Diabetes Technology Meeting – Trip Report

San Francisco, CA

November 2 & 3, 2001

Attended by C. S. Tritt, Ph.D.

Sponsored by the Dorothy L. and James E. Frank Diabetes Research Institute

This was one of the best scientific meetings I have ever attended. Speakers and attendees were a mix of industrial, academic and clinical researchers from the U.S. and around the world. The technical level of the presentation was very appropriate (high but not extreme). There seems to be continued progress on both non-invasive plasma glucose monitoring and alternatives to subcutaneous insulin injection. However, no specific technologies or products appear have definitive advantages over their competitors. Most appear to require significant additional development.

The only really new technique I discovered at the meeting was the use of the Clarke Error Grid in the evaluation of identity plots. I was not familiar with this technique and yet it was used in nearly all the presentations involving new in vivo glucose measurement techniques. I think this is a topic that should be included in our statistics courses, if it not already. I also learned that there is a consortium, ADICOL, in Europe doing a lot of interesting diabetes device research and development. The CDC also has a number of ongoing projects (www.cdc.gov/diabetes/projects/ndl.html).

The key current need in diabetes treatment involves tighter regulation of plasma glucose level while minimizing the risk of hypoglycemia. More comfortable and convenient glucose concentration monitoring and insulin delivery are critical to achieving this level of control. This is particularly true for Type II diabetes for psychological reasons. It was noted that many Type II diabetics should and probably will go on insulin therapy.

A number of new glucose monitoring systems were described, including the Biostator™ blood, the GlucoWatch™ transdermal, SpectRx™ microportation/ISF and Diasensor™ devices. Several photometric methods were described for in vivo glucose monitoring. Most are based on IR spectrophotometry (in both the combination and overtone bands) and Partial Least Squares (PLS) Multiple Linear Regression (MLR) approaches. However, Raman, polarimetric, RF and fluorescence methods were also described in presentations and posters. A number of variations on amperemetric glucose electrodes (the good old Pt electrode, glucose oxidase, hydrogen peroxide method) were described including implantable and microneedle sensors (including one by iSense Corp.). A novel system involving the measurement glucose dependent viscosity changes in a solution being pumped through a microdialysis needle was described. The use of microdialysis in the physiological study of tissue response to injury and implantation was also described. Laser, ultrasonic and microprojectile methods were described for increasing skin permeability with the intent of extracting interstitial fluid for glucose analysis. Finally, the point was made that the eye is not only a window to the soul but also a window to the body. A number of the photometric glucose analysis methods involved making measurement on ocular tissues.

A number of new approaches to insulin administration were described, including a modified MiniMed™ implantable pump with an attached glucose sensor. Much work is being done on implantable pump-sensor combinations for closed loop control with some limited clinical trail data being reported. Several approaches to closed loop were described, but simple PID control seemed sufficient in early studies. Two presentations described micro-electro-mechanical systems (MEMS). One covered the microchip device for possible long-term (1 year) daily insulin administration and the other covered MEM pumps, valves and mixing devices. A number of alternate routes for insulin delivery were also described including inhalation of liquid (AERx™) and particulate aerosols and modified insulin for oral/GI delivery. The particulate aerosol device, Exubera™, was interesting in that it was completely mechanical.

NASA researchers reported the need to better understand the physiology of long-term space flight (it appears to mimic aging with decreased glucose tolerance, alterations in amino acid metabolism and bone loss), simplification and miniaturization of physiological instrumentation and cell culture in simulated microgravity devices.

I continue to be amazed at the complexity and subtlety of cell biology and the immune system. Several islet cell transplant and culture studies were described. With current protocols, transplant success rates are still relatively low. However, they are improving. Islet cell culture prior to implantation appears to reduce their immunigenicity. There were some concerns reported about the immunigenicity of the new insulins and insulin delivery methods. However, it appears that these concerns will only be resolved through long-term clinical studies with careful surveillance. Tissue engineering was discussed in the context of cell culture techniques and controlling the tissue reaction (including enhancing neomicrovascularization) near implanted sensors. The supply of donor organs will continue to limit the number of islet cell transplant unless cell culture techniques can be found to expand or differentiate islet cells.

I also noted that there appears to be a number of industrial research opportunities in diabetes related area for MSOE’s Physics and Chemistry Department. This might provide an alternative to the creation of pre-med or chemistry minors at MSOE.