More Diabetes Answers

Why would you ever want to use Avandia... or even Actos?

Just over a decade a go a new class of drugs burst onto the diabetes treatment scene with much hyperbole and excitement.  The thiazolidinediones (or TZDs) were said to target one of the root causes of type 2 diabetes - improving the body's resistance to insulin.  But almost from the onset the problems and serious side effects associated with TZDs began to become clear.

The first of the TZDs (launched in 1996) was troglitazone (Rezulin).  It caused severe irreversible liver failure in some patients and it couldn't be predicted who would get that problem.  Several hundred people have died of liver failure as a results of treatment with Rezulin and so it was taken off the market in 2000.  The response by many doctors and patients was simply to switch to a newer TZD.

The next of the TZDs was rosiglitazone (Avandia).  While it does not appear to cause liver problems there is a long list of other serious side effects that it causes.  It causes people to retain too much fluid in their body and to develop heart failure at a much faster rate than people who do not take Avandia.  It causes weight gain and it causes people to develop thinning of the bones (osteoporosis) which increases the risk of fractures (which can be very serious indeed in older people who have diabetes).  All of these were minimized by the drug companies and by people promoting the use of Avandia because they claimed that patients who kept taking it would ultimately get more benefit because of reduced complications of diabetes and fewer heart attacks and strokes.  But more and more studies have shown that this is just not true.  In fact people who take Avandia are MORE likely to develop heart failure, or get a heart attack or a stroke than patients who don't take this drug.  On balance it is becoming clear that Avandia causes more harm than good.  Fewer people are now being put on this drug but even in 2009 sales for Avandia were over a billion dollars.  And many thousands of patients who are being taken off Avandia are simply being switched to the third and last remaining member of this class of drugs.

The last of the TZDs is pioglitazone (Actos) and I am sure that the company who makes it are delighting in the bad press that Avandia is getting.  A recent study in the Journal of the American Medical Association (JAMA) published online yesterday compared rosiglitazone (Avandia) and pioglitazone (Actos) in over 220,000 Medicare patients from 2006-2009.  This study showed clearly that, compared with pioglitazone, rosiglitazone was associated with an increased risk of stroke, heart failure and death.

National Public Radio had a nice story about this study on June 28th:

http://www.npr.org/templates/story/story.php?storyId=128174678

But how good is pioglitazone?  In truth we don't yet know for sure.  It certainly causes unwanted weight gain.  It certainly causes a significantly increased risk of developing heart failure and of getting osteoporosis leading to bone fractures.  Whether it increases or decreases your chance of being alive in 5 or 10 years remains to be proven.

Fifteen years ago before the thiazolidinediones appeared on the market people with type 2 diabetes could improve their chances of staying alive and well by doing things to REDUCE their risk of heart attacks and strokes (like quitting smoking, eating healthy, getting regular exercise, and taking statins, ACE-inhibitors, low dose aspirin, and keeping their blood pressure in a good range), and taking drugs like metfomrin sometimes supplemented with insulin to keep the blood glucose levels close to normal.  And if you have diabetes you still CAN do all of those things.  I see no evidence that the millions of people in the USA and around the world have had their lives improved by the use of the TZDs.  And if I had diabetes myself I would certainly NOT take any of them... not even Actos.

The power of groups: why one plus one is wa-a-a-ay more than two!

I spent the morning with one of my favorite colleagues, Dr. Jeff Gelgisser.  Jeff is a family practice doctor in Redmond, Washington who looks after a lot of people who have diabetes. 

A few years ago Jeff went through his list of diabetic patients and found a dozen or more who didn't come in very often and who had blood glucose levels and blood pressure levels that were too high and who weren't getting their eyes and feet screened as often as they should. 

 

When he called them up he found:

• Some of these people just preferred to ignore their diabetes. 
• Others just didn't like the way they were treated when they came in to the clinic. 
• Some felt lonely and isolated as if no-one understood how hard it was for them to deal with diabetes along with everything else in their lives. 

They had stopped coming in because they knew that the doctor or nurse who saw them would lecture them about how "bad" they were at looking after themselves.

Jeff then did a rather brave thing.  He invited them to come in as a group and vent their frustrations to him and his staff.  He encouraged them to share ideas with each other and he took the time to explain things to them that they were frustrated about and didn't understand. 

 

And something magic started happening.  Many people in the group changed from feeling hopeless and angry to feeling motivated to change things about how they were living their lives.  They shared positive ideas with each other.  They set new goals for themselves. 

 

They wanted to keep meeting.  They celebrated each other's successes and supported and comforted each other when new difficulties arose. Most all of those people now have lower blood glucose and blood pressure levels, are eating healthier, exercising more, are taking their medicines better and feel much better about their overall lives.

 

Jeff and his team have held group meetings like this for several years now.  Once a year they ask me to join them to answer questions about new research findings in diabetes or anything else that is on their minds.  I am honored to attend.  I always leave feeling more positive and optimistic about my life, too.

There are lots of different types of "group visits" for people with diabetes and other chronic illnesses.  One very successful and popular program was started by Dr. Kate Lorig and colleagues at Stanford. 

It is called "Living Well with Chronic Conditions"

 

You can search for that phrase on the Internet to see if there is a group near where you live. Another great resource for learning how to set up and organize group visits is at www.improvingchroniccare.org.

How NOT using a cool new treatment improved our approach to wound care

Several years ago a drug company approached me to try to convince me to start using a new kind of "growth factor paste" to help speed up how fast wounds or ulcers on the feet and legs of diabetic patients would heal.  They gave me the results of of a randomized controlled trial in which half the patients were given the real "growth factor paste" and the other half were given paste with no active ingredients in it.  The growth factor paste was expensive and had some unpleasant side effects in some patients but on average wounds treated with the paste healed several days faster.  The result was statistically significant (so was unlikely to be caused by random chance) but the improvement was only healing a few days faster over a several week period so I wasn't sure if it was worth the extra cost and risk of the side effects.  Before deciding whether or not to recommend adding the new growth factor paste I got together with my colleagues.  We picked out forty or fifty patients with lower leg ulcers in our clinics to see how fast we were healing them ourselves.

The results were striking.  Even the placebo group in the research trial (the ones who weren't getting the growth factor paste) healed much faster than most of our cases!  How could that be? Well, in the research trial all the patients were seen by expertly trained nurses who followed the same protocols when they treated patients with foot ulcers.  They did a comprehensive assessment every time.  They recorded exactly how long and broad and deep the wound was every time they saw the patient.  They cut away the dead skin around the ulcers.  They cleaned them and dressed the wounds the same way every time and they saw the patients back frequently until the ulcer was healing well.  They taught the patients how to change their wound dressings and how to look for signs that things were not going well.  Now when I looked at our own wound cases some of those good things happened some of the time but they didn't all happen every time.  Sometimes a patient would be seen but the size of the ulcer was not recorded.  Sometimes they were left to go too long before they were seen again.  They might be seen by a different person the next time who, not knowing how big the wound had been the last time, didn't know if it was improving or getting worse. different doctors and nurses in different clinics used different approaches to how they treated wounds.  No one was talking to each other or sharing their results and nothing was being tracked, so no-one could learn or improve.

So after discussing this with my colleagues we came to two conclusions.  First, there was no point in adding expensive new growth factor paste onto a chaotic system where no two wounds were being treated the same way.  Second, we needed to change the way we were treating our wounds.  We needed to look at the published medical literature and visit wound care "Centers of Excellence" to learn the best way to treat wounds.  We then needed to develop rules and expectations that used these good approaches and teach that to all of the doctors and nurses who treat patients with wounds.  Everyone would follow these rules.  Everyone would record their results and progress in the same way.  We would share results with each other.  We would learn together and keep improving.

So what happened?  Once we put this new "evidence-based wound care system" in place and trained our doctors and nurses to do it the right way every time we started healing wounds much faster than we ever had before.  We review results at every clinic every week.  We coach people to improve.  We share results with each other and change the "evidence-based protocols" whenever we find a new and better way to do something.  When that change is made everyone makes that change and this becomes the new "standard approach" for managing wounds.  The doctors and nurses are much happier with their work, now, take pride in how well they are doing, and more importantly, patients are getting their wounds healed faster and fewer of them are losing their legs.

Standard work: the boring way to innovate?

I spent yesterday morning with a very lively and passionate group of nurses who help heal ulcers and wounds.  They work all over the Puget Sound region in medical clinics and urgent care facilities helping people with diabetes and other conditions that lead them to have ulcers and wounds on their feet and legs.  When a foot ulcer is not well managed it can be disastrous.  Infection can spread through the skin and muscles into the bones of the feet, into the bloodstream and that can lead to a deadly blood borne infection called septicemia.  If a foot ulcer is not well managed the person may have to have their foot or leg amputated.  It is one of the most feared of all the complications of diabetes.  It is easy to see why these nurses are so passionate about what they do.  When their treatment works well they are saving feet, legs, and lives.

They were meeting to share ideas with each other but more important than that, to agree that they would all start treating wounds and foot ulcers the same way.  Many of them did not like that idea.  Over the years they had learned some tricks that they were sure worked for them.  Some of them were reluctant to change and do things the way someone else was doing it.  So why did they agree to change?  Because when we all looked at how well their patients were doing it wasn't nearly as good as they thought, or as good as it could be.  They used different dressings for the wounds.  Sometimes they got doctors to put the patients on antibiotics, sometimes they didn't.  They didn't all evaluate the wounds in the same way.  They didn't always write down how long, wide and deep the wound was.  So if that nurse was off for a few days and the patient came in to see someone else that person didn't know whether the wound was smaller or larger than when they were seen before.  So the new person couldn't tell if the wound was getting better or worse.  The nurses varied in how often they saw patients with wounds, and on how much of the surrounding dead skin they should cut off to allow the wound to heal better.

It turns out that many of the technical details of treating wounds have been studied in well-designed research trials.  So we know how often to see someone back, when to use antibiotics and when they are not needed.  We know the best way to cut off the dead skin, how to record treatment properly and when patients need to be referred on for more advanced treatments (like putting the patient in a hyperbaric oxygen chamber or having surgery to increase the circulation to the feet).  But over the years some of the nurses had forgotten those research results or had been told to do things a different way by doctors.  They had got sloppy with the way they wrote down their treatments.  They liked to try new and different things just to see if it would help.

But although it may seem boring to all agree to treat wounds in a standard way it is the most powerful way to improve things.  If everyone agrees to assess wounds in the same way, agrees to record the length, width and depth of the wound at every visit, and agree to how to cut of the dead skin and on how to check for infection and to see if their is enough blood going to the wound then it is much easier to compare how everyone is doing.  Once everyone is treating wounds in a standard way then it becomes much easier to improve the treatment.  If one of the nurses thinks of an improvement to the standard treatment (perhaps because she read about a new research study that proved that a new dressing speeded up the healing) then all of the nurses in all the different clinics can try the new dressing.  If they all agree that this speeds up the healing then the new dressing can become part of the NEW standard work for healing wounds.

Luckily, by the end of the day yesterday these talented and passionate nurses agreed that they could learn best from each other if they agreed to do things in the same boring standard way, then compare their results, and try to look for better ways to improve their care.  So the standard work doesn't stay standard and boring for long - it keeps improving over time so that more and more patients get their ulcers to heal faster and avoid losing their legs.

Is lower always better? (Part 1 - blood glucose control)

Even though I have been studying diabetes and helping people with diabetes to live better with it for over thirty years, I still get surprised constantly when a new study challenges my firmly held assumptions!  One message that has been pushed down our throats for over twenty years at least is that the lower your blood glucose levels are the better.  Yes, we are told, it can be a nuisance pushing your blood glucose levels closer and closer to normal because you run the risk of feeling weird or even passing out from a too low blood glucose (hypoglycemia) and you may need to check your blood glucose more often and may gain weight but over the long haul you will stay healthier if your average blood glucose levels are kept as close to normal as you can.  It is a simple message to push.  Organizations like the American Diabetes Association have pushed the message hard.  All the big pharmaceutical companies who make drugs that help push your blood glucose lower and lower have a vested interest in pushing the message that "lower is always better, and even lower is better still!"  But some recent research studies have challenged this simple message.

The ACCORD trial is a large randomized controlled research trial carried out in many different medical centers around the world.  In the study 6,779 people with type 2 diabetes were randomly assigned to a "standard" approach to lowering their blood glucose where they aimed to get their HbA1c between 7-8% and keep it there or to an "intensive" approach where they tried to get their HbA1c as low as they could get it and keep it there (You can read the full study results in the journal Diabetes Care 33:721-727, 2010).  These subjects had had their diabetes for several years and many of them had had heart disease already (angina, or a heart attack) or had risk factors for heart disease (like high blood pressure or a history of smoking or heart disease in their family).  After about five years of follow up the standard therapy group achieved an average HbA1c of 7.5% whereas those in the intensive treatment group kept their HbA1c at 6.4%.

The surprising results of the study were that after 4-5 years of follow up there were more deaths in the intensive therapy group than in the standard therapy group.  This was even more noticeable in people who had had very poor HbA1c levels to begin with and in people who had worse nerve damage (neuropathy) at the start of the study.

Another study published in the Lancet this year (Currie, CJ, et al.  Lancet 375:481-489, 2010) looked at over 50,000 people with type 2 diabetes treated in general practice in the United Kingdom.  The researchers followed what happened to those people after they had their diabetes treatment intensified by having an extra blood glucose lowering pill or insulin added to their treatment.  As you would expect their HbA1c levels dropped lower after the new treatments were added.  But when they looked to see how those people did in the next few years they found that those whose HbA1c levels stayed high were more likely to die and that those with a lower HbA1c did better... but only up to a point.  It was bad to have a HbA1c of over 9.0% for example.  Those who got it down to 8.5% did better and those at 8.0% or 7.5% did better still.  However, if the new treatment pushed the HbA1c down below 7.0% the outcomes started to get worse with more people dying if their HbA1c was at 6.5% and even worse if it was 6.0%.

So what does this mean for you?  There is no doubt that high blood glucose levels (HbA1c over 9.0%) are bad for your long term health and working to bring it down is a good thing to do.  However, how low to push it is more complicated.  I think it depends on what type of diabetes you have, how long you have had it, what your average blood glucose levels (HbA1c) have been for the past few years and whether or not you have risk factors for heart disease.  For people with type 1 diabetes or people with type 2 diabetes who have always had HbA1c levels that are below 8.0% and who don't have risk factors for heart disease then pushing to keep your HbA1c level down below 7.0% is probably a good thing to prevent long term problems from your diabetes.  But if you have had heart disease (or have several risk factors for heart disease like smoking or having high blood pressure and high cholesterol) and if your HbA1c has often been above 8.0% in the past few years then these research studies suggest that a better target for you might be to keep your HbA1c around 7.5%