May 31, 2010

What the Health Media Missed: JAMA Study Quantifies Reporting Spin

If you have been reading this blog for a while, you know that from time to time I pick out some company funded study that has turned into a media sound bite promoting the company's product and read it to see what it really found. Almost always close reading of these studies finds statistical abuse so blatant that one concludes that the peer reviewers who approved it for publication flunked Statistics 101.

Now a study in JAMA quantifies just how bad this statistical abuse really is. The study is,

Reporting and Interpretation of Randomized Controlled Trials With Statistically Nonsignificant Results for Primary Outcomes. Isabelle Boutron et al. JAMA 2010;303(20):2058-2064.

A "statistically nonsignificant result" is one that could be due entirely to chance. If I test the proposition that a coin toss is more likely to come up heads by tossing a coin five times no combination of heads and tails that emerges from this "experiment" would be statistically meaningful. You have to toss that coin a lot more times to get a meaningful result because the same coin that would come up heads 50% of the time over 1,000 coin tosses may easily come up heads three or even four times when tossed only five times.

So what this JAMA study was examining was how researchers reported studies in which the hypothesis being tested came up with a statistically meaningless result, for example, a study that asks whether Drug X decreases the number of heart attacks in some population which finds that the change in the number of heart attacks in the study group could be entirely due to chance.

What the JAMA study found was that in 72 studies where the primary outcome resulted in a statistically nonsignificant result there was significant "spin."

Spin was defined thus:
...specific reporting strategies, whatever their motive, to highlight that the experimental treatment is beneficial, despite a statistically nonsignificant difference for the primary outcome, or to distract the reader from statistically nonsignificant results

In plain English, "spin" means claiming some treatment works when the statistics show it does not.

How frequent was spin? The JAMA Study finds:
The title was reported with spin in 13 articles (18.0%)

Spin was identified in the Results and Conclusions sections of the abstracts of 27 (37.5%) and 42 (58.3%) reports, respectively, with the conclusions of 17 (23.6%) focusing only on treatment effectiveness.

Spin was identified in the main-text Results, Discussion, and Conclusions sections of 21 (29.2%), 31 (43.1%), and 36 (50.0%) reports, respectively.

More than 40% of the reports had spin in at least 2 of these sections in the main text.
So no, I am not paranoid when I assert that peer reviewers approve the publication of studies that claim results where none occurred, based on ignorance of how statistics work.

Some of the ways I've seen this kind of spin deployed are to report a study as showing that results "trended" towards the desired outcome. In the case of our coin toss, the coin tossed five times that comes up heads three times "trends" towards heads. This is meaningless, since if you toss it 1,000 times it comes up 50% heads and 50% tails.

When a drug "trends" towards reducing heart attacks because 103 people who took the drug had heart attacks while 105 people who didn't take the drug had heart attacks, you have the identical meaningless finding. You would need to see a much bigger difference in outcomes to determine that the drug was effective when testing it in such a small group.

But using the "trend" argument is a very common way that drug companies and supplement companies suggest to the statistically ignorant (including the peer reviewers) that their product works when it doesn't.

This is why so many claims made for years about vitamins, supplements and new drugs turn out to be wrong when someone attempts to confirm the result with a large, statistically meaningful study.

Beyond mistating the study result, a common strategy for a company trying to spin gold out of dross is to misapply a statistical technique to the meaningless result that amplifies it into a number that appears, to those who don't understand the GIGO principle, to be meaningful.

When there is a statistically meaningless finding for incidence of heart attack, use the inflationary measure, "risk of heart attack," and if that still doesn't give you a meaningful statistic, try measuring "change in risk." If risk (already a statistical amplification of incidence) drops a meaningless 2% in the drug group and 1% in the placebo group, we have a 50% "change in risk." That sounds very impressive to the math-flunkees who decide which studies get published, because I keep seeing just that kind of statistical slight of hand being used. But it is meaningless, because since the difference in incidence could be entirely due to chance and come out the other way if the study was repeated again any statistic derived from incidence is statistically meaningless, too.

This doesn't even get into the related issue that drug companies falsify results or run "controlled trials" where the two groups under study are not well matched. If you compare a sicker older placeo group to a younger healthier group who take a drug, your drug may look effective when it isn't.

And then, there is the issue of "controlling" for various cofactors. The notorious ACCORD study, long interpreted as meaning that tight control killed people with diabetes ignored the fact that the people in the tight control group who experienced bad outcomes did not, in fact, have tight control. There were more people with bad control in the "tight control" group than in the control group, so the slight increase in bad outcomes in that "tight control" group had nothing to do with tight control but was instead due to LACK of tight control.

Sadly hundreds of thousands of people with diabetes have been told by now that "tight control" is dangerous and that they should maintain A1cs of 7%, not 6% to be "safe." It will take years to undo the damage because busy health professionals don't have time to read all the health news and the debunking of ACCORD did not get the press that the original study received.

BOTTOM LINE: Your health and safety is being severely compromised by the peer reviewers who rubber stamp publication of company sponsored research that pretend that statistically meaningless results have meaning. The people who pay for this deceit and stupidity are the patients who end up taking expensive, dangerous, and worthless drugs.

Sadly, in a society that remains mostly math-illiterate, this isn't going to change any time soon.

May 11, 2010

Understanding Fasting Blood Sugar

Among the most common questions people have about Type 2 diabetes is this: how can they lower their fasting blood sugar?

To answer this question in a way that will help you lower your blood sugar we are going to have to first explain why doctors measure fasting blood sugar and what it does--and does not--tell us about our blood sugar health.


Traditionally, fasting blood sugar is the value you get when you test your blood sugar after an 8 hour long fast--which is usually immediately upon waking. In a normal person this fasting blood sugar would also be the "baseline" blood sugar--the level to which blood sugar returns a few hours after every meal all day long.

However, for reasons we will discuss later on, this is often NOT the case for people with Type 2 diabetes, whose morning blood sugars may be much higher than the baseline level they achieve after meals for the rest of the day.

Doctors have for decades relied on the FPG (fasting plasma glucose) test which measures fasting blood sugar to diagnose diabetes. The reason for this is NOT that FPG test results predict diabetic complications. They don't. Post-meal blood sugar tests are a much better indicator of whether a person will get the classic diabetic complications, and the A1c test is a better indicator of potential heart disease.

But the FPG test is cheap and easy to administer, hence its popularity.

The value most of us would find much more helpful in assessing our health is not fasting blood sugar but something else: the number of hours a day our blood sugar spends elevated over the level known to cause complications, which is roughly 140 mg/dl (7.7 mmol/L).

A person can wake up with a FPG of 130 mg/dl (7.2 mmol/L), but if it drops after breakfast and most hours of the day are spent with blood sugars that remain under 120 mg/dl, the person can expect years of complication-free living.

In contrast, a person may wake with a normal FPG of 98 mg/dl (5.4 mmol/L) but end up spending the next 14 hours with blood sugars well over 170 mg/dl (9.4 mmol/L). That person is seriously at risk for heart disease, diabetic nerve damage, kidney damage, and retina damage.

So when you assess your own fasting blood sugar, the question you want to ask is this: How many hours a day am I spending with my blood sugar in the range that causes complications? Not, necessarily, how can I lower my fasting blood sugar?

Obviously, if your fasting blood sugar is over 140 mg/dl (7.7 mmol/L) and goes up after each meal, you are going to be spending many hours a day in the danger zone and lowering your fasting blood sugar does become a huge issue. Fortunately, it is also one that can be solved.


Several independent factors can raise fasting blood sugar, and if you have a problem with it, the reason for your problem may NOT be the same as the reason for another person's even if they get the identical blood test results that you get.

Here are common reasons for high fasting blood sugar.

1. High post meal blood sugars. Your beta cells can only make so much insulin. If you elevate your blood sugars severely by eating more carbohydrate than your body can handle, your body will spend the whole night using what insulin it can manufacture to mop up the glucose that is still circulating thanks to those high carb meals.

Many people with diabetes cannot handle more than 12-20 grams of carbohydrate at a single meal, no matter what you might have been told by doctors or dietitians. Many of us will find that if we drop our carbohydrate intake dramatically, our fasting blood sugar plummets equally dramatically. It may take as little as two weeks of restricted carbohydrate intake to see fasting blood sugars revert to normal.

You can use this technique to lower your fasting blood sugar. It has worked for literally thousands of people:

How to Get Your Blood Sugar Under Control

2. Damaged Basal Insulin Secretion. The body secretes insulin in two different physiological processes which are described on this page: How Blood Sugar Control Works--And How It Stops Working. I urge you to read this page because mastering the concepts it explains will greatly help you understand and manage your diabetes.

Basal insulin secretion takes place throughout the day without reference to what you eat. Tiny amounts of insulin are squirted into the blood stream in small pulses every few minutes. However, sometimes things go wrong with the factors that control basal secretion. If that happens, your body may still be able to secrete insulin in response to meal time rises in glucose, but you lose the ability to secrete those tiny pulsing bursts. This can cause a rise in fasting glucose that can not be corrected with dietary changes. If you have this problem, you might need a basal insulin--a slow acting insulin that mimics the effect of natural basal secretion.

Basal failure is relatively rare, but when it happens you often find people with high fasting blood sugars whose blood sugar normalizes as soon as they eat and stays normal until they have metabolized their last meal. There are also genetic forms of diabetes (GCK mutations) that will cause elevated fasting glucose, however, this will be a lifelong problem, not one that comes on with age.

3. Dawn Phenomenon. If your blood sugar is highest first thing in the morning, and normalizes after you eat or exercise and stays normal hours after dinner, you may have a disturbance of regulatory hormones that is called "dawn phenomenon."

Our bodies prepare for waking up by secreting stimulating hormones shortly before dawn. These increase our insulin resistance in order to raise blood sugar a small amount. If we were animals who had to go hunt for our first meal, that excess glucose would be useful. Since were are people with refrigerators, it is less so.

Everyone experiences this early morning hormone burst, but in people with diabetes it can become highly exaggerated. In some people it is resistant to any treatment, but once the person goes about their day and eats, the blood sugars become more controllable.

If you have dawn phenomenon that doesn't respond to various lowering techniques, don't panic. As long as you are spending most of the day with your blood sugars at a safe level (Always under 140 mg/dl and under 120 mg/dl as much as possible) you'll be fine.

4. Too Much Injected Insulin or Oral Insulin-Provoking Drug. This is counter-intuitive, but common. If you are using a basal insulin (Lantus or Levemir) there is a temptation to use a lot of it to try to lower post meal blood sugars. Your sugars will be pretty good as long as you keep eating carbs, but once you stop eating at night, the insulin keeps being absorbed into your blood stream and by 3 AM it is quite common to hypo.

However, many of us as soon as we hypo slightly, experience a burst of counterregulatory hormone intended to push the blood sugar back up to normal so by the time you wake your blood sugar is high, not low. You can tell if you have had a counterregulatory burst because it will often wake you up at 3 AM with a jolt. Your pulse will be fast and your blood pressure may be elevated too. If you measure your blood sugar it won't be low, because as soon as you get that jolt, your blood sugar will surge. That's what the jolt is meant to do.

If you are waking at 3 or 4 AM and end up with high fasting blood sugars, cutting back on your Lantus or Levemir may solve the problem. Lantus and Levemir are NOT meant to cover the carbohydrates you eat at meals, only to lower your baseline blood sugars. If you need insulin to control meals, you need to ask your doctor for fast acting insulin and the diabetes education it requires to learn how to use it correctly.

Glipizide and Amaryl (glimepiride) can also cause this problem as they cause long lasting insulin secretion in people who are sensitive to them.

5. Too Much Blood Pressure Medication. Too much blood pressure medication will also cause an early morning counterregulatory attack because if your blood pressure drops too low, you will get a burst of epinephrine and other hormones meant to keep you alive. It will raise both blood pressure and blood sugar.

I experienced this myself and since posting about it on my blog have received emails from others who experienced this same phenomenon. It is most likely if your blood pressure medication is giving you low normal readings during the day--90/60 for example, or if you experience postural hypotension attacks where you black out when you bend over.


Here are some of the things people report helped them. They are worth a try.

1. Cut way back on your meal-time carbohydrate intake.

2. Drink a glass of wine with dinner or before bedtime. One is enough. The alcohol can inhibit the liver from dumping glucose.

3. Eat a protein snack before bedtime.

4. Change the time of day when you take your medications. Metformin ER taken at bedtime will have a stronger impact on fasting blood sugar than the same pill taken in the morning. However, you may see higher post meal values if you change the timing. Remember your goal is maximum hours of lower blood sugar, not one low reading in the morning.

5. Split Lantus or Levemir doses so you take half in the morning and half in the evening. Lantus does not last 24 hours in many people, especially when taken in small doses (12-30 units) so if you take it in the morning it may be gone by 3 AM. Splitting the dose may give you better coverage. Discuss this with your doctor before you make changes, especially if you haven't been taught how to adjust your insulin doses. DO NOT MODIFY YOUR INSULIN DOSES IF YOU DON'T UNDERSTAND HOW THEY WERE SET!

6. Metformin. If you aren't taking metformin, ask your doctor about it. It is the most appropriate drug for controlling fasting blood sugars because it can sometimes block the liver dumping that raises blood sugar in response to dawn phenomenon hormones.

May 5, 2010

ACCORD Redux: It's the High Blood Sugars, Stupid!

The ACCORD study has been used to justify the imbecilic idea that lowering blood sugar is dangerous to people with diabetes. ACCORD was a very large study in which one group of people with diabetes were given a strong cocktail of diabetes drugs with the aim of lowering their A1c below 6.0. Those drugs included sulfonylureas, Avandia and Actos, all drugs known to increase heart problems. The other group of study participants kept their A1cs in 7% or higher range recommended by the ADA. The result was that the group of people shooting for the lower A1cs had slightly more heart attacks than those maintaining mediocre control.

For perspective, it is worth noting that another larger study, ADVANCE, pursued the same strategy with different drugs and found NO excess deaths in the tight control group.

And in both studies, the group with tight control had less classic diabetes complications most notably neuropathy and kidney disease.

But because of that small number of excess deaths in the tight control arm of ACCORD, many family doctors are now telling patients that lowering blood sugar is dangerous. Fortunately, a new study of the ACCORD data puts this into perspective.

The study is:

Epidemiologic Relationships Between A1C and All-Cause Mortality During a Median 3.4-Year Follow-up of Glycemic Treatment in the ACCORD Trial. Matthew C. Riddle et al. Diabetes CareMay 2010 vol. 33 no. 5 983-990. doi: 10.2337/dc09-1278

This study found,
...a higher average on-treatment A1C was a stronger predictor of mortality than the A1C for the last interval of follow-up or the decrease of A1C in the first year. Higher average A1C was associated with greater risk of death. [emphasis mine]

These analyses implicate factors associated with persisting higher A1C levels, rather than low A1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.

It doesn't get any simpler than that. It doesn't matter how much you lower A1c if you keep blood sugar higher than the level at which complications and heart attack ensue.

In addition, A1c is a poor indicator of post meal blood sugar, so it is possible to lower A1c without eliminating the blood sugar spikes over 160 mg/dl that we know are associated with a huge increase in cardiovascular risk. Details HERE.

If your doctor tries to discourage you from lowering your blood sugar, find a new doctor.

Careful, thoughtful analysis of the data from ACCORD and the Veterans Study which have been used to support the idea that lowering blood sugar is dangerous have really only proven the following:

1. Not lowering blood sugar enough to prevent organ damage kills people. You can read what peer reviewed research has learned about what blood sugar levels are associated with organ damage HERE. You can learn about what peer reviewed research has found about what blood sugar levels are associated with heart disease HERE.

2. Lowering blood sugar using dangerous oral drugs may slightly increase mortality. Avandia and Actos both raise the risk of heart failure in people who did not have it to start with. Some sulfonylurea drugs are associated with elevated heart disease risk. Details HERE and HERE.

3. Lowering blood sugar in elderly subjects only after they have gone through decades of terrible control and irretrievably damaged their hearts and other organs isn't very helpful but lowering blood sugar starting at diagnosis provides major long lasting health benefits. Details HERE.

4. Lowering blood sugar using a low carb diet is safe and effective and eliminates the threat of hypo and the potentially fatal side effects of oral drugs that only emerge after people take them for a decade or more. Details HERE. Even the ultra-conservative ADA, funded mostly by drug and junk food companies who lose profits when people with diabetes eat a low carb diet has had to admit this.

The problem with oral drugs is that they act on cell receptors that though they lower blood sugar also do OTHER things elsewhere in the body. Sulfonylureas stimulate receptors on the heart, not just the pancreas. TZDs convert bone stem cells into fat cells, leading to serious osteoporosis, long term. Januvia and Onglyza inhibit DPP-4 which is used elsewhere by the immune system to fight melanoma, ovarian cancer, prostate cancer and lung cancer.

Lowering blood sugar by eliminating as much carbohydrate as possible and if that doesn't provide normal blood sugars supplementing diet with the safest drugs: Insulin and metformin will provide major health benefits and keep you alive and healthy. And the sooner you start normalizing blood sugar after diagnosis, the more benefit you'll reap.