For patients with type 2 diabetes mellitus, logic would dictate that tight glycemic control would reduce CVD events and improve outcomes. However, clinical trials have not definitively established a connection between high or low glycated hemoglobin (A1C) levels and decreased CVD event risk. In the current study, Gregory A. Nichols, PhD, from Kaiser Permanente Center for Health Research in Portland, Oregon, and colleagues examined rates of CVD hospitalizations and all-cause mortality in a general diabetes population to determine if there was any threshold for the risk reduction.

They included 26,673 patients with type 2 diabetes in the study; investigators categorized the study participants according to mean level of A1C during an average 6-year follow-up (grouped into quartiles). Patients in lower A1C categories tended to be older and have slightly shorter duration of diabetes compared with patients in the higher A1C categories. Those in lower A1C categories were more likely to have macrovascular complications and less likely to use insulin. When the investigators looked at patient characteristics across A1C categories analyzed for CVD hospitalizations or all-cause mortality, however, the results were nearly identical.

In terms of incidence rates, 2,176 patients (8.2%) experienced a CVD hospitalization, 3,601 (13.5%) died, and 4,853 (18.2%) experienced either outcome. Patients with a higher A1C (>9.0%) were most likely to experience CVD hospitalization, followed by A1C 8.5–8.9% and A1C <6.0%. Patients with A1C <6.0% also had the highest rates of mortality.

The overall relationship between mean A1C and CVD hospitalizations and all-cause mortality was approximately U-shaped. After adjusting for known CVD risk factors, complications, and diabetic medications, rates of the composite outcome were also statistically significantly greater among the two highest and the two lowest A1C categories.

"Other studies suggest a threshold effect, such that risk of CVD events and mortality is increased at higher levels of A1C, but neither increased or decreased below 7%," Dr. Nichols and colleagues noted. Although their study's observational design precludes the establishment of a causal relationship, the data support the concept of a "sweet spot" for controlling glycemia in diabetic patients. Perhaps, they suggest, a more patient-centered approach to glycemic control should be adopted, allowing for less stringent A1C targets for specific patients.

Nichols GA, Joshua-Gotlib S, Parasuraman S. J Am Coll Cardiol. 2013 May 8. [Epub ahead of print]

Keywords: Glycated Hemoglobin A, Incidence, Risk Reduction Behavior, Diabetes Mellitus, Type 2, Logic, Hospitalization

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