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For decades, people with diabetes have known the drill: prick your finger, get a good-sized drop of blood, apply the drop of blood to a meter, wait for the result and adjust your insulin, eating or exercise regimen accordingly.
For several, this has always been a painful and cumbersome process. In the late ’90s, however, good news came to the millions who had to go through this routine.
In December 1998 and January 2000, Amira Medical of Scotts Valley, California, and TheraSense of Alameda, California, were respectively granted approval by the U.S. Food and Drug Administration (FDA) to sell their alternate-site testing meters. Designed for testing in areas of the body that have fewer nerve endings than the fingertips (the forearm, thigh and upper arm), requiring less blood than standard fingertip meters and being virtually painless, these meters were a benefit to people with diabetes.
Now, controversial new information has recently come to light concerning alternate-site testing. A German research team has concluded that there are a few instances when testing on the forearm—instead of the fingertip—can result in risky delays of high- and low-blood-sugar detection. In addition, an FDA advisory committee recently held an October 29 meeting that was to "address problems associated with using blood samples from alternate sites, such as the forearm, upper arm, thigh, calf or base of the thumb."
At press time, that meeting had not yet taken place.
A Risk to People with Diabetes?
In a paper published in a recent issue of Diabetes Care (24:1303-1304, 2001), Karsten Jungheim, MD, and Theodor Koschinsky, MD, PhD, of the German Diabetes Research Institute, suggest that alternate-site testing may pose a risk to patients with diabetes who base their treatment decisions on the results.
For their study, capillary blood-sugar samples using an alternate-site meter were taken after an overnight fast from the fingertip and the forearm of six male type 1s, age 26-54 years, who were on intensified-insulin treatment. In place of the usual pre-breakfast insulin, patients drank a high-glucose mixture in order to reach a blood-sugar value between 300 and 400 mg/dl. After this, the subjects were intravenously given their usual short-acting insulin. The decrease in blood-sugar levels was followed every five to 15 minutes by testing both the arm and fingertip until the level steadied or the patient reached a hypoglycemic state.
Researchers Test From the Forearm and Finger Tips—How Inaccurate Is It?
Koschinsky says that in the fasting state, the average blood-sugar value at the fingertip (121 mg/dl) and forearm (124 mg/dl) were similar for all patients. However, when rising, he discovered there was an 87 mg/dl difference between blood-sugar values taken from the finger tips and forearm. The average blood-sugar reading from the forearm at this time was 208 mg/dl, while the blood-sugar reading taken from the finger tips was measured at 295 mg/dl.
Also, in one patient with hypoglycemic unawareness, there was a 106 mg/dl variance between the two samples. Blood-sugar values were measured at 53 mg/dl at the fingertip vs. 159 mg/dl at the forearm.
Additional findings by Koschinsky showed that, compared with the fingertip, it took an additional 27 to 34 minutes until the capillary blood-sugar levels at the forearm reached hypoglycemic values. In other words, it took this long for people testing on their forearms to know they were in a hypoglycemic state.
Koschinsky told Diabetes Health that this 27 to 34-minute delay is a concern for people with diabetes, because they are in danger of overlooking an already existing hypoglycemia. He also says, in the Diabetes Care article, that problem with delayed blood-sugar readings at the forearm has not "been fully recognized as a potential problem by the certifying administrations in the United States or Europe." He adds that "even a few minutes of delay in detecting hypoglycemia could un-necessarily endanger the life of people with diabetes."
In Defense of Alternate-Site Testing
Geoff McGarraugh, director of chemistry for TheraSense of Alameda, California, criticizes Koschinsky's Diabetes Care article. TheraSense manufactures the FreeStyle alternate-site meter, which Koschinsky used for his study.
McGarraugh told Diabetes Health that Koschinsky, in his study, ". did not rub the site before testing, as indicated in the instructions for use." He also points out that Koschinsky used conditions that are "not encountered in real life."
"[He conducted] a glucose-tolerance test without the necessary insulin to control the blood glucose, followed by intravenous insulin to rapdily plunge the subject from hyperglycemia into hypoglycemia," says McGarraugh. "These conditions. exaggerate the fluctuations in blood glucose."
David Horowitz, MD, PhD, vice president of medical and regulatory affairs for LifeScan (which manufactures the One Touch Ultra and FastTake alternate-site meters) agrees with McGarraugh.
"Koschinsky forces extreme fluctuations," says Horowitz. "He began just by giving a glucose-tolerance test, which drove the blood sugar up very fast, and then gave insulin without a meal and drove the blood sugar down very fast. This is something beyond what we do in normal every day life. With these extreme changes he was able to demonstrate, in some cases, significant differences between arm and fingers."
Horowitz says Koschinsky is a good scientist; however, he feels that this test was not demonstrative of the situation people with diabetes ordinarily face.
"His method is a way of doing science. but it is an extreme situation and probably not representative of what a large majority of people with diabetes would see in everyday, normal life."
There's the Rub
In a reply to Koschinsky's study—published in the same issue of Diabetes Care—McGarraugh writes, "The phenomenon they discuss is not a simple function of measurement technology, but a complex function of circulatory physiology."
According to McGarraugh, TheraSense conducted its own study involving 100 subjects with both type 1 and type 2 diabetes, in which blood-sugar measurements from the arm versus the finger were taken at random times throughout the day. McGarraugh says that rubbing the test site reduces arm and finger differences.
"Rubbing the test site vigorously for a few seconds until it feels warm will enhance circulation at the test site," McGarraugh told Diabetes Health. "Blood circulates much faster at the fingertip and palm of the hand than it does in the skin of the arm, leg and abdomen. We believe the faster circulating blood gives the best indication of the glucose level. By increasing circulation at the alternate site, we get a glucose that is closer to the fast-circulating blood at the fingertip."
In the Diabetes Care article, McGarraugh writes that there would be very little difference in therapeutic decisions when the arm (following rubbing), rather than the finger, is used as the test site.
According to McGarraugh, TheraSense has said from the beginning that rubbing the forearm yields the best results. Koschinksy, however, tells Diabetes Health that the rubbing theory does not work sufficiently.
"On average, rubbing can reduce the observed differences [in blood-sugar values] by half, but the success rate can range between zero and 100 percent within the same patient," he says. "The main reason is the poor reproducibility of the rubbing procedure."
A Conflict of Interest?
McGarraugh also points out that Koschinsky did not disclose his affiliation with Roche Diagnostics, a company that does not have an alternate-site testing product.
"[Roche] is losing significant market share to FreeStyle, At Last and One Touch Ultra, which are all alternate-site products," says McGarraugh.
In a letter to the editor that Koschinsky wrote in the September issue of Diabetes Care (Volume 24, number 9, Sept 2001, p. 1697), it is mentioned that Koschinsky and Jungheim receive "research grant support from Roche Diagnostics."
"That's not exactly ’on the payroll,'" says McGarraugh, "but it's a relationship that should be disclosed in publications."
In addition, only one year earlier, Koschinsky presented an abstract study at the ADA scientific sessions in San Antonio, Texas, where he evaluated the same FreeStyle meter. For that study Koschinksy concluded, ". The FreeStyle blood-glucose monitoring system provides accuracy and precision comparable to the best available monitoring systems for self-monitoring of blood glucose."
Koschinsky told Diabetes Health, however, "the San Antonio poster refers to the results obtained at the fingertip."
"At that time we had not performed any alternate-site testing evaluations during fast blood-sugar changes," he says. "The differences observed during fast BG changes between forearm blood sugars and finger blood sugars are not related to accuracy and precision of the glucose monitor used, but to the underlying anatomical and physiological differences of the upper-dermal compartment. We conclude, based on our results, that the observed blood-sugar differences are site specific, but not device specific."
The All-important After-Meal Blood-sugar Reading
In a June study conducted by Roche Diagnostics, researchers Debra Lee, Sandy Weinert and Earl Miller observed 190 people who tested their blood sugar on the finger tips and forearms using the FreeStyle meter. The researchers noted, "In one-hour [after-meal] testing, there is more of a lag phase between forearm and capillary finger stick. The capillary fingerstick is increasing whereas the forearm glucose is not. In this state, there is more variation between forearm and capillary finger stick. The capillary finger stick best mimics the patient's true physiological state."
The researchers add that "Two hours [after a meal], the glucose is stabilizing, so the differences between forearm and capillary finger stick are not large."
McGarraugh responds by saying "One hour [after a meal] is when blood glucose is most likely to be rising rapidly and any difference between arm and finger is at a maximum."
He adds, however, that this is also a time when a person is least likely to be testing their blood-sugar levels.
"It would be inadvisable to make therapeutic judgments on a rapidly changing glucose reading," he says, citing that the American College of Endocrinology recommends after-meal testing "after two hours when readings are more stable."
Don't Test on Alternate Sites When Low
McGarraugh tells Diabetes Health that patients should test on the fingertip when they are testing for hypoglycemia. A spokesperson for TheraSense says changes were made earlier this year and that the company now recommends that when testing for hypoglycemia you should test at the fingertips.
"There is the possibility for a person whose blood glucose is falling rapidly to miss hypoglycemia when testing on the forearm," says McGarraugh. "Although this is not a problem for all people, we recommend that the fingertip be used when testing for hypoglycemia to ensure that hypoglycemia is detected and treated as early as possible. We feel this is the safest, simplest instruction we can give."