HOUSTON — New guidelines on inpatient glycemic control issued by the American Association of Clinical Endocrinologists and the American Diabetes Association support less-intensive management goals.
The consensus statement updates more stringent guidelines released in 2004. Now, instead of glucose targets of 80–110 mg/dL for hospitalized critically ill patients, targets of 140–180 mg/dL are recommended.
For most noncritically ill hospitalized patients on insulin, premeal glucose targets should generally be below 140 mg/dL and random blood glucose values should be below 180 mg/dL. (The 2004 guidelines recommended premeal glucose targets below 110 mg/dL, with a maximal level of 180 mg/dL.) Consideration should be given to reassessing the insulin regimen if glucose falls below 100 mg/dL, while the regimen must be modified if glucose level falls below 70 mg/dL, the two organizations said in the statement, which also recommends strategies to achieve the targets.
The panel had nearly completed the document when the NICE-SUGAR (Normoglycemia in Intensive Care Evaluation and Survival Using Glucose Algorithm Regulation) study was published in March. That large, randomized, controlled trial showed increased mortality associated with intensive glycemic control targeting blood glucose of 81–108 mg/dL.
“Many people thought this statement was a knee-jerk reaction to the [NICE-SUGAR] study. But in fact, we started this process last fall,” said Dr. Etie S. Moghissi, who chaired the 10-member AACE/ADA task force that wrote the statement (Endocr. Pract. 2009;15:1–17; Diabetes Care 2009;32:1119–31).
The panel made only minor modifications based on the NICE-SUGAR findings. “Our task was really to look at all of the evidence. … We needed to come to not only reasonable and achievable, but, importantly, very safe targets,” said Dr. Moghissi of the University of California, Los Angeles.
Several recent clinical trials in critically ill patients with diabetes or high blood glucose levels have failed to show a significant improvement in mortality with intensive insulin therapy. These outcomes have raised concerns that the means for achieving specific glucose targets may play a role in adverse outcomes, particularly with regard to iatrogenic hypoglycemia.
Dr. M. Sue Kirkman, vice president of clinical affairs for the ADA, noted that “the emerging evidence from further randomized controlled trials in ICU settings called into question some of the early enthusiasm for intensive treatment targets. … But on the other hand we're also concerned that people might react to these more negative studies by letting the pendulum swing back too far. We really don't want people going back to the bad old days of ignoring hyperglycemia in the hospital, where it's clearly linked to adverse outcomes.”
Several audience members said they had successfully implemented protocols to achieve the lower targets, and asked whether they were expected to back off. One audience member asked if he would face medicolegal risk if his institution continued to use the lower targets.
Dr. Moghissi replied that hospitals are free to continue as they have been doing but should keep in mind that current evidence doesn't support it. “These are general recommendations. Medicolegally, you need to do what you think is right for your institution and what is safe.”
She added, “I think the targets recommended will be a lot easier to achieve in the majority of community hospitals.”
Other speakers reiterated that the data can't be ignored. Dr. Framarz Ismail-Beigi, professor of medicine at Case Western University, Cleveland, said, “I don't know if I'm doing any good with [tight glucose targets], but I know that when other people have tried this in a randomized clinical trial, harm has appeared. And the harm may not be linked to hypoglycemia.”
Dr. Guillermo E. Umpierrez, professor of medicine at Emory University, Atlanta, reminded the audience that benefit from intensive therapy was seen in just one randomized controlled study (N. Engl. J. Med. 2001;345:1359–67). Two other large randomized trials were stopped due to unacceptable rates of hypoglycemia, and now NICE-SUGAR shows evidence of harm.
“The data are clear. If you try to achieve [the goal of] 80–110, you don't gain more, you get more hypoglycemia, and you take the risk of increased mortality. We have to accept reality: 80–100 doesn't improve outcome and may be dangerous.”
Dr. Irl B. Hirsch, professor of medicine at the University of Washington, Seattle, summed up the panel's current stance: “Where we are with the data right now, we got it right. That's not to say that we may not reconvene in a couple of years and do this again, because we want to keep this as evidence based as possible.”
Dr. Ismail-Beigi and Dr. Kirkman stated that they had no conflicts of interest. Dr. Moghissi, Dr. Hirsch, and Dr. Umpierrez each disclosed financial relationships with several pharmaceutical companies that make diabetes-related products, as did 7 of the 10 panel members.
To see an interview with Dr. Moghissi about the guidelines, go to www.youtube.com/watch?v=iQcIUiKMckw.
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