High‐Dose Thiamine Therapy Counters Dyslipidemia and Advanced Glycation of Plasma Protein in Streptozotocin‐Induced Diabetic Rats

Abstract

The streptozotocin-induced (STZ) diabetic rat experimental model of diabetes on insulin maintenance therapy exhibits dyslipidemia, mild thiamine deficiency, and increased plasma protein advanced glycation end products (AGEs). The reversal of thiamine deficiency by high-dose thiamine and S-benzoylthiamine monophosphate (benfotiamine) prevented the development of incipient nephropathy. Recently, we reported that high-dose thiamine (but not benfotiamine) countered diabetic dyslipidemia. To understand further the differences between the effects of thiamine and benfotiamine therapy, we quantified the levels of the AGEs in plasma protein. We found hydroimidazolone AGE residues derived from glyoxal and methylglyoxal, G-H1 and MG-H1, were increased 115% and 68% in STZ diabetic rats, with respect to normal controls, and were normalized by both thiamine and benfotiamine; whereas N-carboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL) residues were increased 74% and 118% in STZ diabetic rats and were normalized by thiamine only. The lack of effect of benfotiamine on plasma CML and CEL residue concentrations suggests there may be important precursors of plasma protein CML and CEL residues other than glyoxal and methylglyoxal. These are probably lipid-derived aldehydes.

Benfotiamine Prevents Macro- and Microvascular Endothelial Dysfunction and Oxidative Stress Following a Meal Rich in Advanced Glycation End Products in Individuals With Type 2 Diabetes

“…A study by Beisswenger et al (23), conducted in people with diabetes, showed that hyperglycemia rapidly induces in vivo synthesis of dicarbonyls, which are highly reactive AGE precursors such as MG and 3-deoxyglucosone. Benfotiamine decreased dicarbonyls formation in animal models (41). In our study, the postprandial circulating MG levels increased maximally at 4 h, an effect prevented by benfotiamine.…”

Degradation products of proteins damaged by glycation, oxidation and nitration in clinical type 1 diabetes

“…CML residue concentrations in plasma protein and haemoglobin were also linked to 3DG-H residue concentrations and to pentosidine residue concentration in haemoglobin. CML and CEL residues in plasma protein may be formed from lipid-derived precursors without apparent mediation by glyoxal and methylglyoxal [36].…”

The Role of Thiamine in Autism

“…Thiamine and a benfotiamine supplement prevented tissue accumulation and increased the urinary excretion of protein glycation, oxidation and nitration adducts associated with experimental diabetes [175]. Karachalias et al [176] reported that the hydroimidazolone of AGE residues derived from glyoxal and methylglyoxal (G-H1 and MG-H1, respectively) increased by 115% and 68%, respectively, in streptozotocin-induced diabetic rats, and thiamine and benfotiamine normalized these residues. However, Ncarboxymethyl-lysine (CML) and N-carboxyethyl-lysine (CEL) residues increased by 74% and 118%, respectively, in diabetic-induced rats, and only thiamine normalized these residues.…”