Before I review this week’s study, bear with me while I clear up some terms.

Type 1 diabetes mellitus and type 2 diabetes mellitus are completely different diseases.  That they have such similar names and are differentiated only by a “type” promotes the common misunderstanding that they are subtypes of the same disease.  They should just have different names to keep things clear.  (I suggest “George” and “Bob”.)  They have entirely different causes and treatments.  Type 1 diabetes is caused by the body’s immune system destroying the pancreas’s ability to make insulin, the hormone that controls blood sugar levels.  It tends to be diagnosed in children and young adults.  Insulin is entirely absent in these patients, so insulin is the only treatment.

Type 2 diabetes is caused by hormonal changes that prevent insulin from working well.  It is usually diagnosed in overweight adults.  Treatments include weight loss, a low carbohydrate diet, and various medications that lower blood sugar, including insulin.  Type 2 diabetes is over ten times more common than type 1, and when people just say “diabetes” they mean “type 2 diabetes mellitus”.  Some type 1 patients are justifiably cranky at the public misunderstanding of their disease and at being lumped in with the greater number of type 2 patients.  The only things the diseases have in common are elevated blood sugar and the complications that result from that.  (The word diabetes derives from an ancient Greek term relating to a frequent symptom of elevated blood sugar – excessive amounts of urine.  This is also a symptom of a third entirely unrelated disease, diabetes insipidus, which should absolutely have a completely different name, like “Fred”.)

Are you with me so far?

Well, this week’s post is about type 1 diabetes.  A major struggle in type 1 is keeping blood glucoses as close to normal as possible, while avoiding hypoglycemia (abnormally low blood sugar).  The standard of care for a long time has been multiple daily blood sugar measurements and insulin injections.  More recently, insulin pumps have become available which infuse insulin continuously in an attempt to more accurately match the normal function of the pancreas.  The most recent advance has been continuous glucose monitoring, in which a sensor displays ongoing data about the glucose level and its trend over time.

A study this week in the New England Journal of Medicine compared glucose control in child and adult type 1 patients randomized to multiple daily insulin injections versus an insulin pump with continuous glucose monitoring.  The group with the insulin pumps achieved lower average blood sugars without an increase in hypoglycemia.

This advance offers the potential of minimizing the serious complications of type 1 diabetes, and will likely become the standard of care for motivated patients who can learn the intricacies of insulin pump use.  The long-term goal of an artificial pancreas – an insulin pump integrated with a glucose sensor that adjusts insulin doses automatically – is now one step closer.

Learn more:

Wall Street Journal article:  Medtronic Insulin Pump Shown To Work Better Vs Injections

New England Journal of Medicine article:  Effectiveness of Sensor-Augmented Insulin-Pump Therapy in Type 1 Diabetes

New England Journal of Medicine editorial:  Continuous Glucose Monitoring — Coming of Age

My regular readers know my skepticism about vitamin supplements.  I leap at the chance to bring you news that some vitamin has been tested for some disease and found useless.  So for balance, I have to also report when a well-designed study finds that a vitamin actually helps something.

This week’s New England Journal of medicine published a study about the treatment of nonalcoholic steatohepatitis (NASH).  NASH, also known informally as fatty liver, is a condition in which fat is deposited in the liver, causing liver inflammation.  It is more common in overweight patients, and those with diabetes and elevated triglycerides.  Fatty liver may eventually progress to liver failure.

Weight loss is the mainstay of treatment for fatty liver, and though some medications have been used for NASH, none have been proven to be effective.

The study randomized patients with fatty liver to placebo or 800 IU of vitamin E daily.  (There was a third group randomized to Actos, a diabetes medication, but that’s for another post.)  The patients were followed for about two years.  Improvement in their fatty liver was assessed by liver biopsy at the beginning and end of the study.

The patients taking vitamin E did quite a bit better than the patients taking placebo, with significantly more of the vitamin E patients having improvement or resolution of their fatty liver.  The authors of the study caution that the trial was too short to test the long-term safety of vitamin E, especially at this high dose.  They cite a worrisome study from 2005 that suggests that vitamin E at high doses may actually be associated with higher mortality.  (See second article, below.)

So if you have NASH talk to your doctor about starting vitamin E, and keep working on losing weight.  If you don’t have NASH and are taking vitamin E, consider donating your vitamin E to someone with NASH and taking a daily dose of nothing.

Learn more:

New England Journal of Medicine article: Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis

Annals of Internal Medicine Articles:  Meta-Analysis: High-Dosage Vitamin E Supplementation May Increase All-Cause Mortality

Few things captivate the public more than a new diet.  From Atkins to Ornish to the Mediterranean diet, each new theory attracts attention and true-believer adherents and generates lots of book sales and interviews on daytime TV.  People passionately argue about whether a diet low in carbohydrates or low in fat is best for weight loss.  But until now no large trial has ever been done to answer the question.

This week’s New England Journal of Medicine published the largest study that directly compares different diets to measure which yields the greatest weight loss.  Over 800 overweight adults were randomized to one of four different diets.  (Importantly, diabetics were excluded.)  They were all given diets calculated to provide 750 calories fewer than they were burning daily, but the four diets differed in the percentage of calories from fat, protein, and carbohydrates.  Two of the diets were low-fat and two were high-fat.  Two were average-protein and two high-protein.  And the four diets provided a broad range of carbohydrate intake from low to high.

The participants were also asked to participate in periodic group counseling sessions and were instructed to do 90 minutes of moderate exercise per week.  They were followed for 2 years and their compliance with group attendance, diet and exercise was tracked.

Interestingly, the four diet groups lost weight at the same rate.  Six months into the study the participants lost an average of 13 lb, 7% of their body weight.  After that, on average, they slowly regained weight, so that by two years the average weight loss was 9 lb, the same in all four groups.

So diet and exercise lead to weight loss, and whichever low-calorie diet you can stick to is as good as any other.  So get started.  You can still buy the latest diet book and swear that it’s the best because your favorite actor lost weight on it.  Only you and I will know that you owe your success to the New England Journal of Medicine.

Learn more:

New England Journal of Medicine article:  Comparison of Weight-Loss Diets with Different Compositions of Fat, Protein, and Carbohydrates

NY Times article:  Study Zeroes In on Calories, Not Diet, for Loss

For the hundreds of thousands of Americans whose kidneys have stopped functioning, there are two options: lifelong dialysis or kidney transplantation.  Dialysis is time consuming, carries serious risks, and only partially replaces the functions of a healthy kidney.  Patients live longer and have a much better quality of life after receiving a kidney transplant.  The difficulty with transplantation is that donated organs are scarce and transplants are more likely to be successful with living donors than with recently deceased donors.

Physicians and potential donors have been concerned about the health risks involved in kidney donation.  Besides the short-term risk of the surgery, there was a concern that kidney donation over subsequent decades would lead to all the bad consequences of other kinds of kidney injury: high blood pressure, worsening kidney function, eventual kidney failure, and shorter life span.

Because of that, potential kidney donors have to go through a meticulous screening process.  Anyone with any risk factors for developing kidney disease later in life is excluded.  So no one donates if he has diabetes, high blood pressure, protein in the urine (an early sign of kidney disease) or decreased kidney function.

Because of these precautions, it’s been assumed that kidney donors do well after donation and live a normal life, but this has never been actually studied in a large number of donors.  There were also worrisome reports of a few kidney donors who eventually lost all kidney function and needed dialysis themselves.  Was this a consequence of their donation or a random event that would have happened anyway?

A large study in this week’s New England Journal of Medicine attempted to answer the question.  It followed the health, kidney function, and quality of life of thousands of kidney donors and compared them to people in the general population who had the same age, sex and race as each donor.  The results were that the donors had the same longevity, general health, and better kidney function than the general population.  And they have excellent quality of life, on average.  This was trumpeted in the general press as great news for kidney donors.

Not so fast.  I think that this is a perfect example of why it’s important, when possible, to read the original article rather than rely on a newspaper science reporter to filter information for you.  The results are not nearly as heartening as reported.  Remember, all the kidney donors were very carefully screened before being allowed to donate.  So as a group they were much healthier then the general population.  They were then compared with the general population and found that their health and lifespan is no worse.  That’s not good; they should have done much better.  Headlines declared that kidney donors have normal life spans, but before their donation they should have had better than normal life spans.  That’s not a reassuring bit of news about kidney donation.

The authors of the study are very forthright about this important limitation to their findings, but you only find that out if you read their discussion in the original article.

Studies that more accurately determine the long term risk of kidney donation are currently ongoing.  In the meantime, potential donors should not take false comfort from this study.

Learn more:

New England Journal of Medicine article: Long-Term Consequences of Kidney Donation

Los Angeles Times article:  Kidney donors have a normal life span, study finds

Many people use the occasion of the New Year to reflect on the last year and make specific goals for the next.  Resolutions can be very helpful motivators if they are specific, realistic and written down.  Just as people make goals for their careers and their relationships, resolutions for your health are a smart way to work for achievable targets in the health-related struggles you face.

So I encourage you this week to write down your health resolutions for 2009.  Obviously, what progress is achievable is as varied as the people making resolutions.  An elderly lady with balance problems may resolve to attend physical therapy and use her walker consistently and have an entire year without falling.  A younger more active woman may resolve to train for and compete in a triathlon.  There is no objective marker for your goals.  You just have to balance ambition with realism.

My suggestion is to make the resolutions as specific as possible.  Detailed planning will help overcome procrastination and a specific goal will keep you accountable.  So don’t write

• I’m going to exercise more
• I’m going to eat less
• I’m going to lose weight

but instead write something like

• I’m going to walk for 45 minutes Monday through Friday before work
• I’m going to join Weight Watchers and attend meetings weekly
• I’m going to weigh 205 lb on January 1, 2010

If you have diabetes, you should be following your glycated hemoglobin (or hemoglobin A1C).  Write down a goal for it.  If you’re struggling with your cholesterol, pick a goal for your LDL.  If your blood pressure is too high, write down something like

• My blood pressure will be lower than 140/90 on every doctor visit

If you’re smoking, 2009 is the perfect year to quit (on a specific date that you should pick now).  Obviously, some of these goals may require your physician’s help in terms of adjusting your medications, but your doctor can’t do it alone.

Making yourself accountable to others can also help keep you on track.  Give a copy of your resolutions to your spouse, to your doctor to attach to your chart, to anyone who knows you too well and cares for you too much to let you cheat yourself.

I wish us all a year of peace, health, prosperity and happiness.

“If you think health care is expensive now, wait until you see what it costs when it’s free.”
– P.J. O’Rourke

I’ve written several times about the proven benefits of a family of cholesterol-lowering medicines called statins.  Statins include the medications Crestor, Zocor, Lipitor, Mevacor, Pravachol and others.  The group has a solid base of evidence showing that they prevent strokes and heart attacks in patients with high cholesterol and in patients who have had a stroke or heart attack.

This week, a study published in the New England Journal of Medicine brought us more good news about statins, and potentially broadened their usefulness.  The study has received a lot of attention in the mainstream press.  The study randomized over 17,000 patients who:

• were men over 50 or women over 60
• did not have a history of heart disease, stroke or diabetes
• had normal cholesterol (LDL < 130)
• and had an elevated C-reactive protein ( > 2)

C-reactive protein (CRP) is a blood test that is a general marker for inflammation.  CRP has long been known to be elevated in people at higher risk for heart attack, but until now, there’s never been anything known to decrease that risk.

The patients were randomized to Crestor 20 mg daily or placebo and were followed for an average of almost two years.  The patients on Crestor had fewer heart attacks, fewer strokes and fewer deaths from any cause – a pretty remarkable finding in a group of patients who are not at high risk of cardiovascular illness.

These results strongly support checking a CRP in older men and women and considering statin therapy in those with an elevated CRP regardless of their cholesterol levels.  There are some caveats, though.  This group of patients had a fairly low risk of adverse events and it took a very large number of patients to show a difference between Crestor and placebo.  Extrapolating from the results of the study, it would take treating about 277 patients for two years with Crestor to prevent one heart attack, and 346 patients to prevent one stroke.  Using the current price of Crestor, the cost of Crestor needed to prevent one adverse event is over $170,000.  The price would be less with a generic statin, but it’s still a big expense and a lot of patients taking a statin who don’t benefit.  But we don’t know ahead of time who is the one patient who will have the stroke or heart attack.

So will I recommend checking a CRP to my older patients?  Yes.  Will I recommend statins to patients with an elevated CRP?  Probably, but with the explanation that the benefit may be quite small.

Economists call this the law of diminishing returns.  The more resources you spend on a problem (in this case, stroke and heart attack prevention) the less benefit you get from each incremental increase in spending.  At some point the possible benefit is so vanishingly small that costs aren’t worth it, but that point is different for every patient.  Each one of us has different preferences, different attitudes about risk, and different ways to spend our finite resources.  In a free market each patient would balance the risks and benefits herself, but in our current system in which we all indirectly pay for each other’s medicines the decisions will likely be made by insurance companies and by national expert groups.

(I’m grateful to my colleague Dr. Roy Artal and to the several patients who emailed me about this story.)

Learn more:

New England Journal of Medicine article: Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein

New York Times article: Cholesterol-Fighting Drugs Show Wider Benefit

USA Today article: Crestor would save lives at $500,000 each

My post last week created much confusion and worry.  I received many emails asking “What about me?  Should I keep taking aspirin or not?”

Let me clarify the issue by explaining what we already knew before last week’s study in the British Medical Journal.  We knew that aspirin is valuable in:

• patients who have had a stroke
• patients who have had a heart attack
• patients who have had bypass surgery or angioplasty
• patients with angina (chest pain or discomfort caused by narrowing of coronary arteries)
• patients with claudication (calf pain caused by narrowing of leg arteries)

So patients in the above groups should take aspirin unless they have had an adverse reaction from aspirin.  Last week’s study was not about those patients.

Last week’s study was about patients with multiple risk factors for heart attack but who had not had a heart attack or a stroke.  Risk factors for heart attack and stroke are:

• age (men over 45, women over 55)
• smoking
• high blood pressure
• high cholesterol
• diabetes
• a parent or sibling with a heart attack early in life (male relative before age 55, female relative before age 65)

The US Preventive Services Task Force (USPSTF) and the American Heart Association (AHA) currently recommend aspirin to prevent a first heart attack or stroke for patients with multiple risk factors for heart attack and stroke.  Last week’s study disagreed with those recommendations, suggesting that aspirin does not prevent a first heart attack in high-risk patients.

My friend and colleague, Dr. Yaron Elad, emailed me arguing that I should not change my practice based on a single study.  He and I dug through the studies supporting the USPSTF and AHA recommendations and decided that he was right.  There is still a lot of evidence that aspirin helps prevent a first heart attack in patients at high risk of heart attacks.  So I retract my conclusions last week, and I’m grateful for Dr. Elad’s input.

Finally, and most importantly, talk to your doctor before making a decision.

Learn more:

My post from last week: Aspirin Doesn’t Prevent Heart Attacks in Patients with Diabetes

The US Preventive Services Task Force recommendation: Aspirin for the Primary Prevention of Cardiovascular Events

American Heart Association recommendation: Aspirin in Heart Attack and Stroke Prevention

Aspirin has been a mainstay in the treatment and prevention of cardiovascular disease for decades.

We know that in patients who have had a heart attack in the past aspirin prevents a second heart attack, and during a heart attack aspirin is life-saving.  We also know that in patients with a prior stroke aspirin prevents further strokes.  And in patients with symptomatic narrowing of the arteries, that is chest pressure with exertion (angina) or calf pain with walking (claudication), aspirin prevents strokes and heart attacks.

So on that solid base of evidence, doctors have extended aspirin therapy to many other patients who don’t fit the above criteria but have risk factors for heart attack and stroke, risk factors such as diabetes, smoking, high blood pressure and high cholesterol.  Practice guidelines have been formed recommending aspirin for such patients, despite the lack of evidence that it helps them.  I’ve urged many patients with diabetes, high blood pressure and high cholesterol to start taking daily aspirin.

Well, there’s nothing like a good study to show us that we’ve been doing the wrong thing.  The British Medical Journal published a study this week in which 1276 patients with diabetes and mild, asymptomatic narrowing of the arteries were randomized to receive daily aspirin or placebo.  They were followed for over 6 years to assess differences in the rates of heart attack, stroke, amputations and death.  The surprising result was that the aspirin group did no better than the placebo group.  Aspirin didn’t help.

(By the way, the study also randomized patients to receive antioxidants or placebo, and the antioxidants didn’t help either.)

So to summarize, aspirin should be taken by patients who have had a previous stroke or heart attack, or have symptoms of artery narrowing, such as angina, claudication, or a prior angioplasty or bypass surgery.  Patients taking aspirin because of risk factors for heart disease who have no symptoms of artery narrowing (even though I urged some of you to start aspirin!) should stop.

(Thanks to my colleague and pal, Dr. Rubencio Quintana, for showing me the British Medical Journal article.)

Learn more:

British Medical Journal article: The prevention of progression of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease

UPDATE:  In a subsequent post I retracted my conclusions, offered some balance to the controversy and urged readers to talk to their doctors before changing their aspirin regimen.

In February I wrote about the results of the ACCORD trial, a study designed to test whether strict glucose control in patients with diabetes helps prevent strokes and heart attacks and prolongs life.  The startling results were that the patients with diabetes who were randomized to have their glucose lowered to normal levels died sooner than those with more lax sugar control.

This week the New England Journal of Medicine published the results of another study, the ADVANCE trial, which was designed to answer the same question.  Over eleven thousand patients with type 2 diabetes were randomized to two groups.  One group was managed intensively with a goal of normal blood glucose.  The second group had less strict sugar control.  The groups were followed to measure the frequency of strokes, heart attacks, worsening of kidney disease, diabetic eye disease and death.

Again, in this trial, strict sugar control did not save any lives (though at least, it didn’t cause extra deaths like in ACCORD).  Strict sugar control also didn’t prevent strokes, heart attacks or eye disease.  The one benefit that was detected was that patients with strict control had less kidney disease than patients with lax sugar control.

The common theme seems to be that normal sugars are not the goal of diabetic treatment, or at least not the only goal.  Heart attack and stroke prevention in patients with diabetes involves many other proven therapies like smoking cessation, cholesterol lowering with statins, blood pressure medications and aspirin.

Learn More:

My post in February about the ACCORD trial:  What We Don’t Know About Diabetes

The New England Journal article publishing the results from the ADVANCE trial:  Intensive Blood Glucose Control and Vascular Outcomes in Patients with Type 2 Diabetes

The New England Journal article publishing the results from the ACCORD trial:  Effects of Intensive Glucose Lowering in Type 2 Diabetes

Tangential Miscellany:

I hope us dads all get to spend some time with our kids this weekend, and all of us who are fortunate enough to still have our fathers in our lives have a chance to express our love and gratitude for everything they’ve done for us.  Happy Father’s Day!

This week we learned something very important about diabetes.  We learned that we don’t know something we thought we knew.  (Regular readers will note that this keeps happening in medicine.  For a generation everyone assumes something.  Then we check and discover it isn’t so.)

We’ve always assumed that in type 2 diabetes, the closer to normal that blood sugar is lowered the fewer complications of diabetes patients would have.  Why?  Because diabetes is known to be a major cause of kidney disease, blindness, strokes and heart attacks, and we always assumed these complications are caused by the abnormally high blood sugars in diabetes.

We also have good studies in type 1 diabetes which prove that keeping sugar levels close to normal prevents complications.  So we assumed that this also applied to type 2 diabetes, even though type 1 and type 2 are completely different diseases.

With me so far?  We had lots of good reasons to assume that better sugar control in type 2 diabetes leads to fewer complications, and this assumption has guided diabetes management.  Finally a trial was undertaken to test this belief.  The Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial enrolled over 10,000 people with type 2 diabetes who either already had cardiovascular disease or were at high risk for it.  The patients were randomized to one group which received conventional treatment which lowered sugars but not to normal levels, and another group which received intensive treatment which reduced blood sugars to non-diabetic levels.

This week the ACCORD trial was stopped early because of excess deaths in one group.  What stunned experts and will confuse diabetes management for some time is that the group with excess deaths was the group receiving intensive treatment.  This received a lot of media attention, including this NY Times article and this LA Times article.

So intensive lowering of sugars in type 2 diabetes is worse than more lax control of sugars, at least in patients with multiple risk factors for cardiovascular disease.  The burning questions now are:  What should our goal for blood sugars be?  How low is too low?  Do medicines that lower blood sugar in type 2 diabetes do any good?  No one knows.

For now the experts are calming the public by urging them not to change any of their medicines before discussing it with their doctor, but this reassurance simply covers up the ignorance in which we find ourselves mired.  The scary truth is that as of this week, and until more studies help us, we’re not really sure how we should be treating diabetes.

(I am grateful to Judy F. and Victoria W. for pointing me to the articles.)