When is tight control too tight

Well, there is pretty good evidence for getting to a normal A1C as far as preventing some complications, but it has to be balanced by the risks of getting there. I actually like the ADA guidelines which say that in general we should strive for less than 7, and on the individual level as close to normal as possible without causing hypoglycemia. So for example, if I have a new diabetic and I can get him or her to a normal A1c with lifestyle changes & pushing the dose of metformin, I should. If I have someone who is brittle & on insulin, I shouldn’t shoot for an A1C <6 or maybe even <7 because I would be dropping them too often. Also, if it takes metformin, Avandia, Byetta, & insulin to get <6, then it is probably not worth it and potentially dangerous. One of the main problems is that the bean counters want 100% compliance, but what we should really strive for is an “achievable benchmark”. Maybe the goal in ideal circumstances is getting 70% of our diabetics <7 and this is how we should be judged or compared.

I really don’t find the results of this study that surprising or inconsistent with prior studies. We’ve known for a while that hypoglycemia can be bad for you, especially if you have heart disease. Just like everything else, you have to balance the risks & benefits.

What, then, should a patient with Type II DM ask their physician about on this topic? Or not ask, wait to be told to get the A1c down lower?

There is clearly more to treating patients then treating surrogate endpoints, but there is good evidence that treating sugar is important. Dr. Roy Poses is correct that in the UKPDS study the macrovascular outcomes (heart attack) did not reach statistical significance, as the p value was = 0.05. However, this means that there was a 95% chance that it was important. Thus, other factors in addition to the sugar are also important for preventing heart disease. Statins clearly help, but since even diabetics with normal ldl’s (Heart Protection Study) showed benefit, there is more than just the ldl.
The problem with ACCORD is that they went too far. A goal of less the 6.0% is probably not a good idea. Though the details of the study have not been released, (though Avandia was cleared) I suspect the need for exogenous insulin to achieve these agressive goals will turn out to be a major factor. I find this very intersting, since the most recent ADA goals shun the milder, newer (granted more expensive) drugs in favor or tried and true insulin because of its efficacy (as well as lowe cost). Should we be surprised that the endocrinologist are pushing insulin for type 2 diabetes?
C. Lewin, I discuss what to tell patients on my blog, http://www.drmintz.com

I think there is reasonable evidence for aiming for hgba1c of 7%, if other factors such as advanced age and comorbidity aren’t in play, to prevent or retard the progression of microvascular complications. ACCORD provides strong evidence that it is dangerous for Type II diabetics with heart disease, or multiple risk factors for same, to aim for an a1c substantially below this.

These weren’t new diabetics; the average duration of (known) disease was 10 years, so I suspect many of these patients needed insulin. I don’t think any of my middle-aged or elderly, late-stage diabetics have a1cs around 6, and I don’t push any to that.

I thought the study was pretty poorly reported. But hey- drama sells! For starters- the difference in death rates was what- like 250 versus 200 people, without having the numbers in front of me. However, it seems to me that those differences are hard to justify as not related to external factors, such as previous control, length of time they had diabetes but went undiagnosed, and lipid and hypertension control.

They used oral meds extensively in the study as well, one of which was Avandia. Avandia is already under fire for it’s potential link to heart disease. I’d love to see how the study would have been different if just insulin and lifestyle changes were considered, along with aggressive treatment of hyertension and dyslipidemia.

As far as I can tell, the study also didn’t consider glucose variability. If the person was on a high carb diet and spiking up to 300 post meal, but coming back to 80 fairly quickly, that’s a lot of glucose variability, even without hypoglycemia, but can still result in a good a1c. But there’s some (weak) evidence, especially from the DCCT, that variability in bgs also contributes to complications.

I’m worried that this will be taken to far. Sure, if you’re old and something else is gonna kill you off first, keep your a1c at 8%. But what about in 30 year olds? I can picture someone saying “It’s okay that my a1c is 10%, good control kills ya!”

I’d like to second Steve Lucas concern, especially as it applies to policy-makers. The current mentality – any way to rich predefined metric is good and cheap, not meeting target numbers is bad and expensive – is pervasive among not only doctors but also bureacrats who couldn’t say what NNT is or explain the difference between absolute risk and relative risk if their life depended on it. This is a link to an article from Clarian Health Plan that planned to penalize employees not only for smoking, but also for blood pressure, LDL, blood glucose being over predefined metrics: “At Clarian, employees who have blood pressure that’s above 140 over 90, blood glucose levels over 120, low-density lipoprotein cholesterol over 130, or a BMI over 29.9 could be subject to the paycheck deductions. “. Since a lot of people over 50 cannot achieve all of these metrics by just diet and exercize, the plan would push a lot of otherwise healthy people to take drugs. Never mind that in an individual case this could cause more harm than good. Never mind that it is likely to be a whole lot more expensive. I wonder what the idiots, sorry, policy-makers from Clarian can say after recent studies or even if they bother to read the evidence.

Policy-makers shall let doctors figure out how to treat sick people on an individual basis and using the best evidence available. But I am concerned that otherwise healthy people are constantly pressured to take drugs to reduce the very small risk of something bad happening future at the cost of quality of life today and maybe additional harms. Really, how many healthy people over 50 are out there nowadays?

http://www.dtu.ox.ac.uk/Slides/DTU_Slides005.ppt#257,2,Any Diabetes Related Endpoint

Slides showing fairly linear 21% decrease in mortality & complications down to A1c of <6.

I’m not arguing that everyone should shoot for <6. I’m saying that if you can get there without much effort, then you should. If you can get $500/month on Byetta, Actos, insulin etc. to get less than 7? No.

I give up. Keeps chopping out the middle of my comments.

dr. bob,

Your link to UKPDS 35 refers to an association study of sugars and outcomes. It showed that higher A1Cs are associated with worse health outcomes. We know and accept that. A1C is a marker of disease. Those with higher A1Cs have worse disease, which translates to worse outcomes.

The real question then becomes, what happens if we randomize diabetics and see if those that are pushed down to a lower A1C with drugs/insulin do any better. UKPDS answered that, if you read the links provided in previous posts, and showed that it doesn’t improve clinically meaningful outcomes. And ACCORD is confirming that. So treating the marker (A1C) doesn’t treat the underlying disease and doesn’t improve outcomes.

Here’s another BMJ link with a published letter in response to UKPDS 35 saying the same thing.

http://www.bmj.com/cgi/eletters/321/7258/405#9168

The Accord study is trying to tell us that NORMAL blood sugars are bad? Too many other studies that say normal is where we need to be.
If you understand diabetes and treatment options, there is no reason why anyone in the US should have blood sugars above an A1c of 5%, without having hypoglycemia.
Here is a comment from Dr. Richard K. Bernstein, Author of the best selling book, Diabetes Solution, Diabetes Diet and the audio CDset of The Secrets to Normal Blood Sugars at http://www.diabetes911.net

The question is really, was the claim made by the NIH that “lowering blood sugar actually increased the risk of death” a valid claim and if not, what was really going on? Well, what I maintain is that the problem was in the treatment, not in the fact that blood sugars were lowered. When this study was started, the ADA very clearly mandated 60% to 65% dietary carbohydrate for diabetics. This high carbohydrate diet forced the use of industrial doses of insulin, large doses of sulfonylurea drugs and very possibly at the very least a hazard for hypoglycemia; and a great likelihood of rollercoaster blood sugars as we usually see in diabetics who are put on a high carbohydrate diet. So it looks like the likely high carbohydrate diet was at the core of the problem. Now, aside from the impossibility of real blood sugar control and indeed, although the Gina Colata article in the New York Times claims that the blood sugars were very low. They weren’t. They did not get below 6% on the A1C.

Six percent corresponds to an average blood sugar of 140 mg/dL. So the blood sugars were still quite high. What hazards were introduced? Well, first of all, we know from a number of studies that high carbohydrate diets tend to increase rather than reduce cardiac risk factors. But in this case, probably much more significant was the likelihood of weight gain. We use low carbohydrate diets to reduce weight. So if you’re going to give them high carbohydrate diets and large doses of insulin to off set the resulting high blood sugars, you’re going to be building fat. And doing that to someone who’s already at high cardiac risk is just adding to their burden, probably adding tremendously. In addition, there’s been a lot written about the adverse effects of high serum insulin levels, principally, on the vasculature. For example, high serum insulin levels increase vascular leakage, cause pathologic proliferation of the vascular endothelium, arterial stiffening, and hypertension. In addition, the obesity also exacerbates hypertension. So if you’re making people fatter, you’re making their hypertension worse.

On the other hand, there have been articles pointing out that for insulin deficient individuals, if you put them on insulin, you facilitate vascular repair. So there’s a balance. Small physiologic blood levels of insulin help the vasculature whereas these industrial blood levels of insulin are harmful for the vasculature. So simultaneously, you’re increasing hypertension, you’re making them fat and you’re causing vascular damage in a number of different ways just from the high carbohydrate and the high insulin.

So the conclusion that the study should be terminated perhaps should have been replaced with a revamping of the study so that the treatment would be changed to mandate very low carbohydrate diets and physiologic instead of industrial doses of insulin. One other point to remember is that high doses of insulin combined with high carbohydrate cause the rollercoaster effect. If you take a type 2 diabetic who already has cardiac disease, and you put them on the rollercoaster blood sugars, up and down, and up and down, you’re not doing his heart any good.

A similar situation occurred in the DCCT trial in the intensive arm, more hypoglycemia. I wrote an article that was published in the American Journal of Medicine, after the DCCT. They were complaining that they had so much hypoglycemia, even at A1C’s of 6% and they didn’t get below 6%, but approaching 6% they got more and more severe hypos. I pointed out the laws of small numbers wherein high carbohydrate plus high insulin causes unpredictable blood sugars..

Items missing in the NIH press release included what sort of diet they were on and which oral medications they were using. I’d be very foolish if they were put on a low carbohydrate diet. I’m willing to bet that they were put on an ADA diet and it was probably very high in carbohydrate.
I am assuming that they used high doses of insulin and sulfonylureas because it’s very hard to offset carbohydrate with metformin, Actos® or Avandia®; whereas sulfonylureas, are almost as potent as insulin but they work by boosting your insulin levels. If you can make insulin and you get a sulfonylurea, you’ll have very high serum insulin levels.

Dr. Richard K. Bernstein is the Author of Diabetes Solution, http://www.diabetes911.net