This generation’s diabetic control is preceded by the ever-present adjective “intensive.” Although a lower A1c seems to be a rational, and in many instances a proven target for type 2 diabetes with its constellation of micro- and macrovascular complications, are there downsides when prescribing exactly how low one’s A1c should go? A recent study puts a different spin on A1c targets.1
Remember the era describing consequences of hypertensive blood pressure lowering as a “U-shaped” proposition. That is, mortality increased at 2 levels, a blood pressure that was too high as well as a blood pressure that was treated to too low a level. It was assumed that an excessively high blood pressure was bad for obvious reasons. So, lowering blood pressure was a good thing. However, it was suspected that overly aggressive lowering of blood pressure might decrease perfusion to compromised coronary vessels thereby increasing cardiovascular mortality.
The study on diabetic therapy targeting A1c levels identified a “U-shaped” all-cause mortality model in people treated for type 2 diabetes mellitus. The patients, all 50 years of age and older, comprised 2 groups: 27,965 individuals who were on therapy with combination oral agents and 20,005 individuals on insulin-based regimens. The primary outcome measure was all-cause mortality. Followup was from November 1986 through November 2008. The patients were retrieved from the United Kingdom General Practice Database.
Intensive level A1cs, that is, a median of 6.4%, were at a 52% greater risk of dying! Conversely, individuals who were “uncontrolled,” that is, a median A1c of 10.5%, had a 79% greater risk for death from all causes! Essentially, a “U-shaped curve” was demonstrated in that mortality had 2 peaks—a high and low A1c. The lowest risk for mortality resided in the group of individuals with a median A1c of 7.5%, a target above what is currently recommended. The authors suggested a change in the accepted target A1C for individuals with type 2 diabetes mellitus. They also observed that the difference in regimens between the 2 groups (oral-based versus insulin-based therapies) meant that it is the A1c per se not the regimen accounting for the observed outcomes.
Commentaries on the data suggested caution in interpretation of the results.2 Other studies have not implicated tighter A1c levels with increased mortality, vascular or all-cause. So there will not be an immediate change in how physicians “do business” controlling A1c levels in type 2 diabetes mellitus. But, ongoing trials, large like this study may change the concept of lower is always better regarding A1c levels and diabetic control. This author already suspected as much in his geriatric cohort with CKD-3 or worse with compromised vision.