Background: Oxidative stress has been implicated in the development and progression of complications in type 1 diabetes (T1DM). Vitamin E (α-tocopherol) undergoes β-oxidation of its chomanol ring and the resulting metabolite α-TLHQ has been proposed as a potential biomarker of oxidative stress. HbA1c relates in T1DM to microvascular complications predominantly although the end-points are late in disease development. The oxidative stress process may act independently of HbA1c and oxidative stress markers may be useful predictors of early vascular damage.
Objective and hypotheses: We aimed to measure the levels of vitamin E metabolites in T1DM and see whether they were elevated when compared with age-matched controls and to relate the measures to HbA1c, mode of insulin therapy and duration of diabetes.
Method: We developed a new assay using triple quadrupole tandem mass spectrometry to measure vitamin E metabolites α-TLHQ-SO3 and α-TLHQ-glucuronide. Urine samples were analysed from 133 children with T1DM and 88 age-matched controls. All subjects had normal renal function.
Results: Both vitamin E metabolites were significantly higher in T1DM compared to controls: mean α-TLHQ-SO3 (nmol/mmol creatinine) 3.09±0.39 T1DM vs 1.96±0.33 controls (P=0.04); mean α-TLHQ-glucuronide (nmol/mmol creatinine) 76.63±5.65 T1DM vs 47.87±2.16 controls (P<0.0001). No statistically significant differences were seen with HbA1c level, mode of insulin therapy, duration of diabetes or use of continuous glucose monitors.
Conclusion: These results demonstrate that urinary α-TLHQ, a biomarker of oxidative stress, is elevated in T1DM. Further work is required to validate these results and analyse variation with other parameters of diabetic control.