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Reactive Oxygen Species in the Pathogenesis of Diabetic Complications

Information source: Albert Einstein College of Medicine of Yeshiva University
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Type 1 Diabetes

Intervention: benfotiamine, α-lipoic acid (Dietary Supplement)

Phase: N/A

Status: Completed

Sponsored by: Albert Einstein College of Medicine of Yeshiva University

Official(s) and/or principal investigator(s):
Michael Brownlee, M.D., Principal Investigator, Affiliation: Albert Einstein College of Medicine of Yeshiva University


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.

Clinical Details

Official title: The Role of the Glucosamine Pathway and Reactive Oxygen Species in the Pathogenesis of Diabetic Complications

Study design: Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Primary outcome:

intracellular advanced glycation endproducts

hexosamine pathway

prostacyclin synthase activity

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.


Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Male.


Inclusion Criteria:

- Male

- Type 1 diabetes duration between zero and fifteen years

- current insulin therapy

Exclusion Criteria:

- Female

- proliferative retinopathy

- microalbuminuria

- symptomatic diabetic neuropathy

- cardiovascular disease

- taking medications

- smoking

Locations and Contacts

GCRC, Albert Einstein College of Medicine, Bronx, New York 10461, United States
Additional Information

Related publications:

Brownlee M. The pathobiology of diabetic complications: a unifying mechanism. Diabetes. 2005 Jun;54(6):1615-25.

Starting date: February 2005
Last updated: June 23, 2008

Page last updated: August 23, 2015

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