<International Diabetes>:   In addition to postprandial hyperglycemia， blood glucose fluctuations can be closely related to cardiovascular disease risk.  What do you think is the impact of blood glucose on cardiovascular disease?  Is the impact of blood glucose fluctuations on cardiovascular disease greater than that of just simple postprandial hyperglycemia?  Is the impact the same or different?  Also， in clinical practice， how could we try to better effectively reduce these blood glucose fluctuations?
    Prof. Holman:   Postprandial hyperglycemia is an independent risk factor for cardiovascular disease although we don’t know exactly how it operates.  It may not just be the height of the glucose fluctuation but just be a simple measure of variability.  As new techniques like continuous glucose monitoring become available we need to uncover and explore these.  There are different treatments that can improve or reduce the variability.  For instance， agents like acarbose， that don’t cause hyperglycemia， or DPP-4 inhibitors like setoglyptin， will provide a smoother glucose profile than using secretegogue like sulphanourea.  This is an area that needs to be explored.  The NAVIGATOR study that used a short acting secretegogue， protectinide， just to reduce glucose after meals did not show a benefit.  I take that to mean that the mechanism is not simply the height of the glucose.  The height of the glucose is telling us something else.  It is acting as a surrogate for other glucose abnormalities.  Variability is just one of the components that need to be explored.  There are good data from Monier， which have shown that the variability relates to the highest levels of oxidative stress.  We have a causal explanation but just aren’t clear yet whether it is the right one.  This is an area rich for new clinical trials.