<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.
<International Diabetes>: Professor Pan， at this year’s IDF was there anything new regarding this area of postprandial hyperglycemia and cardiovascular disease risk and it’s relation to oxidative stress?
Prof. Pan: Surely the guidelines from IDF ask clinicians to pay more attention to postprandial glucose and also to initiate some preventative interventions against postprandial hyperglycemia. There was also information addressing patients classified as pre-diabetic， for example IGT or impaired glucose tolerance， with blood sugars between normal and the diabetic region normally associated postprandial hyperglycemia region. Some new information at the meeting stressed that missing some of this clinical information related to postprandial hyperglycemia and miss this particularly high-risk population. Because these pre-diabetics are in the so-called IGT stage， these patients present with abnormal postprandial hyperglycemia but may only be categorized as pre-diabetic when looking at other criteria. Early data suggests that the early diagnosis of these patients with postprandial hyperglycemia also have high risk of developing cardiovascular disease. This is why IDF included this in the most recently published guidelines.
<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.
<International Diabetes>: Professor Pan， are there other tests in China to monitor fluctuations in glucose besides continuous glucose monitoring systems (CGMS)? Could you tell us a bit about the present situation in China for monitoring postprandial glucose?
Prof. Pan: CGMS is very useful for monitoring variations in glucose. There is another problem in China because CGMS is not included in state insurance reimbursements， which means if we use it we should ask patients to pay by themselves. Therefore it is quite uncommon for us to use this method. If a patient’s glucose is poorly controlled it would suggest there would be significant variation. If patients have hypoglycemia than we can choose CGMS for monitoring glucose and glucose level variation. We do use CGMS for GDM since this condition requires the strict control of blood glucose. Especially if there is some indication in a particular patient to choose CGMS then we certainly will use it whenever possible.
<International Diabetes>: Professor Holman， you just mentioned several agents， acarbose and nateglinide. From the STOP-NIDDM trial it was suggested that acarbose significantly reduces the risk of myocardial infarction， cardiovascular events， and some have even said it reduces hypertension. However， the NAVIGATOR study with nateglinide it didn’t seem to show an effect in reducing diabetes or improving heart disease. With these different glycemic drugs we see different results. Do we need to pay more attention to characteristics and mechanisms of these drugs in patients who also have diabetes?
Prof. Holman: Absolutely. We now know from NAVIGATOR that simply reducing postprandial glucose with nateglinide is ineffectual. There is an interesting study from Japan recently which shows that if you compare nateglinide with acarbose you get the same degree of glucose lowering after a test meal， but with acarbose you see a distinct improvement of flow mediated dilation， which you don’t see with nateglinide. That is just one example of a class of agents that has an effect that is not directly linked to the glucose. Agents like acarbose and new classes like DPP-4 inhibitors and GLP-1 agonists with all the incretin biology， do offer a more complex intervention， which may well have additional benefits that we are now testing with the T-COSS and E[下一页] [1] [2] [3] [4] [5]