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

P J Thornalley, R Babaei-Jadidi, H Al Ali, N Rabbani, A Antonysunil, J Larkin, A Ahmed, G Rayman, C W Bodmer, P J Thornalley, R Babaei-Jadidi, H Al Ali, N Rabbani, A Antonysunil, J Larkin, A Ahmed, G Rayman, C W Bodmer

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.

Figures

Fig. 1
Fig. 1
Thiamine status of diabetic patients and link to sVCAM-1. a Frequency ribbon graph of plasma thiamine concentration. b Inverse relationship between plasma thiamine concentration and thiamine clearance. Nonlinear regression equation: [Thiamine]Plasma = 47.7 × ClThiamine−0.274, p<0.001. c Inverse relationship between plasma thiamine concentration and FEThiamine. Nonlinear regression equation: [Thiamine]Plasma = 74.0 × FEThiamine−0.448, p<0.001
Fig. 2
Fig. 2
a Schematic diagram of thiamine membrane transport and metabolism in erythrocytes. b Representative Western blot of THTR-1, RFC-1 and housekeeping protein β-actin of erythrocyte membranes. Lanes 1–3, normal volunteers; lanes 4–6, type 1 diabetic patients; and lanes 7–9, type 2 diabetic patients. T, Thiamine
Fig. 3
Fig. 3
Correlation of sVCAM-1 with plasma thiamine concentration (a) and urinary thiamine excretion (b). Solid horizontal line, reference mean of sVCAM-1 of normal volunteers; broken horizontal line, upper limit of sVCAM-1 of normal volunteers

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