (2005)

    Article  CAS  PubMed  Google Scholar 

  25. Brunnekreeft J.W., Eidhof H., Gerrits J.: Optimized determination of thiochrome derivatives of thiamine and thiamine phosphates in whole blood by reversed-phase liquid chromatography with precolumn derivatization. J. Chromatogr. 491(1), 89–96 (1989)

    Article  CAS  PubMed  Google Scholar 

  26. Pacal L., Tomandl J., Svojanovsky J., Krusova D., Stepankova S., Rehorova J., Olsovsky J., Belobradkova J., Tanhauserova V., Tomandlova M., Muzik J., Kankova K.: Role of thiamine status and genetic variability in transketolase and other pentose phosphate cycle enzymes in the progression of diabetic nephropathy. Nephrol. Dial. Transplant. 26(4), 1229–1236 (2011)

    Article  CAS  PubMed  Google Scholar 

  27. Heller S., Salkeld R.M., Korner W.F.: Vitamin B1 status in pregnancy. Am. J. Clin. Nutr. 27(11), 1221–1224 (1974)

    CAS  PubMed  Google Scholar 

  28. Baker H., DeAngelis B., Holland B., Gittens-Williams L., Barrett Jr. T.: Vitamin profile of 563 gravidas during trimesters of pregnancy. J. Am. Coll. Nutr. 21(1), 33–37 (2002)

    Article  CAS  PubMed  Google Scholar 

  29. Ho J.E., Larson M.G., Vasan R.S., Ghorbani A., Cheng S., Rhee E.P., Florez J.C., Clish C.B., Gerszten R.E., Wang T.J.: Metabolite profiles during oral glucose challenge. Diabetes. 62(8), 2689–2698 (2013)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

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

Author information

Authors and Affiliations

  1. Department of Pathophysiology, Faculty of Medicine, Masaryk University Brno, UKB Kamenice 5/A18, 625 00, Brno, Czech Republic

    Vendula Bartáková, Anna Pleskačová, Katarína Kuricová, Lukáš Pácal, Veronika Dvořáková & Kateřina Kaňková

  2. Department of Biochemistry, Faculty of Medicine, Masaryk University Brno, Kamenice 5, 625 00, Brno, Czech Republic

    Anna Pleskačová, Marie Tomandlová & Josef Tomandl

  3. Diabetes Centre, Department of Internal Medicine – Gastroenterology, University Hospital Brno, Jihlavská 20, 625 00, Brno, Czech Republic

    Jana Bělobrádková

Authors
  1. Vendula Bartáková
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anna Pleskačová
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Katarína Kuricová
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lukáš Pácal
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Veronika Dvořáková
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jana Bělobrádková
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Marie Tomandlová
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Josef Tomandl
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Kateřina Kaňková
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kateřina Kaňková.

Ethics declarations

Conflict of interest

The authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

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

Keywords

Search

Navigation