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The target hemoglobin A1c of less than 7% should remain the general goal for nonpregnant adults with diabetes, despite recent results from three large randomized trials showing that intensive glucose lowering did not reduce the risks of cardiovascular disease in people with longstanding type 2 diabetes.

But glycemic targets that are either more or less stringent than that standard may be prudent for certain individuals with diabetes, according to a position statement issued jointly by the American College of Cardiology, American Diabetes Association, and American Heart Association and published online in the journals of each organization: the Journal of the American College of Cardiology, Diabetes Care, and Circulation.

The three organizations conducted a careful reexamination of glycemic control guidelines in light of the findings from the Action to Control Cardiovascular Risk in Diabetes (ACCORD), the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and the Veterans Affairs Diabetes Trial (VADT). All showed no significant reduction in cardiovascular outcomes with intensive glucose control, but the ACCORD caused particular concern--and was halted early--because it showed a 22% increase in mortality among subjects randomized to a strategy of very intensive glycemic control with a target HbA1c of less than 6% (N. Engl. J. Med. 2008;358:2545-9).

Nonetheless, "The evidence obtained from ACCORD, ADVANCE, and VADT does not suggest the need for major changes in glycemic control targets, but rather additional clarification of the language that has consistently stressed individualization," Dr. Jay S. Skyler and his associates wrote (Diabetes Care 2009;32:187-92). Clarifications include:

PITo prevent microvascular and neuropathic complications in people with both type 1 and type 2 diabetes, the HbA1c goal for nonpregnant adults in general remains less than 7%. This recommendation is based on robust data from long-term studies including the Diabetes Control and Complications Trial (DCCT) and the United Kingdom Prospective Diabetes Study (UKPDS).

PIThe general HbA1c goal of less than 7% also "appears reasonable" for prevention of macrovascular disease among those with recent onset of diabetes, based on long-term follow-up of the DCCT and UKPDS cohorts.

PIFor selected individual patients, even lower HbA1c goals than the general goal of less than 7% might be reasonable, provided that this target can be achieved without significant hypoglycemia or other adverse effects of treatment. Such individuals might include those with short duration of diabetes, long life expectancy, and no significant cardiovascular disease. This recommendation was based on subgroup analyses of the DCCT, UKPDS, and the microvascular evidence from the ADVANCE trial, which showed a reduction in albuminuria with intensive glucose lowering.

PIConversely, less stringent HbA1c goals may be appropriate for patients with a history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, or extensive comorbid conditions or those with longstanding diabetes in whom the general goal is difficult to attain despite diabetes self-management and education, appropriate glucose monitoring, and effective doses of multiple glucose-lowering agents including insulin.

PIFor cardiovascular risk reduction in patients with diabetes, providers should continue to follow the evidence-based recommendations for blood pressure treatment, lipid-lowering with statins, aspirin prophylaxis, smoking cessation, and healthy lifestyle behaviors delineated in the ADA Standards of Medical Care in Diabetes (Diabetes Care 2008;31[suppl 1]:s12-54) and the AHA/ADA guidelines for primary CVD prevention (Circulation 2007;115:114-26).

A substudy of VADT presented at the ADA's annual meeting in June suggested that individuals earlier in their history of type 2 diabetes had the most benefit of improved glycemic control, noted Dr. Daniel Einhorn, head of the Sharp Diabetes Treatment and Research Center, San Diego.

"The key is not to throw out the baby with the bathwater. The VADT and ACCORD suggest that some populations may not benefit from tight glycemic control and there may be risks associated with tight control in these same populations, i.e., with cardiovascular disease and/or increased risk of hypoglycemia. This does not detract from the wealth of information that good glycemic control confers benefit on microvascular disease and, given a long enough window, cardiovascular disease," said Dr. Einhorn, also on the AACE board of directors.

Proving a CVD benefit from glycemic control takes much longer than does blood pressure or lipid control, he added.

Seven of the eleven members of the document's writing committee disclosed financial conflicts with companies that manufacture diabetes-related products.

When asked to comment on this article, Dr. Vivian Gahtan, SUNY Upstate Medical University College of Medicine, Syracuse, N.Y., stated: "Evidence indicates that glycemic control is important in the appropriate management and general health of the patient with diabetes mellitus. A building body of literature exists which shows that glycemic control is important in the outcome of the surgical patient in the perioperative period. The hemoglobin A1c has become an important marker reflecting glycemic control. Putting the results of these trials suggesting the hemoglobin A1c may not decrease the macrovascular cardiovascular risk in patients with long-term type 2 diabetes mellitus must be put into context.

"These findings do suggest a patient population that may not benefit from tight glycemic control. The microvascular and neuropathic benefits remain and keeping the hemoglobin A1c less than 7% appears prudent. Ongoing trial information on larger patient populations will allow us to truly understand the effects of controlling the hemoglobin A1c on macrovascular disease in patients with type 1 diabetes and those patients who have been well controlled from the time of diagnosis of type 2 diabetes.