Aims/hypothesis
We determined whether fixed doses of benfotiamine in combination with slow-release α-lipoic acid normalise markers of reactive
oxygen species-induced pathways of complications in humans.
Methods
Male participants with and without type 1 diabetes were studied in the General Clinical Research Centre of the Albert Einstein
College of Medicine. Glycaemic status was assessed by measuring baseline values of three different indicators of hyperglycaemia.
Intracellular AGE formation, hexosamine pathway activity and prostacyclin synthase activity were measured initially, and after
2 and 4 weeks of treatment.
Results
In the nine participants with type 1 diabetes, treatment had no effect on any of the three indicators used to assess hyperglycaemia.
However, treatment with benfotiamine plus α-lipoic acid completely normalised increased AGE formation, reduced increased monocyte
hexosamine-modified proteins by 40% and normalised the 70% decrease in prostacyclin synthase activity from 1,709 ± 586 pg/ml
6-keto-prostaglandin F1α to 4,696 ± 533 pg/ml.
Conclusions/interpretation
These results show that the previously demonstrated beneficial effects of these agents on complication-causing pathways in
rodent models of diabetic complications also occur in humans with type 1 diabetes.
Trial registration: NCT00703989
Funding: Juvenile Diabetes Research Foundation grant 8-2003-784 and GCRC grant MO1-RR12248.
Keywords Advanced glycation endproducts - Benfotiamine - Diabetic complications - Hexosamine pathway - Hyperglycaemia - Lipoic acid - Prostacyclin synthase - Reactive oxygen species - Type 1 diabetes
D. Edelstein died during the preparation of this manuscript.