More Diabetes Answers

Can HbA1c be used to diagnose diabetes?

Although glycosylated hemoglobin (or HbA1c) has been used for thirty years, now, to allow us to know how well a person's diabetes is controlled, it has never been used to actually diagnose someone as having diabetes in the first place.

To understand what HbA1c is go to this link:

http://gomeworld.typepad.com/morediabetesanswers/2010/01/what-is-glycosylated-hemoglobin-or-hemoglobin-a1c-hba1c.html

For years the only way to diagnose diabetes, or to screen people to see if they have diabetes, was to measure their blood glucose level after they had had nothing to eat for at least ten hours (called a Fasting Blood Glucose level) or to measure blood glucose at a random time of the day or after a heavy meal or a large glucose drink.

A normal fasting blood glucose level is less than 100mg/dl (5.6 mmol/L).  A fasting blood glucose level over 125mg/dl (6.9 mmol/L) means the person has diabetes, and a value in between 100 and 125mg/dl means that the person has impaired fasting glucose (sometimes called Impaired Glucose Tolerance).  People in this last category are at higher risk for developing diabetes in the future.

A random blood glucose under 140mg/dl (7.8 mmol/L) is normal.  A random blood glucose level over 200mg/dl (11.1 mmol/L) means the person has diabetes, and a value between 140 and 199mg/dl means that the person has impaired glucose tolerance and is at higher risk for developing diabetes in the future.

When using either a fasting blood glucose or a random blood glucose to diagnose diabetes we require that there are TWO abnormal values on different days.  This is to make sure that the first measurement wasn't just a laboratory error or mistake.  This can happen from time to time.  A tube of blood can get labeled for the wrong patient.  The person might have just finished eating a donut and had sugar on their skin when the finger prick blood sample was taken.  Although rare, it is possible to get a wacky result from a lab test.  We would not want to tell someone that they had diabetes unless we were very sure, and so we always like to have two abnormal tests done on different days.

Starting on January 1st 2010 the worldwide medical community (led by the American Diabetes Association, or ADA) has agreed that HbA1c can be used to diagnose diabetes.  This is great news. HbA1c can be measured any time of day so you don't have to be fasting for ten hours before getting the test done.  HbA1c is a very sensitive and reliable test which gives an average of all the ups and downs of blood glucose in the previous twelve weeks.  The other good news is that it is still okay to use the previous tests (based on fasting or random blood glucose measurement).  But now finding a HbA1c that is 6.5 percent or higher on two occasions can also be used to diagnose diabetes.

So if you someone is tested in the middle of the day and has a random blood glucose over 200mg/dl AND a HbA1c of 6.5% or higher then they have diabetes.  Or if they come in fasting and have a fasting blood glucose over 125mg/dl AND a HbA1c of 6.5% or higher then they have diabetes.

The ADA did two other things, one of which is good and the other of which is a bit confusing.  The good thing is that they have stopped using the term "Prediabetes" which I have always thought is a sloppy and inaccurate term (read my answer to "What is Prediabetes?" in The Diabetes Answer Book pages 39-40).  Instead the ADA lists "Categories of increased risk for diabetes," which includes impaired fasting glucose (100-124 mg/dl) or impaired random blood glucose levels of 140-199 mg/dl. But when they define the level of HbA1c that gives an increased risk for diabetes they say 5.7-6.4%.  Now if the normal non-diabetic range for HbA1c is 4.0-6.0% then it does make sense that anyone with a HbA1c level of 6.1%, 6.2%, 6.3%, or 6.4% is above normal but not yet high enough to be called diabetes.  But someone with a HbA1c level of 5.7%, 5.8%, 5.9%, or 6.0% is still in the normal range!  Why should we think of them as being at increased risk for diabetes in the future?  Well, these various cut points to define what it "normal," what is "slightly abnormal" or "impaired" and what is "really abnormal" or "diabetic" are somewhat arbitrary cut points.  Over the past few decades groups of scientific researchers have argued about where to put these cut points and have changed their minds several times!

It certainly makes sense to think that someone who has a HbA1c level in the upper end of the non-diabetic normal range (5.7-6.0%) is probably at a higher risk for developing diabetes in the future than someone who has a HbA1c level in the lower end of that normal range (4.0-4.9%).  For me, the fact that we can now use HbA1c to diagnose people with diabetes and can identify people who do not have diabetes yet but are at increased risk is a good thing.

Can a bleeding ulcer cure diabetes!?

Just the other day one of my patients thought that her diabetes had been "cured" after being in hospital with a bleeding stomach ulcer.  When she came out of the hospital her HbA1c, which had previously been in the 8.0 -9.0 percent range, came back at 4.9 percent!  She was delighted until I explained the reason.  She had lost several pints of blood from her bleeding ulcer and so was quite unwell with severe anemia when she was admitted to hospital.  In order to treat her she had been treated with a transfusion of several pints of blood.  That blood had been donated by one or more non-diabetic individuals.  When this was mixed with her own blood the average amount of HbA1c dropped right into the normal range because the transfused blood had very little glucose attached to it.  Over the next 10 to 12 weeks I'm afraid that my patient's HbA1c will rise back up to the 8-0 percent range as glucose gets attached to her own hemoglobin and to the hemoglobin from the transfused blood.

To understand more about HbA1c look at page 83 in The Diabetes Answer Book or check out this post:

What is glycosylated hemoglobin (or hemoglobin A1c, HbA1c)?

http://gomeworld.typepad.com/morediabetesanswers/2010/01/what-is-glycosylated-hemoglobin-or-hemoglobin-a1c-hba1c.html

Does insulin glargine (Lantus) cause cancer?

What a great, if scary, question!  I'm afraid the answer that I give you is not as straightforward as you would like.  The answer is, "Probably not, but we don't know for sure."  You might wonder why someone even asked such a question.  I mean if you have diabetes then insulin is just the hormone that your body doesn't make enough of.  Taking insulin should be good for you, not bad for you, right?  Absolutely.  Insulin has been a miraculous advance in the treatment of diabetes and the millions of people who take insulin are much healthier because of it.  So why wonder if insulin glargine (Lantus) might cause cancer?  Let me tell you what is and is not known.

By looking at large populations of people around the world researchers have known for well over a decade that people who are very overweight and people who have type 2 diabetes have an increased risk for several types of cancer (cancer of the colon, cancer of the pancreas and cancer of the breast).  It is not known why.  One possible reason is because people who are overweight and people with type 2 diabetes have a lot more insulin in their body and insulin stimulates the growth of cells, so maybe it stimulates the growth of abnormal cancer cells.

Researchers have done experiments in laboratories showing that insulin can stimulate the growth of breast cancer cells.  Insulin glargine (made by the Pharmaceutical Company Sanofi-Aventis) is an analog of human insulin.  This means that the scientists have modified the natural human insulin molecule by removing certain parts of the molecule (amino acids) and adding extra ones.  This is done all the time to create new drugs to treat all kinds of illness.  People who take steroid inhalers for asthma or steroid pills to treat their arthritis are taking analogs of the natural steroid hormone, cortisol, that we all make in our bodies.  So insulin glargine (Lantus) is a modified kind of insulin that is a bit different from naturally occurring human insulin.  Well, it turns out that in laboratory studies insulin glargine stimulates cell growth even more strongly than natural human insulin, so it is certainly possible that people taking Lantus to treat their diabetes could have a higher risk of cancer.

What's the best way to know for sure?  By far the best way would be to find a large number of people (several thousand at least) with type 2 diabetes who need insulin treatment and ask them if they would let you randomly assign them to use insulin glargine (Lantus) or another insulin (such as human NPH insulin, perhaps).  It is likely that they could get similar improvements in their blood glucose levels and could have their diabetes controlled with either insulin for many years.  Then, we would keep track of how they were doing for 5, 10, 15 years or more.  During that time some of those thousands of people would get cancer and some of them would die from cancer or from other causes.  Because the people were randomly assigned to either Lantus or NPH at the beginning, if we found a different rate of cancer or death between the two groups of people that would be very powerful evidence.  We would know with confidence whether one type of insulin gave less risk of cancer than the other.  Unfortunately that study has not been done.

There has been a small study where 1017 patients were randomized in this way and during four years of follow-up there were 20 new cases of cancer in the people taking glargine insulin (Lantus) and 31 cases in patients taking human insulin.  In other words the patients taking Lantus insulin seemed to be LESS likely to develop cancer than those taking human insulin.  The trouble was that there were too few people in the study and they weren't followed for long enough for us to know for sure.

Well, if no one has done a larger and longer study like this (a randomized controlled trial) how else might you answer this question?  You could try looking to see what happened to the many thousands of people who have been started on different types of insulin over the past decade or so.  This is called a cohort study.  For those of you who want to learn more details about the advantages or disadvantages of cohort studies compared to randomized controlled trials (RCTs) the entry in Wikipedia is very helpful:

http://en.wikipedia.org/wiki/Cohort_study

 One of the problems with a cohort study is that you can never be sure why particular patients were started on particular types of insulin.  It certainly wasn't random!  And so you never know whether what you find is because of the type of insulin the person is taking or because of some other factor that you don't know about.

Here's a great example of why you should be very cautious about drawing conclusions from cohort studies.  After the end of World War 2 the number of households that had a radio in them went up dramatically over the next decade.  During that same decade the birthrate also went up dramatically.  If you were naive you could conclude that having a radio in your house increases the risk that you will get pregnant!  But if you had done a randomized controlled study after World War 2 where half the households had been given radios and the other half were not given radios I  seriously doubt that you would have seen a difference in the birth rates in those two groups!

When large groups of people (over 100,000) with type 2 diabetes who were taking insulin in Germany and in the United Kingdom were studied the number of people who developed cancer while taking insulin glargine were slightly lower than those taking other types of insulin.  But when the researchers divided up the patients into those who were taking a small, medium or large dose of insulin, and when they looked at those who took only one type of insulin compared with those who took more than one type of insulin they concluded that patients who took only insulin glargine, and took it in high doses, were at higher risk for developing cancer.  This has set off a flurry of angry name-calling in the medical journals with various experts criticizing each other for the methods they have used and the conclusions that they have come to.  Truthfully the only way to know for sure would be for some important regulatory agency like the Federal Drug Administration (the FDA) to demand that a large randomized controlled trial be done.

So where does this leave you, if you are a someone taking insulin glargine (Lantus)?  I think that with what we know today for sure the benefits of taking it far outweigh the risks.  If some group of researchers do decide to do a proper randomized controlled study to see whether taking insulin glargine (or any other kind of insulin) causes a lower or higher risk of cancer that would be great.  I would love to know the answer.  But for now I suggest that you continue to take the insulin you are taking and focus on things that you CAN do to lower your risk of cancer in the future.  Don't smoke.  Don't drink alcohol to excess.  Eat a healthy diet. Get regular exercise.  Do something fun every day.  Try to keep your stress level down.

Is blood glucose testing a waste of time?

This may seem like an odd question to you but in the almost thirty years since home blood glucose testing has become widely available there has been a lot of debates between academic researchers on this topic.  A recent study came out suggesting that if you had type 2 diabetes you could get your average blood glucose level (as measured by glycosylated hemoglobin, or HbA1c) to the same level whether you tested your blood glucose or not.  I remember a similar study being done over twenty years ago to "prove" that self-blood glucose monitoring was "unnecessary" in type 1 diabetes.  In these studies people with diabetes were randomly divided into two groups.  Both groups were seen frequently by the research nurses and doctors and were encouraged to increase their pills and insulin to the maximum doses that could be tolerated without getting side effects, including low blood glucose levels (hypoglycemia).  The results of these studies has usually been that both groups of subjects end up at the same level of HbA1c which, to the researchers, "proves" that self-blood glucose testing is not necessary.

I do not agree with that interpretation of those studies.  It would be like dividing people into two groups and asking them to get through a dense forest on a pitch black night but only giving one group flashlights.  In truth, both groups would get through the forest eventually.  The group without the flashlights might take longer and would have more bumps and bruises from hitting unexpected trees, but they would all get through if they were persistent enough.  To me that does not prove that flashlights are unnecessary, however.

As you can tell if you read The Diabetes Answer Book I really like comparing blood glucose self monitoring to carrying a flashlight.  The whole purpose of using self-glucose testing is to allow you to know what your blood glucose is at different times of the day and night, before or after meals, and when you are feeling peculiar.  It "shines a light" on the situation to let you understand what is going on.  So whether you have type 1 or type 2 diabetes and whether you use pills or insulin or both to treat your diabetes a blood glucose monitor helps you to see how your blood glucose levels change in response to changes to treatment or to other things going on in your life.  I bet you that if any of those academic researchers got diabetes themselves they would prefer to do self-blood glucose testing rather than just blindly increasing their doses of pills and insulin until they got side effects or got hypoglycemia!

Like most tools that are available to us in life they are only useful if we know how to use them and how to interpret the results that they give us.

What if I disagree!?

   I hope that you find the answers that I give to be helpful and sensible but maybe you disagree with some of the things that I have said.  I am happy to engage in some friendly and respectful conversation with you about any of my answers that you disagree with.  Some topics are more controversial than others.  I will listen to your point of view, and will try to explain why I agree with you or why we may just have to agree to disagree!

New Questions

I have tried to cover a wide variety of common, practical, and puzzling topics in The Diabetes Answer Book but I am quite sure I have left things out that you may want answers to.    If there is a question about diabetes that you don't think I answered I invite you to ask it by posting a comment to this post.  If I think it is a good topic that other people might be puzzled about too then I will post the answer on this blog.  I will also take the best of those questions and include it if we do a second edition of The Diabetes Answer Book.  I have attached a comment to this post to give you an example of how to do it.  You click on comment, enter your name and contact e-mail (which is kept private) and then post your comment or question.  When you are done you are asked to verify that you can read some letters and numbers (this is done to prevent automatic robots from posting comments and questions!)  I will check these comments and questions and will publish and respond to any that I think would be helpful to other readers of this weblog.

Follow-up Questions

If you have read my answer to one of the questions in The Diabetes Answer Book and don't fully understand the answer or if you have a follow-up question please write a comment to this post.  Be sure to say which chapter and which question you are referring to.  I will try to give a more detailed answer in response and will post it here on the blog for you and others to read.  I have attached a comment to this post to give you an example of how to do it.  You click on comment, enter your name and contact e-mail (which is kept private) and then post your comment or question.  When you are done you are asked to verify that you can read some letters and numbers (this is done to prevent automatic robots from posting comments and questions!)  I will check these comments and questions and will publish and respond to any that I think would be helpful to other readers of this weblog.