Ninety Years of Insulin Therapy   (January 8, 2012))

A recent article in the Toronto Star, Miracle on Bloor Street, reminded me that insulin therapy's 90th birthday will be arriving this week. Leonard Thompson, a 14-year-old teenager who had lost weight to 65 pounds, received his first injection in Toronto, Canada on January 11, 1922. He dramatically improved, and went on to live thirteen more years, dying at age 27 of pneumonia contracted after a motorcycle accident. (I have been unable to identify if the accident was in any way associated with hypoglycemia or other diabetes issues.)

Another success story from the early days of insulin therapy involves a young woman, Elizabeth Hughes. Elizabeth, like Leonard, was dying of diabetes before getting her first insulin injections in 1922. After a long and fulfilling life, she died in 1981 at age 73. It's been estimated that she received 42,000 insulin injections over her lifetime.

There are many more such stories from the early days, and many are summarized in a book which I strongly recommend that the interested reader locate and read: The Discovery of Insulin by Michael Bliss. (An excerpt from the book is available to peruse at Amazon.com.) Dr. Bliss, a Canadian historian who has written on several medical topics, wrote The Discovery of Insulin in 1982, and has lectured on the subject of the discovery of insulin many times. I have read and reread his book several times, and heard his presentation three times, and it's heartwarming to hear it every time.

The story of the discovery of insulin is also a story about scientific trial and error, and about scientific politics: the principal codevelopers of insulin included four men (Frederick Grant Banting, Charles Herbert Best, James Bertram Collip, and John James Rickard Macleod), of which two shared the 1923 Nobel Prize for Medicine: the prize was awarded to Banting and  Macleod "for the discovery of insulin". In many people's minds, Banting deserved recognition as well, and the choice of Macleod as co-winner was controversial. Banting decided to share the prize and gave half his prize money to Best. Macleod, in turn, split his half with Collip.

It's fascinating to read from Banting's Nobel Lecture (his acceptance speech) what the first patients went through as part of the clinical trial:

"In general the routine followed in all these clinics was as follows.

"After a careful history had been taken, the patient was given a complete physical examination... [Lab tests included] daily routine urinalysis [which] included the volume of the twenty-four hour specimen, the specific gravity, the reaction, and tests for albumen...acetone bodies... [and] sugar determinations... In addition to the above, the blood sugars were estimated...

"At first the patient continued on the same diet as that previous to his admission to hospital in order to obtain some idea of the severity of his case, and to avoid complications from sudden change of diet... On the second or third day he was placed upon a diet, the caloric value of which was calculated on his basal requirement... The patient remained on this basal requirement diet at least a week. During this time, blood sugar was estimated before, and three hours after, breakfast, in order to determine the fasting level and the effect of food. The quantity of sugar excreted was estimated daily...

"If a patient remained sugar-free and had a normal blood sugar when on a diet containing five hundred calories above his basal requirement he was not considered sufficiently severe for insulin treatment... If, however, he was unable to metabolize this amount, insulin treatment was commenced...

"In severe cases insulin was administered subcutaneously three times a day, from one-half to three-quarters of an hour before meals. This was done so that the curve of hypoglycaemia produced by the insulin was superimposed on the curve of hyperglycaemia produced by the meal. In rare cases a small fourth dose was given at bed time to control nocturnal glycosuria. The less severe cases could be satisfactorily treated on a morning and evening dose or a single dose before breakfast.

"When the insulin treatment was established, if sugar was present in the twenty-four hour specimen of urine, the dosage was gradually raised till the patient became sugar-free. If he was not receiving sufficient food for maintenance, diet and dosage of insulin were gradually raised. If small quantities of urinary sugar persist, it was desirable to find out at what period of the day this was excreted. In order to do this, each specimen in the twenty-four hours was analysed separately. An increase in the dose previous to the appearance of glycosuria will prevent its occurrence.

"In severe cases it was found preferable to give the largest dose of insulin in the morning, and reduced doses throughout the day. For example, a patient may receive fifteen units in the morning, ten units at noon, and ten units at night. If three equal doses are given there may be morning glycosuria and evening hypoglycaemia, whereas the extremes of blood sugar causing these conditions may be prevented by the above distribution."

Ninety years later, we follow the exact same logic to obtain tight control of hyperglycemia: use multiple injections of insulin personalized to the blood sugar levels (and carb content of the meals to be eaten). Of course, we have a few additional tools, such as insulin pumps and continuous glucose monitors, to help, and don't need to do 24-hour urine glucose determinations on a daily basis!

I wonder what the 100^th year of diabetes therapy will be like --  just 10 more years to go.