High prevalence of low plasma thiamine concentration in diabetes linked to a marker of vascular disease

Abstract

Aims/hypothesis To assess thiamine status by analysis of plasma, erythrocytes and urine in type 1 and type 2 diabetic patients and links to markers of vascular dysfunction. Methods Diabetic patients (26 type 1 and 48 type 2) with and without microalbuminuria and 20 normal healthy control volunteers were recruited. Erythrocyte activity of transketolase, the concentrations of thiamine and related phosphorylated metabolites in plasma, erythrocytes and urine, and markers of metabolic control and vascular dysfunction were determined. Results Plasma thiamine concentration was decreased 76% in type 1 diabetic patients and 75% in type 2 diabetic patients: normal volunteers 64.1 (95% CI 58.5-69.7) nmol/l, type 1 diabetes 15.3 (95% CI 11.5-19.1) nmol/l, p< 0.001, and type 2 diabetes 16.3 (95% CI 13.0-9.6) nmol/l, p<0.001. Renal clearance of thiamine was increased 24-fold in type 1 diabetic patients and 16-fold in type 2 diabetic patients. Plasma thiamine concentration correlated negatively with renal clearance of thiamine (r=−0.531, p< 0.001) and fractional excretion of thiamine (r=−0.616, p< 0.001). Erythrocyte transketolase activity correlated negatively with urinary albumin excretion (r=−0.232, p<0.05). Thiamine transporter protein contents of erythrocyte membranes of type 1 and type 2 diabetic patients were increased. Plasma thiamine concentration and urinary excretion of thiamine correlated negatively with soluble vascular adhesion molecule-1 (r=−0.246, p<0.05, and −0.311, p<0.01, respectively). Conclusions/interpretation Low plasma thiamine concentration is prevalent in patients with type 1 and type 2 diabetes, associated with increased thiamine clearance. The conventional assessment of thiamine status was masked by increased thiamine transporter content of erythrocytes.

The uremic toxin oxythiamine causes functional thiamine deficiency in end-stage renal disease by inhibiting transketolase activity

“…14 respectively. 51 Oxythiamine is not detectable by the thiochrome assay as it lacks the 4-aminopyrimidinyl moiety required for thiochrome formation.…”

“…Recent studies in diabetes and CKD suggest there are also abnormalities of thiamine transport due to tissue-specific down regulation of thiamine transporters. 14,37,47 Measurement of renal clearance of thiamine is a sensitive clinical marker of this. 14 Red blood cell transketolase activity is valuable to assess impact on the pentosephosphate pathway and αETKA to explore cause of transketolase activity deficit.…”

Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

“…Interestingly, increased clearance was prevented by high-dose thiamine supplementation [26] . Thiamine renal clearance is also increased in subjects with T1DM (by 24-fold) and T2DM (by 16-fold) [24] . Further changes of thiamine metabolism probably occur with the development of chronic diabetic microvascular complications namely diabetic nephropathy together with chronic kidney disease (CKD).…”

“…Patients with type 1 and 2 diabetes mellitus (T1DM and T2DM) do not have a marked thiamine deficiency [conventionally defined as an increase of TKT activity in red blood cells (RBC) higher than 15% after addition of saturating amount of TDP]. However, plasma thiamine levels in diabetics are decreased by 75% compared to healthy subjects [24] . RFC-1 and THTR1 protein expression in RBCs obtained from diabetic patients (both T1DM and T2DM) is higher than in healthy subjects [24] .…”

Efficient Transdermal Delivery of Benfotiamine in an Animal Model

“…However, a number of studies found an altered thiamine handling in the kidneys of diabetic patients [16][17][18]. Benfotiamine, (S-benzoylthiamine-Omonophosphate), a derivative of the vitamin B1 or thiamine, has a much higher bioavailability than thiamine and, as a result, accumulates in the target tissues much more than thiamine itself [15,19,20].…”