Glucose Control in Acute Events: Where Are We?

Controversy Continues on How Low We Should Go

Leszek Czupryniak, MD, PhD; Peter Gaede, MD, DMSci


October 24, 2012

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Leszek Czupryniak, MD: Hello. My name is Dr. Leszek Czupryniak, from the Medical University of Lodz in Poland, and I am speaking from the 40th Annual Meeting of the European Association for the Study of Diabetes (EASD) in Berlin. My guest today is Dr. Peter Gaede. I hope you are very familiar with his name, because he was one of the main investigators in the Steno-2 study,[1] which showed for the first time that treating diabetes in a multifactorial can achieve a significant reduction in cardiovascular risks. You spoke about a very important subject, which is what diabetologists should do and what they should know about their jobs during acute coronary syndrome in patients with diabetes. A whole session was devoted to this subject. What can you tell us about this area today?

Peter Gaede, MD, DMSci: Our role as diabetologists focuses mainly on glucose control. Of course, you have to treat all the risk factors, as we showed in the Steno-2 trial, but the major challenge today is what to do about glucose.

Dr. Czupryniak: That is probably the most controversial issue in this area. We don't discuss lipids or blood pressure as much as we discuss glucose.

Dr. Gaede: No, and it is because one of the disadvantages with the intensified glucose control is that we see a lot of hypoglycemia, so this was, in general, what the topic was about. If you look at old observational data, you see a clear correlation between mortality and high levels of glucose during an acute myocardial infarction and in critically ill patients in an intensive care unit. The idea has long been that if you start very early to control glucose, right after the infarction or right after the acute illness that brought the patient to the intensive care unit, that you could reduce mortality or morbidity in the long term. We have been blessed with a couple of randomized trials in the last year, and going back to 2001 in the surgical intensive care unit. The van den Berghe studies[2] are pretty famous in this area, and in fact what they did was a randomized study of patients in the intensive care unit and provided very intensified glucose control.

Dr. Czupryniak: It was a huge study -- 1500 patients.

Dr. Gaede: It was quite large, and the targets were also very tight also: less than 6.1 mmol/L. That was what they aimed for, and they found that mortality was reduced both in the intensive care unit but also in hospital mortality, and of course it brought great joy to all of us who were true believers that the glucose has a role in that.

Dr. Czupryniak: But these results were not confirmed later on, and that's where the controversy is.

Dr. Gaede: Exactly. This group conducted another study in the medical intensive care unit which didn't show such marked results. Some smaller secondary endpoints had positive results, and then finally everything was turned the complete opposite way with another very large trial called NICE-SUGAR,[3] which enrolled more than 4000 patients, also in intensive care units or after myocardial infarctions. It didn't matter what brought patients to the intensive care unit, and surgical patients were included. They randomly assigned the patients to 2 groups: a "loose" group, in which they aimed for a glucose level of 8-10 mmol/L, and also a very intensive group, with goals like those in the van den Berghe study. Surprisingly, they found exactly the opposite result: Mortality was clearly higher with lower glucose control.

Dr. Czupryniak: Where are we today? What would be your recommendation today during an acute event or a myocardial infarction? How should we look at the glucose control of these patients?

Dr. Gaede: It's difficult to say. If you want to be very evidence-based, we don't have much evidence that tight glucose control actually helps. So the recommendation today is that we have taken the goals from the control group in the NICE-SUGAR trial and said, "Well, that's safe." It's because we still have this belief that glucose control is important, because you know that from the epidemiologic trials. And then again the problem is that when you go low, you have episodes of hypoglycemia. If you can avoid hypoglycemia you can go low, but the problem is that when you just give it to a group as a whole, you will have a lot of hypoglycemia, and hypoglycemia in the NICE-SUGAR trial (which was just published 2 weeks ago in the New England Journal of Medicine[4]) is clearly correlated to mortality.

Dr. Czupryniak: You don't recommend 110 mg/dL as in the Belgian study? Would you rather use 140 mg/dL?

Dr. Gaede: A goal of 140-180 mg/dL would be appropriate if we are talking about mg/dL. In mmol/L, it would be 8-10 mmol/L.

Dr. Czupryniak: Do you think it will change? Do you think that more studies will be done in this area, or would we rather stay within this 140-180 mg/dL threshold?

Dr. Gaede: We have to see more studies because it is a controversial issue. If we are talking about patients with myocardial infarction, that is a completely different setting. We need more studies, and one good thing, at least, is that we have new insulins that might have the benefit of not causing as much hypoglycemia. Other drugs coming out on the market need to be examined -- for example, the GLP-1 analogs. In smaller studies, the injection of GLP-1 analogs right after a coronary intervention produced some positive results, but these need to be confirmed in larger randomized trials.

Dr. Czupryniak: The size of the infarction might be smaller. There are some promising data. The issue is far from being resolved at present. Next year we have to go to another conference, and we can promise that we will try to discuss this issue favorably because it really affects every patient we see on a daily basis.

Dr. Gaede: You are absolutely right.

Dr. Czupryniak: Thank you very much for sharing your thoughts and knowledge on this really hot topic in diabetes care. Thank you, Peter.

Dr. Gaede: Thank you.