Monday, December 22, 2008

IN MANAGEMENT OF T2DM, IS LOWER HbA1c BETTER?

Ever since the UKPDS study, the standard teaching was that we should control blood sugar to almost normal levels. That good control if blood sugar in T2DM, will reduce micro-vascular disease. We were all trying to get HbA1c to 7% or lower. This was the era when control of diabetes were measured in terms of blood sugar and also HbA1c ( both biochemical values ), with little attempt to study the relationship of good biochemical control, the link was all on the data from UKPDS.
Well, the 2000 era, has since more and more studies showing that good biochemical control may not result in better clinical outcome. It is also important to note that endocrinologist ( diabetologist ) like to deal with good biochemical control, and cardiologist ( diabetes is a cardiac disease ), like to talk about clinical ( patient outcomes ), otherwise called hard outcomes. We cardiologist like to deal with death ( cardiac, non-cardiac ), heart attack rates, angina rates, stroke rates, revascularisation rates, limb amputations,etc.
The Dec 17th, electronic online version of the New England Journal of Medicine, published the Veterans and Diabetes study ( VADS ), which studied 1800 veterans with diabetes for an average pf 11 years, treated them either to standard control ( HbA1c less than 9% ) and intensively ( HbA1c less than 6% ). The patients were treated with either metformin and rsiglitazone ( in those who were obese ) or glimepiride and rosiglitazones ( in those who were not obese ). Those still not controlled were given insulin to achieve the target control. They were followed for an average of 6.5years. The rsults showed that there were no difference in the hard outcomes ( MACCE ) and also micro-vascular complications. So, now we have three major, well conducted clinical ( ACCORD, ADVANCE, VADS ) which showed that intensive sugar, HbA1c control did no better than standard, average control. In this case, the lower HbA1c control did not result in better outcome. We must remember that intensive sugar control must also carry with it the greater risk of hypoglycemia.
During my ward-round and referrals, I still see diabetologist doing glucometers three to four times a day, to try and achieve good glycemic control. I wonder why?
What could be the possible reasons for these findings? Why does intensive sugar control not result in better outcome?, afterall, it is high blood sugar that is the cause of all the diabetic problem, Well, the most obvious reason, could be that if you study patients with longstanding diabetes, where the damage are already established, then ideal sugar levels may not make much difference. Perhaps, the results could be different if the studies were done with more recent onset diabetes. We do not yet know that.
Well, at the moment, the data seem to suggest that intensive HbA1c control may not necessarily result in better hard. clinical outcome. Of course, this is how we cardiologist see it.

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