Leading Innovations in the Treatment of Juvenile Diabetes
Discovery of Insulin. Frederick Banting and Charles Best discovered the efficacy of treating Juvenile Diabetes with insulin in 1922.
Synthetic Human Insulin. Pure, and without side effects, the first true human insulin was introduced by Eli Lilly in 1982.
Home based blood glucose monitor. Bayer introduced the first home based blood glucose testing system in 1981.
Infusion Pump. MiniMed introduced its first commercial insulin infusion pump in 1983.
Diabetes Control and Complications Trial (“DCCT”). The DCCT Study, completed 1993, determined that tight blood glucose control reduced risk of complications.
Continuous Glucose Monitor. Medtronic introduced the first consumer grade CGM in 2003.
History of Innovations in the Treatment of Juvenile Diabetes
i. Before 1920. The Dark Ages.
ii. 1925 – 1979. The Enlightenment Era.
Because of the impurities and lack of quality of the insulin at this time, the number of injections throughout the day was limited. This was accomplished by adding substances to the insulin formulation that would slow its rate of absorption and prolong its duration. Insulin shots were given only once daily and no distinction was made between a bolus dosage (insulin provided before a meal to reduce the resulting blood glycemic rate) and basal dosage (insulin provided via either long acting insulin or continuous infusion through an insulin pump to provide a continuous baseline level of insulin).
Despite the crude technology and a lack of a reliable glucose measurement system, with the widespread availability of insulin in the late 1920’s, Juvenile Diabetes became a chronic but manageable condition. Even though diabetes had ceased to be a death sentence it remained a considerable foe – as late as the 1950’s twenty percent of diabetics died within twenty years of the disease’s onset. Although not understood at the time, serious complications would become a major health problem for most of the remaining 80% who survived.
In 1942 the American Diabetes Association, an advocacy and sponsor of research, was created. In 1970, the Juvenile Diabetes Research Foundation was created to fund research. The NIDDK Special Diabetes Program (SDP) began funding research in 1998.
iii. 1980 – 1999. The Renaissance Period.
The pace of innovation increased dramatically during this twenty-year period. And innovation was widespread from improvements in the speed and miniaturization of electronics to the dramatic breakthroughs in biotechnology and even included improved education about such simple tasks as “carb counting”. A summary of the major breakthroughs is summarized below.
b. Blood Glucose Measurement.
A blood glucose meter works as follows. The user pricks his finger with a small lancet and places a small amount of blood on a disposable test strip inserted into an electronic meter (typically about the size of a pack of cards). A chemical reaction on the test strip enables the meter to display the resulting blood sugar levels. The resulting measurement is typically expressed in mg/dl with 100 being normal. To put this measurement in context and provide some perspective on how sensitive the human blood supply is to small amounts of sugar consider the following examples. The average human has 5 liters of blood. If one packet of sugar is dissolved in 5 liters of blood, then the resulting concentration of blood sugar is 100 mg/dl; if only a half pack of sugar is dissolved in that same blood supply, then the glycemic index would be only 50 mg/dl, which would be considered hypoglycemic.
Today’s meters are accurate within 5% (which implies that the meter’s reading of 100 would indicate an actual reading of between 95 and 105 which is statistically insignificant for insulin management). Once the blood sample is placed on the strip, the resulting reading is displayed almost immediately. This technology is the predominate means of testing blood sugar today and is widely available, affordable and covered by nearly all insurance plans (including Medicaid and Medicare).
Roche, Abbott, Bayer and J&J are the dominant suppliers of HBGM devices with a reported annual volume of 10 to 15 million units per year in the US. While the original cost of a meter was about $500, today meters are essentially free because the manufactures want to sell the test strips (which range in price up to $1.00 per test strip or $2,200 per year for one who tests his blood sugar six times per day with no waste or errors).
c. Injection Devices.
Insulin Pumps. Commercially available insulin infusion pumps were first introduced in the late 1980’s. This was, in our opinion, one of the most revolutionary changes in the treatment of diabetes since the discovery of insulin and the blood glucose monitor. An insulin infusion pump works as follows. The pump contains a small vial of insulin that is automatically dispensed via a motorized thumbscrew at the bottom of the vial. A modern insulin pump can infuse insulin for three to five days – thus freeing the diabetic from multiple daily injections. Perhaps more importantly the infusion pump supplies a continuous basal rate of insulin while the patient can bolus additional insulin to reduce blood sugar associated with meals and snacks.
Today the physician sets the programing for these devices to best match their care plan. There is a great deal of trial-and-error to get these settings correct. Unfortunately this work to adjust the pump and the associated patient training is rarely reimbursed by insurance companies. While insulin pumps are a dramatic improvement to multiple daily injections, insulin pumps require considerable user involvement. For example, the user inputs his “carb count” and blood sugar levels into the pump and it calculates the bolus infusion for the patient. Insulin pumps can also be adversely impacted by user errors in estimating carb intake or errors from his blood glucose measurement. The result can lead to hypoglycemia or hyperglycemia despite the pump’s advanced features.
e. Carb Counting – Patient Education.
iv. Post 2000. Modern Era – Technological Revolution.
a. Continuous Glucose Monitors.
b. Infusion Pump Improvements
c. Implantable Infusion Pump.
d. The Edmonton Protocol – Islet Cell Transplantation.
The procedure involves recovering islet cells from a cadaver pancreas. The resulting islet cells are infused into the diabetic’s liver through a surgically placed catheter near the portal vein where they can travel to the liver, develop a blood supply and begin producing insulin, partly due to the capability of the liver to regenerate, build new blood vessels and make new supporting tissue when damaged.
Islet cell transplantation has a number of shortcomings that make it unlikely, at least as it is currently implemented, to be a compelling solution for most diabetics.
First, patients are required to use immunosuppressive drugs that have a number of adverse side effects. The immune system is programmed to destroy bacteria, viruses, and tissue it recognizes as “foreign,” including transplanted islets. In addition, the diabetic’s autoimmune response that destroyed transplant recipients’ own islets in the first place can attack the transplanted islets. As a result, immunosuppressive drugs are needed to protect the transplanted islets. These immunosuppressive or anti-rejection medications must be taken for life. These drugs have several adverse side effects including damage to the liver and kidneys, heightened risk of cancer and damage to women’s reproductive abilities.
Second, the cost of islet cell transplant is approximately $140,000 and is not typically covered by insurance. Coverage is generally restricted to those rare diabetics who have become completely insulin intolerant or who have severe and uncontrollable hypoglycemia. Some diabetics are “hypoglycemic unaware” in other words they cannot sense that their blood sugar levels are low or declining rapidly.
Third, the current supply of islet cells is severely limited. Today there are only enough islet cells derived from cadaver pancreases to perform islet cell transplants on 1,500 patients per year.