Poster Presentation Australian Diabetes Society and the Australian Diabetes Educators Association Annual Scientific Meeting 2014

The persisting proinflammatory effects of transient glucose exposure are equivalent to that observed in chronic hyperglycemia with diabetes (#219)

Chris Tikellis 1 , Raelene Pickering 1 , Merlin Thomas 1
  1. Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia

Diabetes casts a long shadow over the lives of many people. It is now clear that even transient hyperglycemia can have long-lasting effects on the development and progression of diabetic complications. This ‘metabolic karma’ may explain why many patients with pre-diabetes manifest diabetic complications, including renal disease, and why even brief periods of poor control in patients with diabetes may have a sustained adverse legacy. To explore this phenomenon, male C57Bl6 mice were randomised to receive four sequential injections of D-glucose (3g/kg IP) or an equivalent volume of saline or L-glucose delivered two hours apart. This protocol produces a sustained elevation in plasma glucose levels (15-25mM) for 8 hours, after which time no difference in plasma glucose levels is detectable between treated and control mice. Glomeruli isolated from mice one week after transient glucose exposure showed persistent up-regulation of ICAM-1, VCAM-1, MCP-1 and NFKB expression. Glomerular leukocyte recruitment was also increased as indicated by expression of CD11b and FACS analysis.   Aortae taken 1-week after glucose exposure also demonstrated up-regulation of adhesion molecules and increased adhesiveness when exposed to labelled human leucocytes ex vivo. Repetition of the transient hyperglycaemia protocol every two weeks for ten weeks in complications-prone apolipoprotein E KO mice led to the development of atherosclerosis, renal damage and albuminuria comparable to that observed in streptozotocin induced diabetic mice. These experimental data support the hypothesis that glucose excursions have longstanding adverse effects, and support the call for their early treatment.