Report Date: November 2012
The following abstract presents results of a study conducted by a contract laboratory for the National Toxicology Program. The findings have not been peer reviewed and were not evaluated in accordance with the levels of evidence criteria established by NTP in March 2009. The findings and conclusions for this study should not be construed to represent the views of the NTP or the U.S. Government.
Type 1 diabetes is a significant health concern with a global increase in incidence of 3% per year. In addition to genetic factors, environmental triggers are also involved in the development of type 1 diabetes. Among the environmental xenobiotics, endocrine active compounds such as genistein may have the potential to modulate development of the disease. GEN is a major isoflavone in many soy products and is consumed in supraphysiologic levels as nutritional supplements and pharmaceuticals.
The objective of this study was to determine if GEN had the potential to modulate the progression of type 1 diabetes in non-obese diabetic MRKTac NOD mice when administered by gavage once daily for 180 days. Five groups of mice (approximately 24 animals/group; 6-7 weeks of age) were utilized: naïve control, vehicle control (25 mM Na2CO3), and three GEN treatment groups (2 mg/kg, 6 mg/kg, and 20 mg/kg body weight). Mice were maintained on a soy- and alfalfa-free diet during the study to minimize the contribution of dietary phytoestrogens and were monitored for blood glucose changes every week. When compared to the vehicle control, exposure to GEN at 2 mg/kg produced significant decreases ranging from 55% to 79% in the incidence of diabetes (blood glucose ≥ 250 mg/dl) and severe diabetes (blood glucose ≥ 400 mg/dl) starting at week 14 of the study. Significant decreases in the incidence of diabetes were observed starting at week 16 for the GEN dose groups of 6 mg/kg and 20 mg/kg; significant decreases in the incidence of severe diabetes were observed starting at week 18 and 17 for the GEN dose groups of 6 mg/kg and 20 mg/kg, respectively. Overall, treatment with GEN did not significantly affect body weight.
Taken together, these results indicate that oral exposure to GEN delayed the development of type 1 diabetes in female NOD mice fed a soy- and alfalfa-free diet.