High Carb T2 Diabetes Trial Ends in Failure

[borofergie]

NHS style High Carb / Low Calorie + Exercise Intervention fails, and study is abandoned after 11.5 years of a 13.5 year trial.
http://www.nytimes.com/2012/10/20/healt ... html?_r=2&

A large federal study of whether diet and weight loss can prevent heart attacks and strokes in overweight and obese people with Type 2 diabetes has ended two years ahead of schedule because the intensive program did not help.

The study randomly assigned 5,145 overweight or obese people with Type 2 diabetes to either a rigorous diet and exercise regimen or to sessions in which they got general health information. The diet involved 1,200 to 1,500 calories a day for those weighing less than 250 pounds and 1,500 to 1,800 calories a day for those weighing more. The exercise program was at least 175 minutes a week of moderate exercise.

But 11 years after the study began, researchers concluded it was futile to continue — the two groups had nearly identical rates of heart attacks, strokes and cardiovascular deaths.

Here is the diet:

The recommended diet is based on guidelines of the ADA and National Cholesterol Education program [96,97] and includes a maximum of 30% of total calories from total fat, a maximum of 10% of total calories from saturated fat, and a minimum of 15% of total calories from protein.

http://perfecthealthdiet.com/2012/10/lo ... -crossing/

So it's a 55% carbohydrate diet, exactly the sort of thing advocated by the NHS and DUK.

There is some speculation among bloggers that the trial was halted because more people died in the intervention group than in the usual care group:
http://high-fat-nutrition.blogspot.co.u ... opped.html

However the massive omission, from the quick look I've managed, is of any intention to report the all cause mortality. It seems very likely to me that more people died in the intervention group than in the usual care group, but p was > 0.05.

Call me a cynic, but I think they stopped the trial because they could see where that p number was heading. Has anyone seen a body count from anywhere in the trial?

This is more excellent evidence against the idiotic (diabetic killing) dietary advice handed out by the NHS and DUK. It demonstrates the inefficacy of both low-calore + exercise and high-carb as a method of treating T2 diabetes.

Also, what might the outcome have been if the intervention group had been repeatedly bullied, harassed and indoctrinated to maintain a normoglycaemic, low grade ketogenic diet for 13.5 years? Say to an HbA1c of around 5%?

Ha ha ha bloody ha.

http://high-fat-nutrition.blogspot.co.u ... opped.html

Happy days indeed.

 

[borofergie]

Better still, the results of this trial squarely show that obesity does not impair health, but that obesity is the result of impared health (or that something else cause obesity AND poor health).

Paul Jaminet's analysis:

We know that obesity is associated with poor health. Since causation implies correlation, the existence of this correlation suggests that either (1) obesity causes poor health, (2) poor health causes obesity, or (3) some third factors cause both obesity and poor health.

The Look AHEAD study presumed (1) – that obesity causes poor health. The “eat less, move more” intervention was wholly directed at weight loss. If obesity is the cause of poor health, Look AHEAD should have improved health. It didn’t. This tells us that the direction of causality is either (2) or (3). Obesity doesn’t impair health; other factors that impair health cause obesity.

 

[AlanC]

It seems like a terribly badly designed experiment to me. To be meaningful you should only vary one thing, but in the experiment says that dieting + exercise has the same effect as the medication. So three variables tied together (or four if you include the health education), which means that it is impossible to say which, if any, has any effect.

 

[borofergie]

It seems like a terribly badly designed experiment to me. To be meaningful you should only vary one thing, but in the experiment says that dieting + exercise has the same effect as the medication. So three variables tied together (or four if you include the health education), which means that it is impossible to say which, if any, has any effect.

True - but these three things are typically packaged together as the lifestyle improvements recommended to newly diagnosed diabetics. Eact of them (according to conventional wisdom) show help a little bit. The goal of the study was to demonstrate that these together these interventions would improve CV health outcomes for diabetics. The fact that these measures FAILED is demonstrative that the conventional advice is wrong.

What sucks about this study is that they pulled the plug when the results started to prove their hypothesis wrong. Instead of showing that outcomes were worse for patients on the high-carb / low-calorie / exercise NHS diet, they'll simply trying and make excuses about why their experiment was wrong.

 

[borofergie]

And here's the thing, we continually hear fear-mongering about "the dangers of long-term low-carb dieting" based on absolutely zero evidence, and here we have nailed on evidence that the NHS diet is only just about as good as doing nothing, and is probably worse.

I hope they publish the body counts.

 

[AlanC]

What sucks about this study is that they pulled the plug when the results started to prove their hypothesis wrong. Instead of showing that outcomes were worse for patients on the high-carb / low-calorie / exercise NHS diet, they'll simply trying and make excuses about why their experiment was wrong.

That is very cynical - there is no reason to suppose that the experimenters WANTED a particular outcome. Science works by making a hypothesis then testing it, and you accept the result regardless of whether or not the experiment confirms your hypothesis. In this case it didn't.

The experiment was stopped because it was clear that the two groups had virtually identical outcome, so there was no reason to continue. There is no reason to believe that continuing the experiment for the final 2 years would have shown a worse outcome for the exercise/diet group.

 

[GraceK]

And it ONLY took them 11 years? :roll:

 

[borofergie]

What sucks about this study is that they pulled the plug when the results started to prove their hypothesis wrong. Instead of showing that outcomes were worse for patients on the high-carb / low-calorie / exercise NHS diet, they'll simply trying and make excuses about why their experiment was wrong.

That is very cynical - there is no reason to suppose that the experimenters WANTED a particular outcome. Science works by making a hypothesis then testing it, and you accept the result regardless of whether or not the experiment confirms your hypothesis. In this case it didn't.

Eh, really? You do the experiment to prove your hypothesis (or to more accurately to disprove your null hypothesis), the whole point of the experimental design is to demonstrate that the proposed intervention is meaningful. If you fail to disprove your null hypothesis, then you have to accept it: this experiment demonstrates that the NHS / DUK / AHA guidelines are not effective in improving CV outcomes for the group of patients tested (obeses T2 diabetics).

If you don't think that the experimenters WANTED a particular outcome (because they thought that it would improve the health of the subjects) then the whole trial would be unethical. The protocol tested (and used in the diabetes centres) was invented by the lead investigator Reena WIng: http://biomed.brown.edu/facultydirector ... 1100925475

To suggest that she wanted to prove it wrong is a little strange don't you think?

“I was surprised,” said Rena Wing, the study’s chairwoman and a professor of psychiatry and human behavior at Brown University’s medical school.

Like many, she had assumed diet and exercise would help, in part because short-term studies had found that those strategies lowered blood sugar levels, blood pressure and cholesterol levels.

But, Dr. Wing added, “You do a study because you don’t know the answer.”

 

[borofergie]

The Look AHEAD (Action for Health in Diabetes) trial involved hundreds of doctors, nurses, dieticians and exercise therapists at 16 medical centers. It cost about $20 million a year, or about $220 million over its 11-year-life.

Just the $220 million then...

 

[AlanC]

Eh, really? You do the experiment to prove your hypothesis (or to more accurately to disprove your null hypothesis), the whole point of the experimental design is to demonstrate that the proposed intervention is meaningful. If you fail to disprove your null hypothesis, then you have to accept it: this experiment demonstrates that the NHS / DUK / AHA guidelines are not effective in improving CV outcomes for the group of patients tested (obeses T2 diabetics).

The experimenters apparently EXPECTED a certain outcome, and they hoped for a certain outcome, so they did the experiment to test the hypothesis, not to prove it. When the experiment gave an unexpected result they accepted the fact. I see nothing unacceptable with that.

It seems to me that the experiment is so badly flawed that it would be very hard to draw any solid conclusions from it. It is a huge waste of time and money. I doubt if the experiment will ever get published in a reputable journal because the design of the experiment is so poor, and so it will not get through peer review.

 

[Patch]

This might just be the beginning of a snowball...

 

[angieG]

The Look AHEAD (Action for Health in Diabetes) trial involved hundreds of doctors, nurses, dieticians and exercise therapists at 16 medical centers. It cost about $20 million a year, or about $220 million over its 11-year-life.

Just the $220 million then...

If they finished 2 years early at $20 million a year....would be good now if they used the remaining $40 million on giving test strips to those on low carb, high fat diets and see what the outcome of that is!!

Angie

 

[Dillinger]

The experimenters apparently EXPECTED a certain outcome, and they hoped for a certain outcome, so they did the experiment to test the hypothesis, not to prove it. When the experiment gave an unexpected result they accepted the fact. I see nothing unacceptable with that.

I don't think they accepted any facts; they dumped the trial before it was due to complete.

Isn't the issue that by terminating the trial 2 years before the due date then the results are now shelved; will the trial be published and reviewed if it's terminated? This smacks of 'tipping over the board' when you're losing at chess.

If the results are just dumped this just goes to show how incredibly difficult it is to change an accepted orthodoxy. Many of us know that there is an alternative to 'eat less/do more' and that it actually works, but even when actual evidence is provided that the orthodoxy doesn't make sense it is the evidence that gets canned and not the orthodoxy. The very same situation appears with statin trials; even where the fat/cholesterol/heart disease hypothesis is shown not to work by the very trials designed to prove it the response is to say 'well, everyone should take statins then'.

I think we're pretty much on our own here; we're off the map and our health care providers are just going to mutter about 'there be dragons' and 'falling off the edge of the world'; we've got to ignore them and make our own way, hoping we don't get eaten by cannibals (or paleos) like Captain Cook.

I take pleasure from this in a strange way; it is a vindication of what we are saying albeit one that will be struck out by those in power for technical purposes.

Best

Dillinger

 

[Patch]

I *kinda* take pleasure too - but not as much as i would have if the trial had run it's course and was properly published at it's conclusion.

Convention/orthodoxy is a hard thing to change...

This smacks of 'tipping over the board' when you're losing at chess.

Couldn't agree more - but in my house it was usually the Monopoly board that got launched into the air! :lol:

 

[phoenix]

What do we actually know?
At year eleven the trial was stopped. (this seems to be according to the procedure described in the protocol ;ie they described the circumstances that would stop the trial from the start(
This was during the follow up so by then very much reduced intervention.
there was no difference in CVD events
The 'lifestyle' (intervention) group used fewer medications than the DSE (control)group.
Overall in the lifestyle group there was a 5% reduction in weight.

What we don't know (though it's amazing how many people seem to think they can say what happened with zero information)
What was the drop-out level?... how many were attending the monthly sessions at the end?
Was there a difference in outcomes between those that continued to attend/ sustained larger amounts of weight loss and the drop-outs?
TBH until you know that then all speculation is useless

The experimenters apparently EXPECTED a certain outcome, and they hoped for a certain outcome, so they did the experiment to test the hypothesis, not to prove it. When the experiment gave an unexpected result they accepted the fact. I see nothing unacceptable with that.

It seems to me that the experiment is so badly flawed that it would be very hard to draw any solid conclusions from it. It is a huge waste of time and money. I doubt if the experiment will ever get published in a reputable journal because the design of the experiment is so poor, and so it will not get through peer review.

Why not?
They have already published interim results and a paper describing it's methodology.

This study grew out of the DIabetes Prevention Programme which seemed to show that a similar lifestyle intervention (weight loss and exercise could prevent or delay the development of diabetes in people at high risk.

Participants in the lifestyle intervention group-those receiving intensive individual counseling and motivational support on effective diet, exercise, and behavior modification-reduced their risk of developing diabetes by 58 percent This finding was true across all participating ethnic groups and for both men and women. Lifestyle changes worked particularly well for participants aged 60 and older, reducing their risk by 71 percent. About 5 percent of the lifestyle intervention group developed diabetes each year during the study period, compared with 11 percent of those in the placebo grou

.
http://diabetes.niddk.nih.gov/dm/pubs/p ... onprogram/

As one trial was a 'result' of the other the protocols. were similar but not identical.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2726971/
and
protocol for this trial
https://www.lookaheadtrial.org/public/L ... otocol.pdf

The researcher's were well aware that lots of short term studies show improvement in glycemic control and CVD markers (lipids etc) following weight loss but were also aware long term observational studies show mixed results (some show no difference/some improvement and a couple worse results) They discuss this in detail in the protocol publication.

This trial was to see if a long term intervention that focused on weight loss and fitness; similar to the intervention in the DPP could improve cardiovascular outcomes for those with T2 diabetes.


hypothesis

participation in an intensive multi-component weight loss intervention will reduce the risk of cardiovascular disease and improve other clinically important health outcomes.

Two arms:
An intensive lifestyle intervention (ILI) involving group and individual meetings to achieve and maintain weight loss through decreased caloric intake and increased physical activity was compared with a diabetes support and education (DSE) condition
The Group objective of the ILI group was
Mean loss > 7% of initial weight
compared to those assigned to the control group (Diabetes Support and Education).

The trial wan't about all those other factors that affect CVD.
All participants in both groups had the same HbA1c target, acess to blood glucose monitoring if on hypoglycaemic producing drugs , similar lipid targets/medication, blood pressure targets/medication, advice/help to stop smoking and advice on healthy diets
(so there was not an untreated control group(unethical!)
This might be important (John Buse in the NYT article suggests this)

published results
Year 1
ILI average 8.6% weight loss, DSE 0.7% weight loss
Fitness ILI improved 20.9 % DSE 5.8%
Greater proportion ILI reduced medications
Average HbA1c ILI 6.6% DSE 7.2%
Other measures, lipids,(including HDL and trigs) blood pressure, urine creatinine ratio improved significantly more in IDL than DSE.
Participants assigned to ILI lost an average 8.6% of their initial weight vs. 0.7% in DSE group (P < 0.001). Mean fitness increased in ILI by 20.9 vs. 5.8% in DSE (P < 0.001). A greater proportion of ILI participants had reductions in diabetes, hypertension, and lipid-lowering medicines. Mean A1C dropped from 7.3 to 6.6% in ILI (P < 0.001) vs. from 7.3 to 7.2% in DSE. Systolic and diastolic pressure, triglycerides, HDL cholesterol, and urine albumin-to-creatinine ratio improved significantly more in ILI than DSE participants ((all P < 0.01).
http://care.diabetesjournals.org/conten ... f_ipsecsha

This intensive support was reduced in year 2-4

By Year 4
those that were still 'on board' seem to have continued to reduce/maintain weight loss but this appears by then to be a minority

These results provide critical evidence that a comprehensive lifestyle intervention can induce clinically significant weight loss (i.e., ≥5%) in overweight/obese participants with type 2 diabetes and maintain this loss in more than 45% of patients at 4 years

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183129/

After this the support was again lowered so that after 4 years the lifestyle group had one session a month and the support group one session per year.

 

[Superchip]

Thanks borofergie, great post.
I've printed off two of the articles from the NY Times and shall present them to the DN at the next appointment fiasco.

Dillinger, excellent response, haha why let the truth get in the way of a damned good backhander ?

Regards

 

[borofergie]

It seems to me that the experiment is so badly flawed that it would be very hard to draw any solid conclusions from it. It is a huge waste of time and money. I doubt if the experiment will ever get published in a reputable journal because the design of the experiment is so poor, and so it will not get through peer review.

I don't accept it's flawed. It's testing the influence of the standard intervention recommeneded by organizations such as the ADA, NHS and DUK. I think that's a much better use of money than looking piecemeal at seperate interventions and then deciding that they don't all work together. Anyway, you could consider diet + exercise as a single intervention, set up to deliver a calorific deficit.

I think that we can derive some very solid conclusions from it:

“We were hoping that a weight-loss program would help reduce cardiovascular disease, but now we have the answer that it doesn’t,” said Mary E. Evans, a physician at the National Institute of Health’s National Institute of Diabetes and Digestive and Kidney Diseases, which paid for the study.

But the outcome is clear, said Dr. David Nathan, a principal investigator and director of the Diabetes Center at Massachusetts General Hospital. “We have to have an adult conversation about this,” he said. “This was a negative result.”

No-one spends $200m on a study and then fails to get it published in a peer reviewed journal.

 

[Patch]

But the outcome is clear, said Dr. David Nathan, a principal investigator and director of the Diabetes Center at Massachusetts General Hospital. “We have to have an adult conversation about this,” he said. “This was a negative result.”

This is a huge step forward.

 

[xyzzy]

So it's a 55% carbohydrate diet, exactly the sort of thing advocated by the NHS and DUK.

I dare say they'll now spend another $200m and take another 11 years to determine what could possibly have gone wrong with the parameters of the study and then do the same thing all over again rather than simply spot that number 55 as the cause.

The NHS DUK ADA etc have so much vested interest in making that high carb exercise message work they are certainly not going to undermine their own message as its the one that their political masters want to continue. It is far less damaging politically to blame "fat and lazy" people than actually accept the alternative and confront the real issues such as the leverage the food and drinks industry has over health policies world wide etc.

Despite feeling vindicated over my own personal low carb choices and the benefits I've seen ensue from making that choice I don't expect any changes will come of this anytime soon.

Anyone who is getting the starchy carb and exercise with every meal mantra form their doctors, dsn's and dietitians should print the conclusions out and take them to their next consultation as ammunition and ask them why they are being recommended to do things that have been shown not to work.

 

[borofergie]

What do we actually know?
At year eleven the trial was stopped. (this seems to be according to the procedure described in the protocol ;ie they described the circumstances that would stop the trial from the start(
This was during the follow up so by then very much reduced intervention.
there was no difference in CVD events
The 'lifestyle' (intervention) group used fewer medications than the DSE (control)group.
Overall in the lifestyle group there was a 5% reduction in weight.

What we know:

1. Moderate weight loss does not reduce cardiovascular disease.
2. An NHS style diet and exercise intervention does not improve mortality in T2 diabetics and the obese.

(1) alone is worth $200m. As Jaminet says, it points clearly to the fact that obesity does not cause health complications, but that obesity and health complications are both symptoms of a common third factor.
(2) Now that we've proved that high-carb/low-calorie+exercise doesn't work, we can go on to discussing other interventions that probably do work.


Reduced medications and weight-loss are very nice, but almost completely besides the point, if they don't improve outcomes, and they don't stop people dying then frankly, who gives a ****?

I'd put my diabetes into remission within weeks of being diagnosed, when I was still very obese (I still am technically obese). My weight dropped naturally as a result of my own low-carb intervention, which to me is a further illustration that obesity is a symptom, not a cause.

What we don't know (though it's amazing how many people seem to think they can say what happened with zero information)
What was the drop-out level?... how many were attending the monthly sessions at the end?
Was there a difference in outcomes between those that continued to attend/ sustained larger amounts of weight loss and the drop-outs?
TBH until you know that then all speculation is useless
[/quote]

It's all nice information, but it won't change the verdict:

“We were hoping that a weight-loss program would help reduce cardiovascular disease, but now we have the answer that it doesn’t,” said Mary E. Evans, a physician at the National Institute of Health’s National Institute of Diabetes and Digestive and Kidney Diseases, which paid for the study.

But the outcome is clear, said Dr. David Nathan, a principal investigator and director of the Diabetes Center at Massachusetts General Hospital. “We have to have an adult conversation about this,” he said. “This was a negative result.”

Time to move on, on the whole "50% carbs for diabetics" thing don't you think?