University of Michigan
Department of Pediatrics
Evidence-Based Pediatrics Web Site

Question

• A 13 year-old patient with type I diabetes mellitus presents to the pediatric endocrine clinic. His parents report that he refuses to do blood sugar measurements due to a needle phobia. They have heard about a "watch" which monitors blood sugar without needles and wonder how accurate is it?

Clinical Bottom Lines

1. All studies evaluating iontophoresis have been done in the adult population.
2. More than 96% of the measurements obtained by iontophoresis fall in the range of therapeutic relevance.
3. The most important aspect of blood glucose monitoring is the accuracy in reading low glucose values.  Iontophoresis shows the lowest variation at blood glucose below 70 mg/d.
4. Iontophoresis compares to published results analyzing commercially available self-monitoring blood glucose devices.
5. The lag time required to obtain readings through iontophoresis may be dangerous in the context of rapidly falling blood sugars.
6. Skin irritation at the site of iontophoresis occurs.

Summary of Key Evidence

1. 92 subjects with type 1 or 2 diabetes requiring insulin therapy wore a total of 155 biographers (63 subjects wore 2 devices) on their forearms. All subjects were aged 18 years or older (mean 42.1 years with SD 15.1 years); 59.8% were women and consisted of a broad ethnic cross section.¹
2. Up to 3 biographer measurements were obtained per hour in addition to 2 finger stick capillary blood samples, whose blood sugar content was determined by a commercially available monitor. Measurements were done over 12 hours, yielding a maximum of 23 paired measurements.
3. Of 2507 possible data pairs, 153 were lost due to biographer shutoff or missing BG values. Another 187 (7.9%) were skipped by the predetermined threshold screens which monitor skin conductance and temperature.
4. A Clarke error grid was then used to assess clinical significance, as a function of blood glucose range. For all 2167 data pairs, the mean error (ME) was -1mg/dl with a SD of 33 mg/dl. The MEs and SDs were then provided by glucose ranges with MEs ranging 0.54 to 12 mg/dl and SDs from 17.46 to 46.98 mg/dl.

Additional Comments

• Tight glucose control, using frequent glucose measurements to guide the administration of insulin decrease the long-term complications of diabetes but with a threefold increase in hypoglycemic events.²
• An automatic system could provide detailed information on glucose patterns and trends in addition to an opportunity to sound alarms for rapid declines in blood glucose values to reduce the risk of hypoglycemic events.
• Iontophoresis is a technique where a constant low-level of electricity is conducted through the skin between an anode and a cathode. Positive particles (ions) are attracted to the cathode. Uncharged particles, such as glucose are carried along with the ions by convective transport. As the skin has a negative charge at neutral pH, there is a greater net transport to the cathode.
• At the cathode, glucose is broken down by glucose oxidase which causes the oxidation of glucose to gluconic acid and hydrogen peroxide. The hydrogen peroxide is then detected by its breakdown via an electrocatalytic oxidation reaction to O₂ + 2H⁺ + 2 electrons.
• The entire process takes 10 minutes: 3 minutes to collect glucose and 7 minutes for the sensing mechanism to ensure all glucose, and subsequently hydrogen peroxide, are consumed.
• Iontophoresis may be a superior choice to self-monitoring blood glucose devices since it avoids large proteins, e.g. hemoglobin, which can currently cause interference.  The technique monitors peripheral tissue where blood glucose utilization actually occurs.
• Other studies have shown that iontophoresis has produced acceptable results for 95% of its measurements, comparable to that of currently available blood glucose monitors.
• Other noninvasive techniques for blood glucose monitoring include Far-infrared radiation, near-infrared radiation, radiowave impedance, optical rotation of polarized light, and interstitial fluid harvesting.
  
  

   

Citation

1. Tamada JA, et al.  Noninvasive glucose monitoring: Comprehensive clinical results.  Cygnus Research Team.  Journal of the American Medical Association, 1999; 282(19):1839-44.
2. The Diabetes Control and Complication Trial Research Group.  The effect of intensive treatment of diabetes on the development and progression of long-term complications of insulin-dependent diabetes mellitus.  The New England Journal of Medicine, 1993; 329:997-1036.
3. Tamada JA, Bohannon NJV, Potts RO.  Measurement of glucose in diabetic subjects using noninvasive transdermal extraction.  Nature Medical, 1995; 1:1198-1201.

CAT Author: John Schmidt, MD

CAT Appraisers: John Frohna, MD

Date appraised: March 6, 2000