Diabetes

Part 1

LITTLE BLUE BOOK NO. 875

Edited by E. Haldeman-Julius

Diabetes: Its Cause and Its Treatment With Insulin

Russell M. Wilder, M. D.

With an Introduction by Morris Fishbein, M. D.

HALDEMAN-JULIUS COMPANY GIRARD, KANSAS

LITTLE BLUE BOOK HEALTH SERIES

Edited by

MORRIS FISHBEIN, M. D.

Editor, Journal of the American Medical Association and Associate Editor, Hygeia, a Journal of Individual and Community Health.

Copyright, 1925, Haldeman-Julius Company.

PRINTED IN THE UNITED STATES OF AMERICA

DIABETES: ITS CAUSE AND ITS TREATMENT WITH INSULIN

CONTENTS

Page Introduction 5

The Nature of Diabetes 17

The Story of Insulin 26

The Cause of Diabetes 33

The Diet 45

Treatment in Cases of Mild Diabetes 50

The Treatment of Fevers Occurring in Diabetic Patients 53

Operations on Diabetic Patients 55

Miscellaneous Complications 56

INTRODUCTION

When the scientific body that awards the Nobel prize each year met to consider the award for 1923, there was no question or debate as to the discovery that merited the honor. The prize was granted to Doctors F. G. Banting and J. J. R. MacLeod of Toronto for their work in the discovery of insulin, and each immediately donated one-half the award to colleagues who had shared in this discovery, Doctors C. H. Best and J. B. Collip.

In November, 1920, Dr. Banting, who had returned from war service, was practicing medicine in London, Ontario, and was demonstrating physiology in the medical school of Western University at that place. While reading an article in a surgical magazine, he chanced on a sentence which aroused the train of thought that finally led to his discovery of insulin--a substance that means a longer and more satisfactory life to diabetics.

The article which he read concerned a gland, known as the pancreas, that lies close to the stomach and the upper part of the intestines. This gland is composed of two portions, one of which creates a juice poured into the intestine, which aids in the digestion of food; it is the external secretion and it contains trypsin and two other digestive ferments. The pancreas contains also certain cells which, when seen through the microscope, are marked off from the remaining tissue and which are known by the peculiar name “Islands of Langerhans,” the latter being the name of their discoverer.

Diabetes centuries old.--Now diabetes is no new disease.

Part 2

It was described by Aretaeus, a Greek who lived in the third century, A.D., and hundreds of scientists have worked steadily on the problem ever since that time. Indeed the history of the discovery of insulin is typical of all great medical discoveries of modern times. It represents the summation of a vast amount of knowledge contributed bit by bit by scientists all over the world. When Banting conceived his idea, he took it to Dr. MacLeod, director of physiologic research in the University of Toronto. Professor MacLeod, seeing the possibilities in the investigation, gave him opportunity to work, and provided him with a young assistant, Dr. C. H. Best. The particular problem on which they were to work was the extraction from the pancreas of another secretion, an internal secretion, not poured by the pancreas through a special duct into any other organ or to the exterior, but going instead into the blood stream.

Pancreas yields substance.--Previous investigations had indicated that this secretion was manufactured in the Islands of Langerhans. It was known that when the tube which carries the external secretion--trypsin--was tied, the trypsin would back up into the pancreas, and by its digestive action would destroy the glandular tissue, leaving an organ which consisted chiefly of island tissue.

The investigators did such an operation on a dog. It was also known that an animal might be made diabetic by removing the pancreas; this operation was performed on another dog. Then, when sufficient time had elapsed to permit the breaking down of the pancreas in the first animal, it was painlessly chloroformed, the pancreas removed and an extract made from it. The extract consisted chiefly of island tissue, and this extract was injected into the diabetic dog. The result was the discovery that such injections produced a lower amount of sugar in the dog’s blood and in its urine. This and similar experiments established positively the fact that there was present within the pancreas, and quite certainly in the island tissue chiefly, some substance, not available in the body of the diabetic, which was capable of meeting a deficiency and aiding the diabetic to make proper use of sugar.

Drug dosage and animal experiments.--It now became necessary to devise a method of obtaining the extract in such form as to permit injections into the human being without danger from poisoning by extraneous and unnecessary substances, in other words, a pure product. It also became necessary to devise a method for measuring the dose to be given. How many persons who receive a dose of a medicine realize the amount of investigation necessary to determine these factors? It is necessary to test the effects of a drug on animals before it can be tried on the human being, and it is necessary to study very carefully the changes in the body following the administration of the drug, in order to be certain that no undesirable actions occur.

The Canadian investigators worked in a wholly scientific manner. Their experiments show great attention to the matter of controls. For each animal that was tested, there was a normal animal with which to compare it. The investigators used many dogs, and a vast number of rabbits in making these necessary tests. Not until all the factors of danger had been thoroughly controlled was the drug administered to man. Had it been given without the guiding knowledge obtained by the observations on rabbits, it seems certain that overdoses might have been administered and patients have died.

Overdose of insulin dangerous.--The effects of an overdose of insulin are striking; there is too great a lowering of the amount of sugar, and severe convulsions ensue which may lead to death. Insulin is a powerful remedy; its effects are certain and accurately measurable. If a human being is given too much, his blood sugar falls to a lower concentration. When he gets it around 0.07 per cent he begins to be anxious and nervous about himself. He is likely to become pale, or to flush and perspire profusely. If the blood sugar concentration goes still lower his speech may become disturbed, and he may even manifest mental disturbances. These things too may be prevented, and immediately stopped once they have ensued, by the giving of a small amount of sugar, as for example in the form of four to eight ounces of orange juice. These facts also were discovered by properly conducted experiments.

The investigators now turned their attention to the problem of this disease in human beings, and the results have already been broadcasted through medical periodicals, newspapers and magazines. They are far beyond the early hopes of scientific investigators of the disease. In that terminal stage of diabetes known as coma, when the patient sinks into unconsciousness, insulin seems actually to restore life. Of far greater importance, it offers for the vast majority of diabetics comfort and extended existence. Its administration is closely bound with a knowledge of the food taken into the body, for it is known that a certain amount of insulin will aid the body in handling a certain amount of sugar. When the physician decides to place his patient on the insulin treatment, he usually asks that the patient come into a hospital so that he may first find out the patient’s normal ability to digest sugar, and it is this ability that the physician supplements by the giving of insulin.

Manufacture and sale.--One of the unusual aspects of the insulin discovery was the method of control in its sale. The discoverers did not wish to profit unduly by their work, but they were anxious that its manufacture and application on a large scale be scientifically controlled. Arrangements were therefore made to have it manufactured under accurate supervision in the United States by the Eli Lilly Company, and in Canada by the Connaught Laboratories, and more recently in certain other home and foreign laboratories.

The process of manufacture is an interesting one. The Islands of Langerhans constitute a small portion of what is relatively a small gland. In stock yards and packing houses this gland is called sweet breads; the sweet breads served under glass in the restaurants are usually the pancreas of the sheep or hog, since these are small. The beef pancreas is a much larger organ, weighing about a pound or a pound and a half.

The method devised by Collip for obtaining insulin from the pancreas involves repeated extraction of the ground-up pancreas with alcohol, in order to remove the unnecessary tissue substances. When this is done on a small scale in the chemical laboratory, there is, of course, considerable wastage of raw material and of substances used in the extraction.

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