Reactive Oxygen Species in the Pathogenesis of Diabetic Complications
Condition: Type 1 Diabetes
MeSH terms: Diabetes Complications
Study type: Interventional

Summary: 
      Benfotiamine blocks three major pathways of hyperglycemic damage and prevents experimental
      diabetic retinopathy and incipient nephropathy in these models. In cultured vascular cells,
      it also reduces aldose reductase gene expression, activity, and sorbitol levels. It does so
      by activating the enzyme transketolase. α-lipoic acid, a potent antioxidant, has also been
      reported to reduce both diabetic microvascular and macrovascular complications in animal
      models. To determine whether benfotiamine in combination with α-lipoic acid would normalize
      markers of ROS-induced pathways of complications in humans, we performed a pilot study in
      subjects with Type 1 diabetes using one daily dose of benfotiamine in combination with
      α-lipoic acid.
    

Detailed description: 
      The glycemic status of study patients was assessed by measuring baseline values of HbA1c,
      fructosamine, and fasting plasma glucose. Mean HbA1c was 8.7+ 0.7%, mean fructosamine was
      421+29 mg/dl (normal range 174-286 mg/dl), and mean fasting blood glucose was 198+44 mg/dl.

      At day 0, subjects levels of markers of two benfotiamine-sensitive pathways were determined:
      intracellular advanced glycation endproduct (AGE) formation, as reflected by a marker of
      increased intracellular methylglyoxal adducts in endothelial cells, angiopoietin 2 and
      hexosamine pathway activity, measured by determination of N-acetylglucosamine-modified
      protein in circulating monocytes. PKC activity in circulating monocytes could not be measured
      because the amount of blood required exceeded that approved by the Committee on Clinical
      Investigations. Serum levels of 6-keto-PGF-1 , a stable product produced by the nonenzymatic
      hydration of the antiatherogenic mediator prostacyclin were also determined. Subjects then
      took benfotiamine 300 mg twice a day, (Advanced Orthomolecular Research, Calgary, AB,CANADA)
      and slow-release α-lipoic acid (600 mg twice a day) (MRI, San Francisco, CA) for 28 days.
      Blood was obtained at day 0, day 15, and day 28.

      Data were analyzed using 1-factor analysis of variance to compare the means of all the
      groups. The Tukey-Kramer multiple comparisons procedure was used to determine which pairs of
      means were different.
    

Intervention name(s): benfotiamine, α-lipoic acid
Intervention type(s): Dietary Supplement
Intervention description(s): benfotiamine 300 mg twice a day, (Advanced Orthomolecular Research, Calgary, AB,CANADA) and slow-release α-lipoic acid (600 mg twice a day) (MRI, San Francisco, CA) for a total duration of four weeks
Other intervention name(s): benfotiamine 300 mg .slow-release; α-lipoic acid (600 mg twice a day)
Intervention MeSH terms: Thioctic Acid; Benphothiamine
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: hyperglycemia; diabetic complications; advanced glycation endproducts; hexosamine pathway; prostacyclin synthase; reactive oxygen species