Oral thiamine (Vitamin B1) supplementation in subjects with type 2 diabetes mellitus:a randomised, double-blind, placebo-controlled crossover trial assessing biophysical markers of endothelial function, oxidant stress, insulin sensitivity and vascular inflammation

摘要

Background and Aims Type 2 diabetes is increasing in prevalence and is associated with a threefold increased risk of cardiovascular mortality despite management of the traditional risk factors. Novel risk factors have been hypothesised that contribute to the pathogenesis of both type 2 diabetes and atherosclerosis and include oxidative stress, inflammation and endothelial dysfunction. Thiamine has been shown to be an important cofactor in the attenuation of these novel risk factors and people with type 2 diabetes have been shown to be thiamine deficient. This study tested the hypothesis that thiamine supplementation may improve endothelial function, oxidative stress, vascular inflammation and insulin resistance in subjects with type 2 diabetes who have a high cardiovascular risk profile. Methods Subjects with type 2 diabetes underwent a randomised, double blind, placebo-­‐controlled crossover pilot study receiving 300mg daily of oral thiamine hydrochloride or placebo for eight weeks with a two week washout period. Measurements were taken for endothelial function (change in the reflective index post salbutamol using digital photoplethysmography, plasma cyclic GMP, plasma sVCAM-­‐1, urinary albumin: creatinine ratio), insulin resistance (HOMA-­‐IR), oxidative stress (glutathione ratio, CuPRAC-­BCS) and inflammation (hsCRP) at the beginning and end of treatment with both thiamine and placebo. Results 34 patients (20 male) completed the study. Mean age 61 ± 9.4 years, HbA1c 7.46 ± 0.88%, blood pressure 137/77 ± 18/9 mmHg, total cholesterol 4.01 ± 1.11 mmol/l, HDL cholesterol 1.00 ± 0.30 mmol/l, triglycerides 1.87 ± 1.39 3 mmol/l. The majority of the patients were on two or more glucose lowering therapies with 88% on metformin. Most of the patients were on other cardiovascular disease modifying medications (statins or antihypertensive agents). Treatment with thiamine demonstrated a significant increase in thiamine diphosphate levels (310 ± 82 nmol/l post thiamine vs. 178 ± 32 nmol/l post placebo, p=0.001) but no significant difference in markers of endothelial function, insulin resistance, oxidative stress or inflammation or other metabolic markers. Conclusion In this cohort of patients treatment with 300mg per day of oral thiamine for eight weeks in well-­‐controlled type 2 diabetes at high cardiovascular risk, demonstrated no significant improvement in endothelial function, insulin resistance, oxidative stress or inflammation.