Oral benfotiamine plus alpha-lipoic acid normalises complication-causing pathways in type 1 diabetes.
OBJECTIVE
We determined whether fixed doses of benfotiamine in combination with slow-release alpha-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 alpha-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 F(1alpha) to 4,696 +/- 533 pg/ml.


CONCLUSIONS
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.
Du
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JDRF International Center for Diabetic Complications Research, Albert Einstein College of Medicine, Morris Park Avenue F-531, Bronx, NY 10461, USA.
Edelstein
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Brownlee
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D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D004359:Drug Therapy, Combination; D017127:Glycation End Products, Advanced / Q000378:metabolism; D006595:Hexosamines / Q000378:metabolism; D006801:Humans; D006943:Hyperglycemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D013831:Thiamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D008063:Thioctic Acid / Q000008:administration & dosage / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
D017127:Glycation End Products, Advanced; D006595:Hexosamines; D008063:Thioctic Acid; D003577:Cytochrome P-450 Enzyme System; D019746:Intramolecular Oxidoreductases; C022461:prostacyclin synthetase; D013831:Thiamine; C013835:benphothiamine