Thursday, February 07, 2008

ACCORD Trial Mess

From the New York Times,

...a major federal study of more than 10,000 middle-aged and older people with Type 2 diabetes has found that lowering blood sugar actually increased their risk of death, researchers reported Wednesday.

It's hard to make heads or tails of what happened as the actual data has not been released - we're left to read through press reports and information provided by the NIH to try to determine what went wrong in the trial. Everyone seems to be bending over backward to get the message across that the intensive drug therapy - a large number of pharamaceuticals taken together - had nothing to do with the higher incidence of death in the trial.

But one must really wonder!

Speculation abounds, but that hasn't stopped some from foisting out the idea that it is the lowering of blood sugars to normal ranges that was the problem, not the means utilized to do it.

Dr. Irl Hirsch, a diabetes researcher at the University of Washington, said the study’s results would be hard to explain to some patients who have spent years and made an enormous effort, through diet and medication, getting and keeping their blood sugar down.

They will not want to relax their vigilance, he said.“It will be similar to what many women felt when they heard the news about estrogen,” Dr. Hirsch said. “Telling these patients to get their blood sugar up will be very difficult.”

Call me crazy, but didn't this study throw every pharmacuetical intervention at these folks?

Perhaps the problem wasn't the lowered blood sugars, but toxicity and side-effects from massive drug therapy to acheive a lower blood sugar level?

“Many were taking four or five shots of insulin a day,” he said. “Some were using insulin pumps. Some were monitoring their blood sugar seven or eight times a day.”

They also took pills to lower their blood sugar, in addition to the pills they took for other medical conditions and to lower their blood pressure and cholesterol. They also came to a medical clinic every two months and had frequent telephone conversations with clinic staff.

What this trial lacked was a control group utilizing an effective, non-pharmaceutical approach - a carbohydrate restricted diet - to lower blood sugars and A1c, which would have resulted in less medication, not more to achieve glycemic control.

If and when the data is published, I'll update - but for now think it highly irresponsible of anyone to speculate that it was simply the lowering of blood sugars that caused the problem given the wide variety and large number of medications used to intensively reduce blood sugars; and worse is to suggest that those with type 2 raise their blood glucose levels!

17 comments:

  1. squarecube11:55 AM

    Because regular readers of your blog have read The Great Cholesterol Con by Malcolm Kendrick, the answer is a little more obvious to us than it is to them.

    The paper said most of these deaths are from heart attacks. Do you remember Ken Lay and Enron. Do you think he was under any stress as he awaited sentencing?

    I've only just started measuring glucose levels this year and I have found it a very, very frustrating business. Fail, fail, and fail again and the worse readings are in the am. Hmmm

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  2. Anonymous1:01 PM

    I thought of the stress idea too, but I'm wondering if it maybe it was all that insulin they were shooting up with. (Thinking back on Taubes here, of course). Can't wait to see how they explain away this one.

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  3. They were urged to eat the high carb diet. They were put not only on drugs for blood sugar but on perhaps several blood pressure drugs AND a combination of a statin and a fibrate.

    There is no way with that many drugs involved that any analysis could figure out which drug interaction was causing the problems. But you better believe it would be drug interactions.

    Insulin is the most benign of all the drugs used in the study, but it was probably given WITH Avandia or Actos which is a toxic combination for the heart.

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  4. I'm not so sure insulin WAS the most benign drug here.

    Consider, as T2 diabetics they were most likely hyperinsulinemic already. Then, they're eating 'low-fat high carb' but covering the hell out of it with insulin.

    Unless I mis-read the literature, high levels of insulin are strongly associated with CVD.

    It may be -- and I'm guessing since I don't have the data -- that these people has astronomical levels of insulin in the system, trying to keep blood glucose tightly controlled with a high-carb diet.

    I'd bet on the insulin overdose as the culprit here.

    How could lowering BG to 'near normal' be somehow fatal?

    There's a disconnect there somewhere.

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  5. Anonymous5:07 PM

    I suspect the multiple drug cocktail scenario as a cause is a good first guess. My wife, an R.N., tells me that many Type 2 diabetics need to maintain their blood sugar levels above the normal level. When drugs take their levels down to what is "normal" for healthy people, they often start suffering. At least that is how I understood her comments which comes from her experience in a hospital.

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  6. I look forward to an update when the data is published. If I was a type 2 diabetic there is no way I would be raising my blood sugar levels as suggested by the study authors - that's just ridiculous!!

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  7. Anonymous9:19 PM

    To state that this study shows that diabetics should strive for higher blood sugars is ludicrous. What it really suggests, of course, is that current nutritional and/or pharmacologic therapy for type 2 diabetes may, on balance, do more harm than good. When these treatments are applied more intensively, the harm becomes more readily apparent, an interesting dose-response effect that should provoke a rethinking of the entire treatment paradigm. It's long past time to abandon the notion that the goal of treatment should be to maintain blood sugar, blood pressure, HDL, LDL, etc. within target ranges. Nonsense! Unless a specific treatment regimen has been shown to reduce mortality and morbidity, and to improve quality of life (or at least not degrade it) it should be viewed with skepticism and concern for the law of unintended consequences.

    ACCORD is a good example of what can happen when treatment is aimed at lab values and risk factors rather than at the fundamental disease process itself. (I'm reminded of torcetrapib, rosiglitazone, and ezetimibe here.) Insulin resistance is a defense mechanism against excessive insulin signaling. It should come as no surprise that using polypharmacy to defeat the defense mechanism may make matters worse.

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  8. "My wife, an R.N., tells me that many Type 2 diabetics need to maintain their blood sugar levels above the normal level."

    Back when the only choices were diet, insulin and a few oral meds, the goal was always to get patients as near normal as possible. The result? Less complications.....complications that are not only common, but expected today.

    Back then (1976 diploma grad) we could predict which patients were going to do well and which were going to get complications, simply by looking at their blood sugar control. And back then, we went by glucose spilling into the urine, which means blood sugars were very high. (People tested their urine at least 4 times daily, looking for glucose and ketones. When the blood glucose level exceeds the renal threshold of 180, glucose is excreted in the urine)

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  9. It might be the drugs, or it might be the carbs all by themselves. Isn't there at least some theory that glycosylation is responsible for damage to coronary arteries? And if you're taking a lot of oral hypoglycemics and insulin, might you not feel that you can eat more carbs than someone who is taking less medication?

    I wrote my take on this on my blog:

    http://migraineur.wordpress.com/2008/02/08/breaking-news/

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  10. Oh! I just noticed that the author of the article is Gina Kolata. I think a third-grader knows more science than Gina does.

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  11. Because regular readers of your blog have read The Great Cholesterol Con by Malcolm Kendrick, the answer is a little more obvious to us than it is to them.

    On the stress track:


    From the ACCORD team, Dr. John Buse:

    "The patients enrolled in this study were quite vulnerable in that they were relatively old (average age 62) and had heart disease or at least two or more other risk factors for heart disease. Maybe we just flogged them too hard to get their sugar levels down. The intensive group had extremely rigorous treatment, with some patients taking four shots of insulin and three pills and checking their blood-sugar levels four times a day. Perhaps this was just too many drugs at too high a dosage, and the effort required just stressed them out too much. I think our conclusion is therefore that we should not be zealots about lowering blood sugar at all costs.

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  12. Anonymous11:48 AM

    i think the ischemic preconditioning is envolved in this issue.
    Oral hypoglycemic agents can abolish the ischemic preconditioning and induce higher mortality rates.

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  13. It would be interesting to know the incidence of hypoglycemia in the intensively treated arm vs the standard group. Apart from neurologic complications like strokes hypoglycemia affects the myocardium too....

    http://www.ncbi.nlm.nih.gov/pubmed/16787671?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum

    ...I guess starving the heart of its main energy source (glucose) produces the same effects as ischemia....

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  14. The patients enrolled in this study were quite vulnerable in that they were relatively old (average age 62) and had heart disease or at least two or more other risk factors for heart disease.High blood pressure cure supplement, natural herbal remedy to lower & control high blood pressure. Use Alistrol everyday to help maintain healthy circulation and support cardio-vascular health.

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  15. I look forward to an update when the data is published. If I was a type 2 diabetic there is no way I would be raising my blood sugar levels as suggested by the study authors - that's just ridiculous!!

    It might be the drugs, or it might be the carbs all by themselves. I wrote an update on my blog

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  16. Anonymous3:59 PM

    Great piece of writing along with truly useful ideas. Appreciation for putting this together.

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  17. Anonymous2:37 AM

    The most effective posts I've ever checked out with this topic. Thanks!

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