What’s the Right HbA1c Target?

In my most recent post I mentioned the matter of an on-going debate over the proper target for HbA1c values. I went back and listened again to the debate at this year’s EASD conference on the “right” A1c target. (You can find it by starting at the EASD webcast page and searching for “Berger”.)

The talks by Drs. Irl B. Hirsch and Andrea Siebenhofer-Kroitzsch are chock full of information, and I’ll summarize them here. I’ve also taken the liberty of including some of their slides. Any mistakes in recapping these presentation are entirely due to my limited knowledge of epidemiology and shouldn’t reflect on the good doctors arguments. Also, there’s a lot of statistics in these presentations; and while I studied mathematics as an undergraduate, I went the abstract math route and am rubbish with statistical jargon.

First, Dr. Hirsch advocated for a target of 6.5%.

  • An A1c of 6.5% works out to an average of 144 mg/dL or 7.8 mmol.
  • But 6.5% actually has a fairly large overlap with 7.0% if you use the 95% confidence intervals of each.
  • So, there’s not that much of a difference between 6.5 and 7.0%.
  • 6.5% is protective. There’s a small but significant reduction in the risk of complications with an A1c below 7.0%.
  • And there’s an “exaggerated increased risk of hypoglycemia” below 7.0% for type 1.
  • The DCCT (which suggested that there was increased risk of severe hypoglycemia with better A1c) was reported in 1993. It’s a different time now. JDRF continuous glucose monitor (CGM) studies show that risk is way down at all levels of A1c to the same as very high A1c.
  • Lower A1c values are protective for type 2 as well, but treatment is a “moving target.”
  • No matter what you target, the actual is going to be higher (often by as much as 0.5%). — So why not aim lower?
  • Furthermore, doctors have been told “additional action” is required if the A1c is more than 1.0% over the target — so people with diabetes (PWDs) often aren’t getting told to change until well into the danger zone.
  • Does the ACCORD study indicate that trying to achieve normal A1C results in increased mortality? [Yikes!]
  • As in other trials, a higher average A1c in ACCORD is associated with a higher risk of death: +22% for each 1% of A1c.
  • And with intensive treatment, the risk of death continues to decrease below 7.0% — Not so with “standard treatment strategy.” [I believe the "intensive treatment" group aimed at lower A1c.]
  • Moreover, the people with the highest risk of mortality in the study, were the people with the lowest decline in A1c.
  • The causes of death in ACCORD weren’t differentiated, though.
  • Of course, the target value is individualized based on other factors. “Clinical judgement always trumps guidelines.” “If you can’t get there, don’t push it.”

Dr. Andrea Siebenhofer-Kroitzsch used meta-analysis of several different diabetes trials to argue that we can’t tell definitively whether improving glycemic control (as measured by a lower A1c) actually helps.

  • There are many other factors that along with A1c confound what causes improved/worse outcomes. Factors such as social status.
  • So far, there are only seven randomized, controlled trials on A1c (DCCT is by far largest with 1441 patients).
  • The age of people in the DCCT were quite young, so it was hard to see macrovascular complications (such as heart disease) directly from the study.
  • And, the ACCORD study had to be stopped because intensive treatment had a higher mortality for some groups. [Seriously?]
  • Some studies showed more hypoglycemia and more weight gain with aggressive treatment.
  • Other changes are more effective in preventing complications: blood pressure, cholesterol reduction.
  • Don’t confuse intensive self-management with A1c.
  • Tight glycemic control is very beneficial for young people with type 1. Admits that people with type 1 need tight glycemic control because of length of treatment. [But type 2 is occurring much earlier in age, one audience member reminded us.]
  • Lots of open questions about the value of glycemic control.
  • Individualized treatment is more important, almost suggesting letting patients to set their own targets as long as a minimum level of outcomes are met.

Here are my reactions and some questions I had while listening to the session:

  • It’s good to see that the increased use of CGM technology can dramatically reduce the number of severe hypoglycemia episodes. Given what it costs to go to the ER, there’s another argument in favor of covering CGMs and supplies more widely by insurance carriers.
  • The meta-analysis was very . . . meta. Consequently it pushed very hard on the difference between “proof” and “connection.” A lower A1c may suggest better outcomes, but it doesn’t prove that the lower A1c caused it. I get this, but the data are compelling to me.
  • Almost all of Dr. Siebenhofer-Kroitzsch charts suggest favoring more intensive treatment, although that seemed to contradict the core of the presentation. Perhaps I don’t know how to read them correctly? [Mo meta, Mo problems.]
  • Does the fact that clinical trials never met their A1c targets mean that people with diabetes (PWDs) are going to feel even worse about not meeting A1C targets if the target is lowered to 6.5%?

Ultimately, based on the questions and comments from the audience, the debate sounded like a draw. I think I’m in Dr. Hirsch’s camp, and I would ultimately like the lowest A1c I can safely get; but I don’t think I’ve ever really been close to breaking below 6.5%. So maybe Dr. Siebenhofer-Kroitzsch’s camp and the ADA have a point worth considering carefully when looking for a number to cover all of us.

Some of Dr. Hirsch’s slides:

Some of Dr. Siebenhofer-Kroitzsch’s slides:

This entry was posted in Diabetes, Fodder for Techno-weenies, From the Yellow Notepad, NaBloPoMo, NaBloPoMo 2009. Bookmark the permalink.

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