<International Diabetes>:  Firstly Professor Holman， postprandial hyperglycemia is an independent risk factor for cardiovascular disease and has been suggested as a new cardiovascular risk reduction intervention target.  Do you agree that postprandial hyperglycemia’s impact on cardiovascular disease is mainly mediated by oxidative stress?  By what mechanism does postprandial hyperglycemia increase oxidative stress and further lead to an increase in cardiovascular disease?
    Prof. Holman:  So presently I don’t think we do fully understand the exact mechanism.  The epidemiology data suggests that postprandial hyperglycemia is a risk factor for cardiovascular disease and there are several mechanisms.  The one you mentioned， oxidative stress， is related to both glucose excursions and variability after meals， as has been shown by a number of authors.  Also， there are a number of other metabolic changes， lipid dysmetabolism and endothelial function changes， any or all of which could be the causal mechanism.  I think that oxidative stress is a likely candidate and the data up to present are suggestive of this， but we have no trials where oxidative stress has been reduced that have shown benefit.  To give support to this mechanism as a causal mechanism， we need to answer that particular question.  To do this we need proper trials of outcomes.  While mechanistic studies are very helpful in supporting the design of trials and suggest hypotheses.  If there were a drug that can improve that situation then the ideal thing to do would be to test it in a randomized control trial.