Day to Day Variations in Blood Glucose

[We Hope]

This is probably more than you wanted to know about meters and altitude, but yes, it can affect them just as temperature extremes (hot or cold) can:

http://www.liebertonline.com/doi/abs...ournalCode=dia

Effect of High Altitude on Blood Glucose Meter Performance

"Diabetes Technology & Therapeutics. December 2002, 4(5): 627-635
Participation in high-altitude wilderness activities may expose persons to extreme environmental conditions, and for those with diabetes mellitus, euglycemia is important to ensure safe travel. We conducted a field assessment of the precision and accuracy of seven commonly used blood glucose meters while mountaineering on Mount Rainier, located in Washington State (elevation 14,410 ft). At various elevations each climber-subject used the randomly assigned device to measure the glucose level of capillary blood and three different concentrations of standardized control solutions, and a venous sample was also collected for later glucose analysis. Ordinary least squares regression was used to assess the effect of elevation and of other environmental potential covariates on the precision and accuracy of blood glucose meters. Elevation affects glucometer precision (p = 0.08), but becomes less significant (p = 0.21) when adjusted for temperature and relative humidity. The overall effect of elevation was to underestimate glucose levels by approximately 1-2% (unadjusted) for each 1,000 ft gain in elevation. Blood glucose meter accuracy was affected by elevation (p = 0.03), temperature (p < 0.01), and relative humidity (p = 0.04) after adjustment for the other variables. The interaction between elevation and relative humidity had a meaningful but not statistically significant effect on accuracy (p = 0.07). Thus, elevation, temperature, and relative humidity affect blood glucose meter performance, and elevated glucose levels are more greatly underestimated at higher elevations. Further research will help to identify which blood glucose meters are best suited for specific environments."

http://care.diabetesjournals.org/content/28/5/1261.full

Performance of Glucose Dehydrogenase–and Glucose Oxidase–Based Blood Glucose Meters at High Altitude and Low Temperature

"Blood glucose meters using the enzyme glucose oxidase (GO) have been proven unreliable at high altitude. A new test strip technology, based on the oxygen-insensitive enzyme glucose dehydrogenase (GD), has been utilized by some manufacturers.

"Five plasma-calibrated blood glucose meters were evaluated in this study, four glucose dehydrogenase based (GD1: Precision Xtra; GD2: Ascensia Contour; GD3: Accu-Chek Compact; and GD4: Freestyle) and one glucose oxidase based (GO1: OneTouch Ultra), with capillary blood samples from one of the investigators.

"First, all meters were tested in a hypobaric chamber at simulated altitudes (at 20°C in chronological order with ∼8-min intervals) of 0, 4,500, 2,500, and again 0 m above sea level, with normal (∼5.8-mmol/l) and high (∼16.5-mmol/l) plasma glucose values (n = 6 at all conditions). At 4,500 and 2,500 m altitude, the glucose oxidase-based meter (GO1) overestimated plasma glucose values by 15 ± 0.1% (mean ± SD) at the normal blood glucose level and 6.5 ± 0.5% at the high blood glucose level, as compared with the readings at 0 m.

"Comparatively, three glucose dehydrogenase–based meters overestimated readings of normal and high blood glucose levels (GD1 by 6.5 ± 0.2 and 1.5 ± 0.7%, GD3 by 3.7 ± 0.1 and 3.5 ± 0.4%, and GD4 by 0.8 ± 0.2 and 0.8 ± 0.4%, respectively). The fourth, GD2, underestimated readings of normal and high blood glucose levels by 1.9 ± 0.2 and 4.2 ± 0.9%, respectively.

"In addition, three glucose dehydrogenase–based meters (GD1, GD2, and GD3) were tested with blood at up to 5,895 m above sea level during the ascent of Mount Kilimanjaro, Tanzania. In the presence of both high altitude and low temperature, the meters diverged from each other. At the summit, 5,895 m above sea level, the readings of the investigator’s plasma glucose concentration were 2.8, 11.9, and 21.0 mmol/l (GD1, GD2, and GD3, respectively).

"In this study, all four glucose dehydrogenase–based meters performed better than the glucose oxidase–based meter at high altitude, as hypothesized.

"In conclusion, people with diabetes who intend to participate in activities at high altitude or, in particular, at low temperature, should be informed that blood glucose meters may give totally unreliable false low or high readings."

This deals with a change in the chemicals in the test strips which make it possible for the meter to read the blood drop. I believe most to all meters are now using the newer system, glucose dehydrogenase method.

http://www.diabetesselfmanagement.co..._the_altitude/

"I lived in Leadville, Colorado (10,000 feet) and worked at the hospital there. We would frequently have companies come in to do tests on new glucose monitoring strips because they had to prove that the strips worked at altitiude. If we would let them poke our fingers several times we would receive a stipend in cash.

"When I moved to that elevation from about 4000 feet, I had to increase my basal insulin a couple of units."

Posted by MR | Mar 14, 2007 at 1:52 pm

http://web.archive.org/web/200702031...-July-2005.pdf

This Diabetes Health Meter Review is 4 years old, but it gives you an idea of the altitude limit on some of the meters on page 2.

The new vet sounds like the right one!

Kathy

Adding here-altitude information on ReliOn Micro from the online owners' guide:

http://www.relion.com/content/diabet...cro_Manual.pdf

Page 71

Altitude (up to) 10,000 feet

[We Hope]

Day to Day Variations in Blood Glucose

From the DVM side of diabetes:

http://avmajournals.avma.org/doi/abs...rnalCode=javma

Journal of the American Veterinary Medical Association
February 1, 2003

Evaluation of day-to-day variability of serial blood glucose concentration curves in diabetic dogs

Linda M. Fleeman, BVSc Jacquie S. Rand, BVSc, DVSc, DACVIM
Department of Companion Animal Sciences, School of Veterinary Science, The University of Queensland, St Lucia, QLD 4072, Australia. (Fleeman, Rand)
Objective—To evaluate day-to-day variability of serial blood glucose concentration curves in dogs with diabetes mellitus.

Animals—10 dogs with diabetes mellitus.

Procedure—Paired 12-hour serial blood glucose concentration curves performed during 2 consecutive days were obtained on 3 occasions from each dog. Dogs received the same dose of insulin and meal every 12 hours on both days. For each pair of curves, comparison was made between the results of days 1 and 2.

Results—Mean absolute difference (without regard to sign) between days 1 and 2 for each parameter was significantly > 0, disproving the hypothesis that there is minimal day-to-day variability of serial blood glucose concentration curves when insulin dose and meals are kept constant. Coefficient of variation of the absolute difference between days 1 and 2 for each parameter ranged from 68 to 103%. Evaluation of the paired curves led to an opposite recommendation for adjustment of the insulin dose on day 2, compared with day 1, on 27% of occasions. Disparity between dosage recommendations was more pronounced when glucose concentration nadir was < 180 mg/dL (10 mmol/L) on 1 or both days. In this subset of 20 paired curves, an opposite recommendation for dosage adjustment was made on 40% of occasions.

Conclusions and Clinical Relevance—There is large day-to-day variation in parameters of serial blood glucose concentration curves in diabetic dogs. Day-to-day variability of serial blood glucose concentration curves has important clinical implications, particularly in dogs with good glycemic control. (J Am Vet Med Assoc 2003;222:317–321)

http://www.vin.com/proceedings/Proce...4008&O=Generic

WSAVA 2008

Feline Diabetes--An Update
Thomas Schermerhorn, VMD, DACVIM(SAIM)
Department of Clinical Sciences, Kansas State University
Manhattan, KS, USA

Variability in Blood Glucose Curves

"Despite the widespread recommendation for the use of blood glucose curves to monitor the effectiveness of diabetic management, the technique is unreliable, inaccurate and suffers from poor repeatability. In one study, the large degree of variability between serially obtained glucose curves observed in dogs would have led to conflicting recommendations for insulin therapy in >50% of patients (Fleeman and Rand, 2003). Significant variability is also observed in diabetic cats when curves obtained at-home are compared with those obtained in-hospital (Casella, et al, 2005) or when consecutive at-home curves are compared (Alt, et al, 2007a). The variability detected in the canine and feline studies likely has numerous sources, not all of which can be adequately controlled. Sources of variability that might influence glucose curve results include analytic variability (human error introduced when obtaining or analyzing the sample), technologic variability (variability/error caused the instrumentation used to make the measurements), and individual variability (caused by inherent biologic fluctuations)."

http://www.vin.com/proceedings/Proce...4010&O=Generic

ACVIM 2008

Diabetic Phenomena--All Those Interesting Metabolic Happenings
Michael Schaer, DVM, DACVIM, DACVECC
University of Florida, College of Veterinary Medicine
Gainesville, FL, USA

Variables Affecting SQ Insulin

Dose: the larger the dose, the longer the absorption time and duration of action.

Injection site: mobile body parts (limbs) can allow for faster absorption.

Depth of injection: IM route allows for faster absorption compared to SQ route. Remember, only regular crystalline insulin [R] can be given IM.

Environmental temperature: insulin will be absorbed faster in warmer environment because of increased peripheral blood supply.

Insulin Absorption Variability

"This will be affected by insulin type, injection site, subcutaneous protease activity, and exercise. There are rare human diabetics who have increased subcutaneous tissue protease activity and therefore cannot benefit from SQ insulin injections. Alternative treatment routes are necessary in such patients. I have been suspicious for this when one canine patient required approximately 200 units of NPH insulin twice daily."

http://www.vin.com/proceedings/Proce...4009&O=Generic

WSAVA 2008

Troubleshooting Persistent Hyperglycemia in Treated Diabetics
Thomas Schermerhorn, VMD, DACVIM(SAIM)
Department of Clinical Sciences, Kansas State University
Manhattan, KS, USA

"In humans, glycemic control can be upset by stress or emotional strain as well as seemingly innocuous departures from the patient's ordinary routine, such as unusual exposure to sunlight or increased physical activity. Presumably, similar factors could affect diabetic control in dogs and cats, so careful questioning of the pet's owner is warranted. Hunting or service dogs, for example, might experience increased insulin needs when working. Similarly, it is conceivable that a cat with a preference for a particular window sill might absorb insulin more rapidly on especially sunny days. In addition to routine questions about appetite, water consumption, urinary and defecation habits, and general attitude, the owner should be questioned about the diet, administration of non-prescribed medications or supplements, changes in the home environment or any unusual events. Owners often do not realize the importance of these factors and will not offer the information unless specifically asked.

"Changes in the home environment or daily routine might also disrupt glucose control. Some events are clearly stressors on the patient, such as new pets or people in the household, a recent move to a new home, recent illness or surgery, but others are less obvious. One diabetic cat treated by the author developed PH after a newly installed glass door allowed it to encounter neighborhood cats on the other side of the glass. While it is important to consider any change in the patient's environment as potentially contributing to PH, it is equally important to resist placing too much emphasis on relatively minor changes unless all other causes of PH have been thoroughly investigated and ruled out.

"The glucose curve is the simplest way to document whether a dog or cat truly has PH throughout the day. The traditional serial glucose curve is useful for monitoring blood glucose concentrations over time but recent studies have highlighted the low reproducibility of this technique, even when performed under ideal conditions. As the technique can yield vastly different results even when performed only 12-hrs apart under the exact same conditions, care must be taken not to place too much weight on a single glucose curve result.

"Delayed insulin absorption may lead to PH. Insulin absorption from a subcutaneous site in humans can vary as much as 50% from day-to-day, even if the same insulin, dose, and injection site are used. As alluded to earlier, insulin absorption and action in humans can also be affected by variations in countless factors associated with daily life, including physical exercise, body temperature, and the emotional state. While there are few studies in dogs and cats examining variables that alter insulin absorption and action, it is likely that there is a high degree of true day-to-day biologic variability in these species as in humans. Biologic variability is distinct from the variability introduced by human error and the technology used for insulin administration and glucose measurement. Other potential causes of delayed insulin absorption include interference by insulin antibodies, which develop in response to exogenous insulin, and poor blood flow at the site of injection, which can occur when the injection is administered in adipose tissue."

http://www.intervet.com.au/binaries/82_103335.pdf

Page 8

"There is day-to-day variability between glucose curves despite patients receiving the same insulin dose and meal. The reasons for inter-day variability may be attributed to variations in the amount of insulin administered, insulin absorption, availability of insulin in the plasma to the insulin receptors, the level of peripheral insulin sensitivity, variations in food intake, and physical activity. Unfortunately, the main causes of variability are patient related and cannoe be controlled. Because of daily variability, the results of blood glucose measurements should always be interpreted conservatively."

[We Hope]

Re: Day to Day Variations in Blood Glucose

From the MD side of diabetes:

http://web.archive.org/web/200611010.../bern178.shtml

The Laws of Small Numbers – Part 2
Richard K. Bernstein, M.D., F.A.C.E., F.A.C.N., C.W.S

"When you inject insulin, not all of it reaches your bloodstream. Research has shown that there’s a level of uncertainty as to just how much absorption of insulin actually takes place. The more insulin you use, the greater the level of uncertainty.

"When you inject insulin, you’re putting beneath your skin a substance that isn’t, according to your immune system’s way of seeing things, supposed to be there. So a portion of it will be destroyed as a foreign substance before it can reach the bloodstream. The amount that the body can destroy depends on several factors. First is how big a dose you inject. The bigger the dose, the more inflammation and irritation you cause, and the more of a “red flag” you send up to your immune system. Other factors include the depth, speed, and location of your injection.

"Your injections will naturally vary from one time to the next. Even the most fastidious person will unconsciously alter minor things in the injection process from day to day. So the amount of insulin that gets into your bloodstream is always going to have some variability. The bigger the dose, the bigger the variation.

"A number of years ago, researchers at the University of Minnesota demonstrated that if you inject about 20 units of insulin into your arm, you’ll get on average a 39 percent variation in the amount that makes it into the bloodstream from one day to the next."

http://www.aafp.org/afp/991115ap/2343.html

Type 1 Diabetes Mellitus & Use of Flexible Insulin Regimens-Hirsch-American Family Physician-1999

"Several important factors affect the absorption of subcutaneously administered insulin and explain much of the unstable glycemia that occurs in patients with type 1 diabetes. The time it takes to absorb one half of an injected dose of insulin may vary by 25 to 50 percent among individual patients.5 For example, NPH insulin may have a duration of activity of 18 hours in one patient but an effective activity of only 9 or 10 hours in another patient.

"Factors affecting the bioavailability and absorption rate of subcutaneously injected insulin are listed in Table 1. Because so many factors affect insulin absorption, exact pharmacokinetic profiles cannot be provided."

http://www.ncbi.nlm.nih.gov/pubmed/1...?dopt=Abstract

Variability of insulin absorption and insulin action.
Diabetes Technol Ther. 2002;4(5):673-82.

"Subcutaneous (s.c.) injections of identical insulin doses may lead to considerable intra- and inter-individual differences in the current metabolic control of patients with diabetes mellitus. This well-known variability of the metabolic effect of insulin hampers practical insulin therapy considerably.

"There are no appropriate studies available investigating the variability of the metabolic effect after s.c. insulin administration in patients with diabetes.

"In summary, the intra-individual variability of the metabolic effect observed after insulin application, be it subcutaneously injected or be it inhaled, is considerable and, therefore, hampers practical diabetes therapy. To date no means have been found that could lead to a clinically relevant reduction in the variable metabolic effect."

http://care.diabetesjournals.org/con...pl_1/s106.full

American Diabetes Association

"Whenever possible, insulin-using patients should practice self-monitoring of blood glucose (SMBG). Insulin dosage adjustments should be based on blood glucose measurements. SMBG is extremely valuable in patients who take insulin because they experience day-to-day variability in blood glucose levels. This variability is influenced by differences in insulin absorption rates, insulin sensitivity, exercise, stress, rates of food absorption, and hormonal changes (e.g., puberty, the menstrual cycle, menopause, and pregnancy)."

[k9diabetes]

Re: Day to Day Variations in Blood Glucose

This is likely some of the work that led vets to give up on curves and go to fructosamine tests.

However, I would contend that the curve, even with variability, gives you FAR more information than a fructosamine test. To me, this study underscores the importance of looking at trends in curves over individual readings. I have gotten a lot of good information from laying one curve over the top of another and seeing the patterns that are common to them as far as when the insulin is working and when the food is being digested.

These studies also suggests to me that we probably tend to think of blood glucose levels as more stable day to day than they actually are.

We so often go looking for something to change when we see unusual numbers and I think "unusual numbers" are actually fairly common - that they are "normal" and probably do not require any adjustments other than to make sure that regulation is loose enough to accommodate some off days.

It's not that I don't like really good regulation. I absolutely do. But not at the cost of creating instability due to lows, rebounds, and corrections and, maybe more importantly, not at the cost of nonstop worry about their blood sugar. Chris had good regulation most of the time but he wandered and he definitely had off days. A dog can be imperfectly regulated and have a great quality and quantity of life.

We tried to balance our desire for good regulation with the knowledge that he'd be fine even if he didn't get there and that neither one of us should have to be focused every single moment on his blood sugar or his regulation. That living life is more important than flawless regulation.

I have seen so much worry here about "the numbers" and trying to get every reading down into the hundreds every day. For a lot of dogs, and people for that matter, it just isn't a realistic expectation. And it doesn't need to be an expectation. I am an advocate of aiming for the best you can get in terms of regulation and the best includes a regimen that allows everyone, canine and human, to have a life beyond diabetes!

Okay, off soapbox...

Natalie

[We Hope]

Re: Day to Day Variations in Blood Glucose

"There are rare human diabetics who have increased subcutaneous tissue protease activity and therefore cannot benefit from SQ insulin injections. Alternative treatment routes are necessary in such patients. I have been suspicious for this when one canine patient required approximately 200 units of NPH insulin twice daily."

Rare cases like this appear to affect the insulin receptor.

http://ucsdnews.ucsd.edu/newsrel/hea...pertension.asp

Finding a Single Mechanism
for Hypertension, Insulin
Resistance, and Immune Suppression

"The bioengineering researchers at UC San Diego’s Jacobs School of Engineering also showed that a drug developed for unrelated purposes in humans was effective in counteracting the underlying molecular mechanism in the spontaneously hypertensive rat (SHR), a strain predisposed to develop high blood pressure.

"In the circulation of SHR rodents, Schmid-Schönbein and DeLano found significant levels of proteases, which are enzymes that break down proteins. Natural enzyme inhibitors found in normal healthy rats did not lower the level of protease activity in the SHR strain to normal levels.

"“We were looking for a common cause of diverse but concurrent metabolic problems and we were testing our theory that enhanced proteolytic activity in the circulation may be the root cause,” said Schmid-Schönbein. “In the hypertensive rat we studied, enzymes cleave extracellular portions of several protein receptors, such as the insulin receptor, so that insulin can no longer bind and facilitate normal metabolism of glucose.”

"Under normal conditions, the pancreas releases insulin in the bloodstream. The molecule then binds to insulin receptors on the cell-surface membrane, which signals the cells to absorb glucose, a main source of cellular energy. However, when a cell loses the binding site for insulin on the insulin receptors, it becomes “resistant,” or unresponsive to insulin and no longer absorbs glucose in healthy amounts on cue, which is the problem in type 2 diabetes."

In the case of the rats, they had working pancreases, but the idea of the need for the insulin to bind for it to work is the same when you need to treat with insulin.

My "old timers" (those who have been dealing with diabetes since childhood) have always told me the last place they start making adjustments is to their basal. Some of them refer to it as "background" insulin, meaning it works quietly in the background taking care of the body's needs minus food.

http://www.rch.org.au/diabetesmanual...fm?doc_id=2744

Royal Childrens' Hospital, Westmead, Australia

Guidelines for insulin adjustment

Long—term adjustment

"Look for a pattern in readings over a few days or longer (eg- high readings before breakfast). Three days of readings above the target range or two days of readings below the target range at the same time of day should make you think about the need for adjustment.

"Identify the insulin that is acting to regulate readings at this time of day (eg- the pre—breakfast reading is mostly regulated by the previous evening’s long—acting insulin). Adjust the appropriate insulin (see below for a guide on how much to adjust). In general- adjust only one insulin at a time. Adjusting more than one at a time can be confusing.
Wait a few days to assess the outcome of the adjustment before making further changes.

Exceptions to these general guidelines are:

"Hypoglycaemia (especially if severe) or periods of increased activity or sick days may require more rapid or frequent adjustment.
"Where your doctor or educator advises more frequent changes"

So you can see that people don't start making radical changes to their routines unless the readings they're getting look to be part of a trend.