The impact of 20%

There’s been a lot of discussion in the DOC about BG test strips.  There’s the strip safely campaign focused on making sure all test strips for sale in the US are subjected to the same rigorous quality control measures to ensure optimal accuracy; many discussions over whether or not 20% error allowed by the FDA is good enough, and countless user experiences.

So, from where does this problem stem? And how big of a problem is it really?  The FDA has imposed an ISO standard on glucose monitoring. The standard is this:

ISO 15197 specifies that

> or =95% of the BG results shall fall within +/-15 mg/dL of the reference method at BG concentrations <75 mg/dL and within +/-20% at BG concentrations > or =75 mg/dL

This means that for BGs less than 75 mg/dL, our meters spit out results that are up to 15% off from reality 95% of the time, and when our BGs are over 75, they can be up to 20% off from reality.  Compliance to this standard is often shown via a Clarke error grid, like the one below (for freestyle test strips).

Clarke error grid for Freestyle Lite test strips. From http://www.diabeticnerd.com

As you’ll notice in the picture, the black dots are all within the region labeled A which is the 15-20% bracket.  You’ll also notice that while the 20% range seems huge for larger BG values, this window is actually quite small for lower BG values.  Also, for any given plasma glucose value, there is a normal distribution of BG values from 0% (completely accurate) to ±20% (with up to 5% of numbers being more than 20% inaccurate). I think it helps to visualize wha this really means by looking at this generic normal distribution:

Normal Distribution: For our purposes, imagine the horizontal axis labeled with -20% on the left where it says “-2σ” and +20% in place of “2σ” on the right. The height of the peak (centered at 0%, “µ”) is determined by the number of BG values that are of by a given percentage.  Notice that 68.2% of your BG values will be in that dark blue region with errors far less than 20%.

Imagine that you kept a running list of the error of every one of your BG meter readings compared to your real plasma blood glucose.  Then you graphed this data with the %error on the horizontal axis and the number of reading per % error on the vertical axis, you’d see a distribution very much like the one in the picture.  Replace the “2σ” and “-2σ” with +20% and -20% and the “µ” with 0% on the horizontal. (I haven’t yet found reliable data to label the y axis with, but it would likely vary from brand to brand and I think it might be reported on that little piece of paper we always throw away when we open a new box of strips.) The light blue tail regions represent the 5% of numbers that are outside of the 15-20% BG allowance and the other 95% are in the two darker blue regions with most being concentrated nearer to the middle which represents your actual BG level.

With that in mind, let’s now consider what effect the FDA regulation has in practice. What I’m really interested in is how this error translates to errors in my diabetes regimen and the impact on my BG/A1C.   Below, I’ll walk you through my calculation of insulin doses delivered based on meter reading and the resulting corrected BGs.  To simplify, I calculated using a 20% error for all BG values from 40-400 mg/dL with a target range of 70-120 mg/dL.

Fisrt, let’s look at the range of meter readings you might expect compared to your real BG.  Keep in mind that these lines contain 95% of all readings, with at least 68% of those readings concentrated closer to the dotted line than either solid line.

Meter Readings 20% accuracy

For every real BG value, your meter is calibrated to correctly identify that value with up to a 20% error. On the horizontal X axis are the real values and the green and red lines indicate the possible range of values returned by your meter.

Using my insulin sensitivity factor, I then calculated the dose of insulin my pump would deliver in response to the meter readings shown above.  Again, remember that numbers are concentrated more closely to the dotted line than either solid line.

Insulin Dose

The error in the meter readings translate to an error in correction dosing. The dashed line shows how much insulin is needed to correct a given BG value to the nearest target (omitting insulin to reach the bottom of the range or dossing to drop to the top of the range). The red and blue lines correspond to correcting a meter value that is 20% above or 20% below the actual value.

Assuming no other influences (ie spherical diabetes in a vacuum), the next graph shows how my BG will respond to getting either the min or max insulin correction.  These represent REAL BG values resulting from inaccurately dosed corrections caused by the 20% error in meter readings. The space between the lines contains 95% of all possible outcomes.

Corrected BG

The range of correction doses lead to a range of corrected BG values. The largest discrepancies occurring alongside the largest real BG values.

And lastly, I converted the above graph into percentages (because I like them).  You’ll see the maximum percent over the target range (red, from under correcting a high or over correcting a low) and under the target range (orange, from over correcting a high or under correcting a low).  This isn’t the % of resulting BG values outside of the range, just the % off from the target of a single BG resulting from inaccuracy in meter readings.  And again, the space between the lines contains 95% of all possible outcomes.

The % above or below the target range of the corrected BG.

The % above or below the target range of the corrected BG.

I’m going to say it one more time because I think it is very important.  These pictures represent the extremes – 95% of BG values are 20% accurate or better, with 68% of the values concentrated closer to reality.  This then means that all of my calculations represent ranges of data with a similar distribution.

So, there it is.  In pictures. The direct impact of the 20% FDA-approved error on our BG values (in a vacuum).

And now for my opinion on the subject: Personally, I feel like it’s just not that big of a deal.  Since I am more likely to treat a low with a standard regimen of 15-30g of carbs and protein, the under correction there is mostly irrelevant.The possibility of over or under correcting a high over 240 is very real but since I’m already in the habit of double checking higher numbers (making sure there’s no rogue sugar on my finger tips) I don’t see that as a huge problem either.  Plus the introduction of a second BG reading is enough to assure me that I’m comfortably in the 68% of readings that are far less than 20% off and not on the outskirts.

Here’s a copy of the excel sheet I used to generate these pictures.  Have fun  if you like that sort of thing and please let me know if you disagree with any of my calculations (or my opinion).

Here are a few other articles and opinions on the 20% issue:

About meters being outside of the FDA limits

Opinion and lots of facts about the FDA and meter accuracy

What the FDA regulations mean to diabetics – blog

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The Glucose Geyser

During a low yesterday,  I made a discovery.  You see, at Company X, we have refrigerators full of free carbonated water.  I typically am not a fan, but we have the stuff laced with fruit essences so I can tolerate it from time to time.  Anyway, so I was low and was munching on a dry and chalky glucose tab, and I felt the need, as I often do, to chase the tab with a swig of water.  Not thinking, I grabbed for a newly opened bottle of lime flavored carbonated water, lifted it to my lips and poured back a sip.  To my surprise, my mouth was instantly full of trillions of tiny carbon dioxide bubbles threatening to explode all over my keyboard.  I manage to keep from spilling and, like any good scientist, decide to check for reproducibility.  Another glucose tab, another swig, another near explosion.  Those of you who regularly consume carbonated beverages may not be surprised by this, but I, who rarely drinks anything but cold water or hot Earl Grey tea, was quite pleased with this new discovery.

So, what are we going to do with this new information? I suggest, a Glucose Geyser (!).  In lieu of adequate outdoor space where messes can be easily cleaned, I have not yet tested my theory, but I expect the situation to play out like this:

Supplies:

2L bottle of carbonated water or other carbonated beverage(anything unsweetened is best for ease of clean up)

6 glucose tabs (preferably of a diameter that will fit easily though the beverage lid)

index card

glucose tab tube, uncapped

Instructions:

  1. Fill the glucose tab tube with glucose tabs, set the index card on top and invert.
  2. Open the 2L bottle and position the glucose tab tube/index card above the opening such that the index card is the only thing separating the tabs from the liquid.
  3. Have spectators stand back (or not if they don’t mind getting a bit wet) then quickly remove the index card so the glucose tabs quickly drop through the opening into the bottle and quickly step back.
  4. Watch as the glucose tab provides a site of nucleation for the carbon dioxide that is dissolved in the liquid causing the liquid to erupt from the bottle with gusto.

At least this is what I hope happens.  If it doesn’t, just replace the glucose tabs with mentos candies.  Or watch this video.

Speaking of Geysers, I am adding in a shameless boast about the vacation M and I just got back from:  Yellowstone is AMAZING! Geysers around every corner! Seriously great vacation. Good on BG lvels too, especially when you utilize some of the less traveled back country trails.  Yay for vacation!

If you try my little experiment, please let me know how it turns out!

Taking Diabetes to Work

I started my new job at Company X last week. I have my very own cubical equipped with my very own computer, phone, and stapler; my very own fume hood equipped with a fancy new Schlenk line, vacuum pump, and shiny stir plates and lab jacks (I am a R&D chemist, btw); a slew of friendly and helpful coworkers; and a comfortable paycheck and benefits package (can you say “Yay! for dental insurance!”). Needless to say I am happy.

However, with a new job comes the need to introduce my diabetes to a new environment and new people. Something that I’m never sure exactly how to approach. Do I let people find out organically and not tell anyone unless it “comes up” or do I “disclose” my diabetes to my boss and few select coworkers as I get to know people? And how will my diabetes react to my new schedule?

The latter has turned out to be the easy part. Relatively speaking. During my first 3 days of work I was low constantly so I reduced just about every rate and ratio by about 10%. Sine then D has been behaving and I think that over time I will have to stepwise adjust my rates back to pseudo pre-job numbers as I develop a routine and begin to settle in.

The tricky part is figuring out how to introduce D to new people. In the past I have tended toward the organic option, making more effort to keep my diabetes under wraps than developing an at-work D-support system. But, I also have never been as conscientious about my diabetes as I am now. But I still don’t feel completely comfortable beginning the disclosure conversation.

My immediate supervisor, JK, already knows – it came out as we were heading off to lunch on Day 1 and he was telling me about his recent vegan conversion (since D is also a bit a bout food choices, it fit right in). His response was typical. “Oh, that’s interesting. My [insert distant relative here] died just last week from diabetes. She didn’t even know she had it before she was rushed to the hospital with a blood sugar of 900.” Yeah, mine isn’t like that. I explained to him that I have type one, had it since I was six. I wear an insulin pump and am otherwise completely healthy. That his distant relative is the exception, not the rule.

Then he stepped into the role of supervisor and asked me if there was anything he needed to know. I told him that I keep my diabetes well monitored but I could let him know the signs of low blood sugars and the appropriate emergency response, but really all I need is that he’s aware so that in case of an unrelated emergency he can make inform anyone else who needs to know. There. D-introduction done. Right?

The next day, the was training me on some piece of equipment when my BG began to trend low and Dex felt the need to inform me. Loudly. So I pulle doff my glove, reached into my pocket to silence Dex and put on a new glove. When I looked up, JK looked concerned and asked if everything is ok. I blushed and simply said “yep – everything’s fine” and the training continued.

Now I think that maybe I need to sit him down and give a breif tutorial about my different bionic parts, the noises they make, and the implications of those noises. The last thing I want is to be sitting in a meeting, have Dex go off, and have everyone think that I’m reaching in my pocket to return a text or something. I’d rather the explanation be preemptive.

But I don’t know how to begin that conversation. Despite my new found comfort with D, I’m still uncomfortable talking about it with people unfamiliar with D.

Then there’s the conversation I had with another coworker who was interested in seeing pictures of my hedgehog, which I have on my phone. She pointed to my pocket and said, “Do you have your phone with you?” As if she thought that even though I said I left my phone at my desk, I had something clearly cell-phone like in my pocket so I must’ve been mistaken. I told her that I did not in fact have my phone with me but would definitely show her later. I could have said a million other things. I could have told her what was in my pocket, showed her even. I could have brought her into the loop but I choked. And D remains under wraps.

I’m thinking of being really bold and beginning to wear my pump and Dex outside of my pockets at work. The idea behind this is two-fold. First, it would make life in the lab a bit easier. I would have better access to these devices and would be less likely to accidentally contaminate something by having to reach into my pocket to see them. Second, although people still wouldn’t necessarily know what they are, it would be more obvious what they aren’t and maybe these conversations would come more organically.

I’d be very interested in hearing how other people have approached introducing D at work. Please comment if you have any stories or insight.

The science behind the glucose test strip

There’s a lot of talk in the DOC about making a more accurate BG test strip. We want a test strip that is inexpensive with as little error as possible. That’s not too much to ask. Or is it? I decided to look into how current BG strip technology works and do a few basic calculations to see just how big of a difference there is between blood with a BG of 40 verses that with a BG of 300 mg/dL.

Test strips contain two chemicals; an enzyme called “glucose oxidase” which is transforms glucose into gluconolactone, and a “mediator” (typically ferricyanide) which participates in the reaction and produces ferrocene and releases electrons.  The electrons make up the current that the meter then interprets as a BG value.  When there is a higher concentration of glucose in the blood there will be a higher concentration of electrons produced which will cause an increase in the current sent across the electrode on the strip, and a higher BG reading is obtained.

Other compounds which are often found in the blood also transform the ferricyanide into ferrocene and release electrons.  (Such as acetomenophen, vitamin C, and uric acid.)  To prevent this from skewing the test results, each test strip has two working electrodes (plus a reference).  One working electrode has both of the chemicals I described above, and the other has only the mediator but no enzyme.  Thus both electrodes measure the current that results from acetomenophen, vitamine C, and uric acid, but only the electrode with the enzyme also measures the current produced by the glucose reaction.  This allows the meter to subtract out the current that results from these other compounds in the blood.

Current meters can measure as little as 36,000 molecules of glucose in 30uL of whole blood (uL = microliter, most strips use about 3uL).  A single gram of glucose contains around 3,400,000,000,000,000,000,000 molecules (that’s 3.4×10^21).  After thinking about all of this, I began to wonder just how different 40 mg/dL blood is from 300 mg/dL blood.

I decided the best way to compare would be to figure out what mass percent these numbers translate to.  I found online that the approximate density of blood is 1.05 g/mL which is equal to 1.05 mg/uL (which means that 1uL of blood has a mass of approximately 1.05mg).

A BG reading of 95mg/dL can easily be converted to mg/uL by dividing by 100,000.  So,  95mg/dL = 0.00095 mg/uL (I chose this BG value since it is within range of a nondiabetic person’s average BG thus the density of blood given online should be most correct at this level.) This means that in 1 uL of blood, there are 0.00095mg of glucose  (or 3.23×10^15 molecules).

To get a mass% (the percent of the total mass of the whole blood that is glucose) just divide the mass of glucose in 1uL by the mass of 1uL of blood: 0.00095/1.05 = .000904 or 0.0904%.

Using the same math, a BG of 40 mg/dL = 0.038% and has 1.36×10^15 molecules per uL, and a BG of 300 mg/dL = 0.285% with 1.02×10^16 molecules in 1uL.  These differences are actually quite miniscule if you think about it.

[It is important to note that outside of the range of a non-diabetic blood sugar level, the density is going to change.  At elevated BGs, the actual density might be higher, making the number calculated using the above rational somewhat elevated, and the low BG levels will appear somewhat lower than the actual value. However, with these tiny percentages, the change in density is very likely minimal and can thus be disregarded.]

In my experience as a chemist, I have found that analytical equipment varies in price depending on the level of accuracy.  For example, for every additional decimal place that a balance is capable of measuring, the price of that balance increases exponentially.  We are essentially asking these companies to produce a product that measures the concentration of the glucose in our blood to an additional decimal place.  I would be willing to bet that the technology already exists, but the cost is well outside of what any of us can afford to pay.

Before our meters become more accurate, one of two things needs to happen.  The materials needed for a more accurate test strip using current technology need to get cheaper, or someone needs to figure out an entirely new way of measuring glucose (or at least some new chemical coatings for the electrodes).

So, that’s the way it is.  Now, feel free to form whatever opinion you’d like 😉