Lowering the blood sugar of type 2 diabetics to a level close to normal would be good for the kidney, but would not work for the heart!
How far can you lower blood sugar in order to obtain the best prevention of cardiovascular risks in type 2 diabetics? Three studies presented at the ADA congress (San Francisco, June 16-19, 2008) had to answer this question. The common denominator of this work was to aim for an optimal HbA1c level to prevent cardiovascular events. With one observation: cardiovascular damage in type 2 diabetic patients is clearly associated with their blood sugar level. It was then logical to think that bringing the sugar level close to normal would have favorable consequences on the heart and the vessels. It remained to prove it.
One of the “Advance” studies (1), involving 11,000 patients treated intensively for five years, concludes that drastically lowering blood sugar (glycemic target of 6.5% HbA1c) decreases the risk of serious complications, especially renal. The other “Accord” study (2) (glycemic target at 6% HbA1c) shows, for its part, an unexplained excess mortality in patients treated even more intensively. These results led to the premature discontinuation of one arm of the trial, the patients having integrated the standard treatment. These two studies and a third come to the same conclusion: intensive treatment of type 2 diabetics does not significantly reduce cardiovascular risks. The whole question is how blood sugar is involved in macrovascular events. For Prof. Bruno Vergès (Dijon University Hospital), it’s a matter of time. “It probably takes more time to demonstrate a real benefit on the cardiovascular, more than the 5 years of follow-up of the studies”. However, should the drop in blood sugar be moderated? Certainly not, says Professor Vergès. The Advance study does not show any deleterious effect of lowering blood sugar and shows an undeniable major benefit in terms of reducing the risk of nephropathy. This is why the management of type 2 diabetics must remain intensive with HbA1c objectives lower than or equal to 6.5%, which are those of the French recommendations. ADA Special Envoy, Dr Sophie Lemonier (1) Advance (Action in Diabetes and Vascular disease, perindopril ANd indapamide Controlled Evaluation) (2) Accord (the Action to Control CardiOvascular Risk in Diabetes)
Questions to Prof. Bruno Vergès, endocrionology department, Dijon University Hospital
A significant advantage on the risk of kidney complications
Does the Advance study show decisive results? Prof. Bruno Vergès. Advance’s results for the glucose arm showed a significant 14% decrease in microvascular events with a markedly reduced risk of onset and worsening of nephropathy. It is interesting to note that the intensive group had on average at the end of the study an HbA1c of 6.5% and the control group an HbA1C of 7.3%. One of the major lessons of the Advance study is to show that a reduction in HbA1c below 7.3% to obtain an average of 6.5% allowed a significant advantage on the risk of renal complications. Important point was that the weight gain was very moderate of 0.75 kg over the duration of the study.
But could the benefits recorded on the kidney not have consequences for the heart? Pr BV Many speakers have pointed out that the significant reduction in nephropathies should inevitably lead to a reduction in cardiovascular risk in the medium and long term. It is in fact known that diabetic patients with nephropathy regardless of the level of microalbuminuria, macroalbuminuria or end-stage renal failure have an extremely increased cardiovascular risk. So, mathematically, there should be a significant reduction in cardiovascular risk a few years later. But the 5-year period was certainly too short to demonstrate this decrease.
What is your hypothesis regarding the deaths in the Accord study? Pr BV. Several avenues are advanced. Possibly, hypoglycaemia, even if the statistical analysis does not show them clearly. But also the speed of drop in blood sugar levels since in the intensive group, we saw a 1.4% decrease in HbA1c over the first 4 months of the study, while this decrease was much more moderate in the study. Advance. We also observed in the Accord study a significant increase in weight on average of 3.5%: 27% of patients in the intensive group gained more than 10 kg during the study. It is therefore questionable whether this weight gain was not a factor in mortality. The question is wide open. Discussions also focus on the treatments used: the vast majority of patients were on rosiglitazone, and a large proportion received the combination of insulin plus rosiglitazone, which exposes them to possible deleterious effects.