Poster Presentation The Annual Scientific Meeting of the Australian Diabetes Society and the Australian Diabetes Educators Association 2013

Reduced autoimmune diabetes incidence via glycotoxin lowering therapies is time dependent in an experimental diabetic mouse model (#274)

Danielle J Borg 1 , Felicia (Yih Teng) Yap 2 , Amelia K Fotheringham 1 , Brooke E Harcourt 1 , Domenica McCarthy 1 , Micheal S Ward 1 , Robyn Slattery 3 , Melinda Coughlan 2 , Philip Kantharidis 2 , Josephine M Forbes 1
  1. Mater Research, Woolloongabba, QLD, Australia
  2. Division of Diabetes Complications, Baker IDI Heart and Diabetes Institute, Melbourne
  3. Department of Immunology, Monash University AMREP, Melbourne

The surge in type 1 diabetes within lower risk genotypes is most likely a result of environmental risk factors. Altered dietary patterns and food processing has led to increasing exposure to advanced glycation end products (AGEs) which have been shown to influence islet secretory function.  Herein we examined the effect of reducing AGE exposure with various therapies administered either as short term treatments prediabetes or long-term intervention for the remainder of life. Female NODShiLt mice (n=10/group) received either (i) No therapy (ii) a diet 4-fold lower in AGE content or (iii) the AGE lowering therapy, alagebrium chloride (ALT; 1mg/kg/day) from day 50 to 100 or day 50 to 200 of life. Mice treated with ALT from day 50 to 100 of life, had a considerable reduction in diabetes by day 200 as compared to control mice (80% vs 20%, p=0.005). Conversely, mice fed a low AGE diet from day 50 to 100 of life were not protected at day 200 as compared to control mice (80% vs 60%, p=0.35). ALT therapy improved glucose and insulin tolerance while a low AGE diet only enhanced glucose tolerance prediabetes (day 80) despite a decline in insulin sensitivity compared to control mice. Long-term administration of either a low AGE diet or ALT (day 50 to 200) prevented the development of diabetes compared to control mice (90% and 95% respectively vs 50%, p<0.05). While long-term ALT treatment improved glucose tolerance and islet secretory function, the low AGE diet improved only glucose tolerance with a decline in insulin sensitivity prediabetes compared to control mice (p<0.05). These results demonstrate protection afforded by targeting AGEs in experimental autoimmune diabetes varies depending on the type and length of therapy. Further insight into mechanisms responsible for this variation is required to better evaluate these approaches in the prevention of type 1 diabetes.