Some of the research possibilities that might come to fruition (sooner or later) include:

• New tests for insulin resistance: "The Diatest has been utilized in several clinical trials in Canada, 3 of which are completed and have been submitted for publication in peer reviewed journals to complement the study published in Diabetes Care in February 2004. In brief we have investigated the relationship between insulin resistance and endothelial dysfunction, insulin resistance in school children aged 7-18 and correlations with BMI/BP etc." (e-mail from Isodiagnostika inc.) [Added 22Sep2005].

• Better lancing devices: A press release October 26, 2004, from Pelikan Technologies describes a lancing device that would be "the first fully-automated, electronically-controlled, self-contained system that allows a patient to execute the entire lancing process at the touch of a button. Lancing, an often painful act of piercing the skin in order to obtain a sample of blood for glucose measurement, is required multiple times each day for millions of people with diabetes. Pelikan’s innovative technology significantly reduces that pain and allows people with diabetes to more easily obtain a blood sample." This product is expected to be launched in the spring of 2005.

• Insulin patches: There's a very interesting webpage about this topic on the Internet: it's posted by an Israeli teenager, David Rubinstein: "My name is david and i'm 15 years old and 4 years Juvenile diabetic. This system was invented by my father who have many international patents in the drug delivery systems field and who dedicated all his time as well as his staff time to the development of this system. Today the final development of this patented system had some financial problems and I hope my father will find the way to overcome them. After overcoming this problem, the patch can be available in 2 more years..."

  See New Insulin Skin Patch, Purchase puts U of S spin-off company in world leagues , and University of Saskatchewan Spin-Off Set to Become the Site of World Class Drug Delivery Research Centre for recent information about one company's proposed product.

• Pills for Type 1 diabetes: Acarbose (Precose™) might help a bit in theory, but it turns out that it really doesn't do much; insulin's still needed, of course. (Acarbose has been approved by the U.S. FDA for use in Type 2 patients.) Also, see New Drugs for more speculation about oral insulin therapy.

• Buccal (cheek) delivery of insulin: On May 11, 2005, Generex released a a press release that indicates "Oral-lyn™ has been approved for commercial marketing and sale by the Ecuadorian Ministry of Public Health for the treatment of both Type-1 and Type-2 diabetes." But it also adds that "The Company expects to be in a position to commence Phase III clinical trials of Oral-lyn™ in Europe and Canada later this year. " And a reply to an e-mail enquiry indicates that Phase III trial are not in the company's immediate plans. So, one country with a small market and minimal regulatory review of the products' efficacy and safety, but the company still must conduct the large, expensive trials that will allow regulatory approval in the US, Europe, and elsewhere. A press release dated July 14, 1998, from a Canadian company, Generex, discusses "the Company's oral insulin formulation," Oralin, but closer reading indicates it uses a "Metered Dosage Aerosol Applicator". See a more recent webpage about Oralin (http://www.generex.com/nav-noflash/04_oralin_frame.html) from Generex, which states in part: "Oralin is Generex's proprietary insulin formulation, specially engineered to be administered in a convenient new way. The Oralin formulation is delivered directly into the mouth via our RapidMist device, where it's rapidly absorbed into the bloodstream through the buccal mucosa. Oralin is designed to be used in the treatment of both type 1 and type 2 diabetes. People with diabetes can continue to self-administer the insulin doses they need to manage their blood glucose levels - but without needles and without pain." [Updated 12May2005].

• Islet cell transplants: They work to control the blood sugar, and many research centers are working on making them even easier, but many people think the anti-rejection medications are worse than having diabetes! (Of course, pancreas partial transplants have been available for several years. They suffer from the same drawback as mentioned for islet cell transplants: the problem of rejection of the transplanted pancreatic tissue.)

• Minimally-invasive blood sugar testing: MiniMed has submitted FDA Notification on a Continuous Glucose Sensor For Diabetes: "MiniMed's sensor is designed to be inserted into the subcutaneous tissue, usually in the abdominal area, utilizing a soft cannula type device. The physician diagnostic device is to be worn by a patient for three days to gather and store continuous glucose readings that can then be downloaded to a personal computer for analysis. The hypoglycemia alert alarms when the patient's glucose level drops below the limit established by the administering physician. These devices measure glucose levels every 10 seconds and record averages over five minute intervals. After obtaining additional clinical experience with its initial products, MiniMed anticipates filing for FDA clearance for a third system for consumer monitoring which would be designed to replace traditional glucose meters and strips."

  (There was a press release in 1995 discussing this idea; it's available on the internet at KU Researcher Reports on Promising Diabetes Monitor: "LAWRENCE - A promising device for continuously monitoring blood-sugar levels in patients with type I insulin-dependent diabetes was reported Wednesday, Dec. 20, by George Wilson, a University of Kansas researcher. The system could significantly improve the way patients with this form of diabetes monitor their blood-sugar levels and thus reduce the risk of diabetic complications such as retinopathy and kidney failure. Wilson reported on the device at the 1995 International Chemical Congress of the Pacific Basin Societies in Honolulu. In an interview before the meeting, he cautioned that it would be three to five years before the device would be available to the general public. Wilson is Takeru Higuchi distinguished professor of chemistry and pharmaceutical chemistry at KU. The system, developed by Wilson and KU co-workers, centers around a glucose-sensor implant that would continuously monitor blood-sugar levels in diabetics. An alarm warns users of hypoglycemia, a condition when sugar in the blood drops to unsafe levels. So far, the sensor system has proved safe and effective in extensive rat tests at KU and in animal and limited human trials at the Hotel-Dieu Hospital in Paris under the direction of research collaborator Dr. Gérard Reach.")

  I expect MiniMed's device will be approved by the FDA soon. (Update: And it was; see The Continuous Glucose Monitoring System).

• Bloodless blood sugar meters (This section updated 13 April 2001)

  One model, the Diasensor 1000, was presented to the FDA but approval was delayed (in February, 1996). It apparently was planned be available in some non-US countries. In a press release on July 6, 1998, Biocontrol announced that it was preparing to ship the Diasensor 1000 noninvasive glucose sensor to the United Kingdom. On July 2, a related press release said its product received the Conformite Europeenne (CE) Mark approval. At that time, Biocontrol said it plans to resubmit its application to the Food and Drug Administration for approval to market the device in the U.S., and announced its plans to sell the device in the Middle East and elsewhere.

  As of April, 2001, a personal communication to the editor of this website from a type 1 patient in Europe indicated that the writer lived in Europe, and has tried to obtain this device there: "Personally I tried for 3 years to buy a Diasensor from BICO. I also tried to buy it from their European distributor (claiming to sell them!)... It was however always a dead end! Their US-operations explained to clients that they did not yet sell it in the US, and it was a shame that you were not located in Europe, because there they sold it already (when I explained that was very lucky, because I am based in Europe, the phone went dead.) When contacting their European office, the story was reversed. They did no longer sell their Diasensor1000 (which I also earlier tried to buy from both of their sales offices) since they only wanted to give their customers the best, and they had just launched their updated Diasensor2000 on the US-market. When contacting their US office with this reference, they said they were out of stock. When contacting any of the references they mentioned regarding trial/study activities on hospitals, everything ended up in blind alleys..."

  Additionally, there is a recent news article on the Internet that discusses the financial stability of the company, and states in part that "...The Diasensor is a divining rod of sorts for diabetics. Bico promised its 40-pound contraption would conjure a bloodless blood sugar reading, sparing them painful finger pricks. Bico was so confident of the technology that in the early '90s it forecast Diasensor sales of $275 million by 1997. The U.S. Food & Drug Administration twice rejected the Diasensor. European regulators, while sparing their subjects the horrors of hormone-treated beef, have said it's OK for them to buy a Diasensor. Bico said it sold about 10 machines for $427,603 in 1998, but sales fell to $47,500 in 1999 and there were no buyers last year.." (Heard off the Street You can't make this stuff up about Bico, Monday, March 19, 2001 by Len Boselovic, Post-Gazette Staff Writer).

  The company presently states on their website (www.diasensor.com) that "The current design of the Diasensor, which is not yet approved for marketing in the United States by the FDA, incorporates a modem that allows diabetics to transmit glucose readings via the Internet. This permits both a central monitoring department and the diabetic's own physician to monitor glucose levels and assist in glucose control. At this time, the company is working with Joslin Diabetes Center, an affiliate of Harvard Medical School and an international leader in diabetes treatment, to conduct FDA-approved clinical trials on the Diasensor in the U.S."

  See Non-invasive Blood Glucose Meters at Children with Diabetes, and The Waiting Game: The day has yet to dawn on pain-free blood glucose tests. But it's coming, in the June 1998 issue of Diabetes Forecast, for more information about non-invasive and minimally-invasive glucose testing.

• Inhaled insulin, by aerosol delivery device: For additional information, see Inhaled Insulin for updated information.

  Two abstracts* (which appear to have been written by the same person!) were presented on June 16, 1998 at the of the 58th Scientific Sessions of the American Diabetes Association. The first was entitled "Treatment of Type 2 Diabetes Mellitus With Inhaled Human Insulin: A 3-Month, Multicenter Trial" It was by William T. Cefalu, et al. In it, the authors comment:

  "...INH [inhaled insulin] was very well tolerated... Satisfaction questionnaire results favored INH, and 92% of INH patients opted for 1-yr extension of INH therapy. We conclude that anI [insulin] regimen using INH represents a well tolerated and comparably effective alternative to a conventional regimen using regular SC I [subcutaneous injections of insulin] in management of NIDDM, and that INH is liked by patients."

  The second abstract, also presented on June 16, was entitled "Treatment of Type 1 Diabetes Mellitus With Inhaled Human Insulin: A 3-Month, Multicenter Trial." Its lead author was Jay S. Skyler. The abstract states:

  "A new dry powder I formulation and aerosol delivery device permits reproducible pulmonary delivery of rapid-acting I in therapeutic amounts with 1-2 inhalations per dose. To compare the safety and efficacy of a regimen using this inhaled I (INH) vs. a conventional injection regimen (SC), 70 patients with type 1 diabetes (IDDM) from 10 study sites were randomized, after a 1-mo run-in period, to either INH or SC (n=35 ea) treatment for 3 mo. SC continued their pre-study I regimen (2-3 injections/day), while INH received pre-meal INH plus a bedtime Ultralente I injection... INH was very well tolerated... Satisfaction questionnaire results favored INH, and 80% of INH patients opted for 1-yr extension of INH therapy. We conclude that an I regimen using INH offers a well tolerated and comparably effective alternative to a conventional regimen using regular SC I in management of IDDM, and that INH is liked by patients."

   *  The information presented in "abstract form," as these brief medical papers are called, is often somewhat sketchy, and less scientifically critiqued, compared to reports that are published as scientific articles in medical journals. The process of publication of a paper as a scientific article is subject to thevery time-consuming process of being thoroughly peer-reviewed, and can take months or years. Thus, abstracts are a way to present new information rapidly. The information presented in abstract form is usually considered as being probably valid; frequently, publication of the same information occurs in expanded, peer-reviewed form a few months or years later.

  In an article in the Kansas City Star on June 17, by Thomas H Maugh II of the Los Angeles Times, he indicates that "the new system [was] developed by Inhaled [sic] Therapeutic Systems of San Carlos, California" (see below). Mr. Maugh also states "people intrested in participating in the study can volunteer by calling (800) 438-1985 (which is Pfizer Medical Information, and is answered between 8:45 AM and 5 PM, Monday - Friday, Eastern Time). (Information added to the Diabetes Monitor on June 17, 1998).

  There's a recent announcement (1997) from Inhale Therapeutic Systems that "Pfizer announces at Analyst Meeting that pulmonary insulin is providing virtually identical control to subcutaneous injection in three-month trials with Type I and Type II diabetics." According to ITS, Pfizer and ITS are in Phase II trials of using inhaled insulin. (as of January, 1998). (It appears that the two trials announced above are those mentioned in this earlier press release. June 17, 1998)

• Inhaled insulin, by nasal spray:

  It's been tried, but half the patients didn't want to stay on it during a three-month study that was published a few years ago.

  Another company is trying again: in an October, 2004 press release, Bentley Pharmaceuticals, Inc. discussed an exploratory Phase I study to examine Bentley’s intranasal insulin formulation; it demonstrated rapid onset of action and appropriate duration of action for potential use, but there's little information on how well it was tolerated (except a very broad statement that it was "generally well tolerated").

• Protected insertion of living islands of Langerhans tissue: Islet Sheet Medical is working on a "thin sheet bio-artificial pancreas containing islets of Langerhans for treatment of insulin-requiring diabetes... Like other bio-artificial devices, ISM's bio-artificial pancreas is a hybrid of living cells (insulin-producing islets of Langerhans) and a polymer matrix coating that protects the living cells. It responds to changes in blood sugar by secreting hormones just like the native pancreas. It will normalize blood sugars using normal physiology and will eliminate the vascular complications of diabetes. Life expectancy for diabetics so treated will increase to nearly that of nondiabetics and the cost of health care of treated diabetics will decrease..." That's a lot of hype for a product that hasn't yet been tried in humans, but the concept is certainly intriguing. (May 29, 1998.)