More Diabetes Answers

Why is NOT being an "early adopter" uncomfortable but might be a good thing?

You have probably seen lots of adverts on TV for new drugs to help improve your sex life, lower your cholesterol, allow you to eat salty, spicy, food without heartburn, and generally make your life better.  The adverts often show everyone looking happy and have actors dressed as earnest, sincere doctors in white coats advising you in reassuring tones that you should, "Ask you doctor about fill-in-the-blank." Then at the very end of the advert in an incomprehensibly fast rush a different voice blurts out all the fine print (including side effects, or the fact that a new fat-lowering drug actually hasn't been shown to prevent heart attacks and strokes and might in fact increase your risk of stomach bleeding... check out the website at www.lovaza.com ) 

What's a person to do when the main message is that more is better and than anything new is most likely a huge scientific advance forward and therefore a good thing.

But often it takes years before we really know if a new therapy will actually improve real health outcomes that matter to people.  There have been many examples of drugs that seemed like they were doing good but ended up causing more harm than good.  Back in the 1970s and 1980s there was a big push to give people drugs to stop the heart developing irregular rythmns after a heart attack.  Seemed like a no-brainer.  If you've just had a heart attack you wouldn't want your heart to suddenly go into irregular rythmns.  And these drugs (like encainide and flecainide) did work to make the electrical tracings of the heart (the ECGs or EKGs) look better.  But unfortunately when researchers looked at the outcomes in patients who received the new "miracle" drugs more of them died than patients who did not receive the drug.  Sometimes a drug that helped lower blood pressure (like short-acting nifedipine) can actually increase the risk of heart attacks or stroke.  Sometimes pain killers (like Vioxx) that appear to be better because they cause less risk of stomach bleeding can actually cause an increase in heart attacks.

As I have talked about in other blog postings the story with the thiazolidinediones is another example of a class of drugs that looked promising but may be causing more harm than good.  We won't know for sure for another few years.

I work for a health care organization (Group Health in Washington State) that holds itself to a very high standard.  Before we add any drug to our formulary so that our patients can get it we try to wait until there are long-term studies that show clearly that the drug is beneficial.  When those studies are published we move very fast to contact all of our patients who might benefit and offer them the drug.  But it also means that when a new drug is being hyped up by the drug companies but before we truly know if it will be beneficial we do NOT add it to our formulary.  For patients (and some of our doctors) who buy-in to the hype I often have to deal with some unhappy and angry phonecalls.  It often feels uncomfortable to be cautious and conservative.  We take a lot of heat for not being out front with "cutting edge" drugs. 

But despite the discomfort of fielding angry phone calls in the early years of new drugs, I take comfort in this.  We never had Vioxx on our formulary at Group Health.  We never had Rezulin or Avandia or Actos on our formulary either.  I don't know how many hundreds of patients are alive today because of our cautious approach because they did not get heart attacks or die as a result of taking these drugs but it does probably run into the hundreds at least.

Again, let me be clear:  I have nothing against the company who makes Lovaza and I don't know whether it will turn out to cause more good than harm.  I hope it will.  But none of will know that until larger long-term trials are done.  We do know that it causes significant side effects.  Once we know for sure that the benefits outweigh the risk we will jump on it and prescribe it widely.  But not until then.

What will history say about the thiazolidinedione class of diabetes drugs like Avandia and Actos?

Every time I hear another piece of bad news about rosiglitazone (Avandia) or pioglitazone (Actos) I feel as though I am watching another piece of diseased flesh falling off a bloated and dying giant.  The thiazolidinediones (or TZDs or glitazones) was the juggernaut new "blockbuster" diabetes drug class of the past ten years.  Despite having no research studies showing long term benefit these drugs were pushed very persuasively onto the market.  But as I have detailed in previous posts the longer we looked the longer the list of problems and side effects grew while the evidence of meaningful benefit remained elusive.

http://gomeworld.typepad.com/morediabetesanswers/2010/06/why-would-you-ever-want-to-use-avandia-or-even-actos.html

This weeks brings more bad news.  The FDA has issued a warning that pioglitazone (Actos) may cause an increased risk of bladder cancer, especially with prolonged use of the drug.  We already know that the risk of developing bone-thinning (osteoporosis) with these drugs gets worse the longer you stay on them.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm226257.htm

Another announcement today states that rosiglitazone (Avandia) is being taken off the market in Europe because of the likely increased risk of heart attacks, strokes and deaths associated with taking Avandia.  Avandia will, of course, still be available in the USA market.  Although sales in the USA are dropping Avandia still brings in annual revenue of over a billion dollars.

http://link.email.washingtonpost.com/r/BZYGW4/A7M5IB/30Y38H/VMINCB/Q0A68/E4/h

Why is it that the USA seems so much slower to act as Europe just did?  This is eerily reminiscent of the situation back in 1997 when troglitazone (Rezulin), the first drug in this class, was taken off the market in the UK with most of Europe quickly following suit, but was left on the US market for another full two years before the rising toll of deaths from liver failure convinced the FDA to remove it.  I wonder how long we will need to wait before we see the last of Avandia in the USA.

I do not write this with pleasure or malice.  I have nothing against pharmaceutical companies that work to develop new treatments that might benefit people with diabetes.  Far from it.  I applaud their efforts.  In the past few decades some other classes of drugs (like ACE-inhibitors and statins) have been proven over time to be dramatically beneficial for people with diabetes.  What concerns me is how easily fooled many doctors and patients are, and how readily we all want to believe the early hype about new drugs.  How impatient we all are.  We are rarely willing to do the rigorous long-term trials that can truly prevent us from allowing millions of people to be exposed for years to drugs that cause more harm than good.

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%

Should I worry about my triglycerides, too?

Most everyone worries about their cholesterol these days.  Even when you are relaxing watching a sports game on TV it seems like every other advertisement seems to mention heart disease and cholesterol levels and tells you which pills you should ask your doctor about to lower your cholesterol level.  There is good reason for this.  Cholesterol is a kind of fat that floats around in your blood and can become deposited in the lining of your arteries to increase your risk of getting heart attacks, and strokes, and other bad things.  So in addition to eating a healthy diet and getting exercise it is important for many people with diabetes to take a drug that can lower the LDL cholesterol (often called the "bad cholesterol").  The most common, powerful and effective types of drug to lower LDL cholesterol and protect you from getting heart attacks and strokes are the statindrugs (like simvastatin [Zocor], atorvastatin [Lipitor] and others).  Most people with diabetes who are over age 40 should consider taking a statin drug.

But there is another type of fat that floats around in our blood called triglycerides and that can sometimes cause problems, too.  The normal range for triglycerides in your blood is less than 150 mg/dl (1.7 mmol/L).  If the triglyceride level gets very high (above 500 mg/dl, or 5.6 mmol/L) it can cause a very dangerous inflammation of your pancreas (called pancreatitis) and so most doctors know that they should treat very high levels of triglycerides.  But what if your triglyceride is just a bit higher than normal but not really high?  Suppose your triglyceride level is between 150-350 mg/dl.  Should you take drugs to bring that down into the normal range?  Another part of the famous ACCORD trial looked at this question and came up with a very interesting results.

I have written about the ACCORD trial in several other posts in this blog. In this part of the ACCORD trial 5,518 people with type 2 diabetes (at an average age of 62), many of whom already had heart disease or two or more risk factors for heart disease were studied.  These patients were already taking simvastatin, one of the powerful statin drugs to help lower their LDL cholesterol and protect them from having heart attacks and other bad cardiovascular events in the future.  Many of these people also had triglyceride levels that were in the 150-350 mg/dl range.  The ACCORD researchers wanted to know if outcomes would be even better if they added another type of drug called fenofibrate.  Fenofibrate is a drug that can lower triglyceride levels.  So half the subjects got fenofibrate added to their drug treatment while the other half got "dummy pills" (or placebos) that looked like the fenofibrate pills but didn't contain any active drug.

After almost five years of follow up the levels of triglyceride in the blood were quite a bit lower in the group who were taking fenofibrate than in the group taking the placebo pills.  However, the number of bad cardiovascular events (like heart attacks and strokes, some of which were fatal) was notany lower in the subjects who took fenofibrate compared to those who took the dummy pills.  In fact among women in the study the overall rate of bad events was higher(9.1%) in those taking the fenofibrate compared to those taking the placebos (6.6%)!

What lesson can we learn from this study?  First of all it teaches us that focusing on an improvement in a lab test is much less important that focusing on outcomes that really matter to us (like preventing heart attacks,strokes and deaths).  It also teaches us that sometimes the side effects of a drug cause more harm than the condition it is trying to treat.  So if you have diabetes and are already taking a statin drug to get your LDL cholesterol under 100 mg/dl and if your triglycerides are only slightly above the upper end of the normal range then taking a drug like fenofibrate is not likely to protect you from heart attacks in the future and may even increase that risk, if you are a woman.

Can I mix my fast-acting and long-acting insulins together?

The answer, of course, is, yes you can, but I will try to convince you not to!  Obviously it is more convenient to mix your fast-acting insulin (like Regular, or lispro [Humalog], or aspart [Novolog], or glulisine [Apidra]) in the same syringe as your long-acting insulin (like NPH, or glargine [Lantus], or detemir [Levemir]) and give it as one shot instead of two separate shots.  In fact some insulin preparations already come mixed together.  There is an insulin called 70/30 that is 70 percent NPH insulin mixed up with 30 percent Regular insulin.  We are supposed to believe that the 30% of fast-acting Regular insulin will be absorbed first, giving us a peak of insulin in the first 2-3 hours after taking the shot and that the 70% of longer-acting NPH insulin will kick in later giving us a second peak about 6-10 hours after we take the shot.  The problem is that this is NOT what happens at all.  After all, what is NPH insulin?  It is Regular human insulin with "junk" added to the bottle to slow it down.  the "junk" is a fish protein called protamine and a suspension of zinc molecules.  When you draw up more Regular insulin into the same syringe as the NPH then this Regular insulin also gets "slowed down" by the cloudy mixture of protamine and zinc. Instead of getting an early peak from the Regular and a second slower peak from the NPH you get one single peak that happens half way in between when the Regular peak and the NPH peak would be expected.  Now this works fine for some people but if you really want to get a quick peak to cover the carbohydrate you are eating in a meal and then get a slower, flatter second peak from the NPH insulin it works much better to give each insulin as a separate shot.

A recent study looked at this with two of the popular insulin analogs.  Eleven people with type 1 diabetes who were taking the fast-acting insulin lispro (Humalog) and the long-acting insulin glargine (Lantus) were asked to take them as separate shots on one day and the same doses mixed together in the same syringe on a second day (This study was published recently in the journal, Diabetes Care, 33:1009-1012, 2010 by Cengiz, E, Tamborlane, WV, and colleagues).  What they found was that the rapid peak from the lispro was lost entirely when it was mixed with the glargine insulin.  This meant that the blood glucose rose higher in the first few hours after a meal (because there was no early peak from the lispro to help bring the blood glucose down as the food from the meal was absorbed).  A few hours later the blood glucose dropped lower causing hypoglycemia because the insulin levels were now too high after all the food had been absorbed.

So when you mix fast-acting and long-acting insulins together you lose the beneficial effects of rapid peaks of insulin to cover your meals and the flat, steady, basal insulin level between meals.  Even if it means having to poke yourself a few more times you get more flexibility and control of your blood glucose levels if you give your fast and long-acting insulins as separate shots.

Is lower always better? (Part 2 - blood pressure control)

In The Diabetes Answer BookI talk a lot about heart disease.  The biggest risk to your future life and health if you have diabetes is from heart disease.  If you have diabetes it is incredibly important that you do everything you can to lower your risk of heart disease.  If you smoke do everything you can to quit.  If you are over age 40 talk to your doctor about whether you should be taking a statin drug, or an ACE-inhibitor drug, or low dose aspirin.  Ask to get your cholesterol checked and try to keep the LDL cholesterol level below 100mg/dl (2.6 mmol/L).  And keep track of your blood pressure.  High blood pressure increases your risk of getting a heart attack.  Doing things to lower your blood pressure will keep you healthy and alive longer.  Nothing that I have said so far is surprising, new, or controversial.  The controversial part is to ask the question, "How low should we push the blood pressure level?"

When someone measures your blood pressure they give you two numbers.  The first number is higher.  This is called the systolic blood pressure and tells you how much pressure your heart generates when it is pumping. There is no doubt that having your systolic blood pressure at 150 is better for your long term health than having it at 170, for example.  Having your systolic blood pressure below 140 is better still, and we have been told for years that if you have diabetes you should try to get it below 130.  But would an even lower number be better still.  If you took enough medicines, drugs, and pills to push your systolic blood pressure below 120 would you live a longer and healthier life?

This very question has recently been asked in a large, well-designed, randomized controlled research trial called ACCORD.  In this study 4,733 people with type 2 diabetes, whose average age was 62 and who had had heart disease or at least two risk factors for heart disease were given two different approaches to treating their blood pressure.  Half of them were treated to get their systolic blood pressure below 140.  This group kept their blood pressure at an average of 133 for the next 4-5 years.  The second group were treated to try to get their blood pressure below 120.  they kept it at an average of 119 for the next 4-5 years.  In order to get their blood pressure at this lower level the people in this more intensive treatment group needed to be on more drugs and in bigger doses than the people in the less intensive treatment group.  Because of that the intensive group had more side effects from their treatment.  But the big question was, would they do better when they were followed up?  Would they have fewer heart attacks, and strokes? Would more of them stay alive and well during the 4-5 years of follow up? Surprisingly, the answer to those questions was NO!  Both groups did equally well.  About the same number died or developed a new cardiovascular disease (like a heart attack or a stroke).

So where does this leave us? Does the ACCORD trial tell us what the ideal systolic blood pressure is if you have diabetes?  Well, it does confirm that high blood pressure is not good for you if you have diabetes.  Getting the systolic below 140 is definitely a good goal to go for.  And, in fact, the people in the ACCORD trial who were trying to get their blood pressure below 140 ended up at 133, which is a lot closer to 130 than 140. So maybe a target of less than 130 (which is what the American Diabetes Association and other international group recommend right now) is the right target.  I wish the ACCORD trial had had a third group who were targeted to get their systolic blood pressure below 130, but they didn't.  What the study reminds us is that when taking drugs to treat any medical condition there is a balance between the drugs doing good and causing harm.  Sometimes adding more drugs and pushing the dose higher and higher only results in more cost and more side effects and may not always result in more benefit.