HISTORICAL FEATURE

An occasional series about historical aspects of diabetes

Diets and the discovery of insulin Graham Beer, Metabolic Marketing Department, Bayer plc,Newbury, UK

The starvation diet Before the discovery of insulin (in 1921) the main method of treatment of diabetes was starvation, as popularised by Dr Frederick Allen around the turn of this century. The average life expec- tancy of patients on The Allen Diet was three to four years, and they generally died of starvation rather than diabetes. Allen was the first to admit this, but usually pinned the blame on previous doctors for being too soft-hearted: ‘anyone making use of high carbo- hydrate, protein or fat diets for the sake of supposed comfort must be prepared to assume responsibility for occasional blindness and similar troubles’.

Initially he put patients on a strict fast for up to ten days until the sugar dis- appeared from their urine. Low calorie foods - such as thrice-cooked veget- ables - were then cautiously re-intro- duced. As soon as glucose appeared in the urine, fasting was begun again. During periods of feeding, only 410% of energy was derived from carbo- hydrate, with 72-79% coming from fat.

Not surprisingly, this regimen placed an intense burden on patients. Allen’s own case histories, for example, in- clude that of a 12 year old boy who supplemented his meagre diet while in hospital by whatever he could get his hands on: ’among the unusual things eaten were toothpaste and bird seed, the latter being obtained from the cage of a canary which he had asked for’. This rebelliousness caused Allen much annoy- ance and when the boy finally died of starvation, weighing less than 40 pounds, Allen maintained that the ‘real trouble was the unusual ingenuity of the patient in obtaining forbidden food‘.

The boy’s ravenous appetite was put to good use when Allen experimented with feeding him raw pancreas, later con- cluding that the therapy had no value whatsoever.

Wartime diet The French physician Bouchardat was the first person to note that the incidence and severity of non-insulin-dependent did- betes plummets during times of war and famine. He made his observation during

Figurn 7. Paracelsus (1493-154 1) evaporated the family and adjusting their treatment urine of his diabetic patients and found the ‘salt’ was accordingly, sugar. His practice of drinking the blood of his diabeticpatients enabled him to observe and describe hyperglycaemia first-hand

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the siege of Paris in 1871. After defeat in the Franco-Prussion War, French extre- mists took refuge in Paris. The legal government of France laid siege to the city for 73 days, during which time some 20,000 Parisians were killed. Food was in short supply and was strictly rationed.

Bouchardat was also the first person to introduce regular self-monitoring of glu- cose in urine and he made the first description of diabetic retinopathy.

In this century, during the First and Second World Wars, the death rate of people with diabetes plummeted, corre- lating closely with periods of food ration- ing, This effect seemed to be confined to non-insulin-dependent diabetics. The Second World War revolutionised the whole concept of diabetic diet. Before the war, newly diagnosed diabetics were given a rigid diet sheet and many people stuck to the same menu day after day. With rationing this was no longer feasible, and for the first time people with diabetes were eating the same as the rest of the

The importance of the pancreas Matthew Dobson was a brilliant phy- sician working at the Liverpool Infir- mary. He repeated Paracelsus’s experi- ment from the 16th century of evapora- ting down urine, and showed that the ‘salt’ left behind was sugar (Fzgure I). The unwholesome practice o f drinking the blood of his patients had given Paracelsus the distinction of being the first person to observe hyperglycaemia.

The English physician, Thomas Cawley, was the first person to connect diabetes with lesions in the pancreas. Until then, diabetes had been often viewed as a disease of the stomach. During a post-mortem in 1788 he noticed that the pancreas was ‘full of calculi, which were firmly impacted in its substance. They were of various sizes, not exceeding that of a pea, white, and made up of a number of lesser ones which made their surface rough, like mulberry stones’.

The following century, the great physiologist, Claude Bernard, dis-

covered that sugar was stored in the liver as glycogen, and could be released into the blood from this store when required.

A few years later, in 1899, the Gennan physiologists, Oscar Minkowski and Jospeh von Mering, did work which pointed to the existence of an internal secretion in the pancreas. They dis- covered, while investigating fat digestion, that removal of the pancreas causes acute, permanent diabetes.

Minkowski had previously investigated the biochemical nature of diabetes and determined in 1884 that beta-hydroxy- butyric acid, with a reduction in blood bicarbonate, underlay the phenomenon of diabetic acidosis.

Twenty years earlier the German phy- sician, Paul Langerhans, had described the islets of endocrine tissue in the pan- creas that are named after him. Following Minkowski and von Mering’s discoveries, workers in the field were quick to focus on these as the likely source of the antidiabetic principle. Opie in the USA

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HISTORICAL FEATURE Diets and the ciiscove y of insulin

and Sobolew in Russia soon demon- strated pathological changes in the islets of human diabetics at autopsy.

In 1909 PA Meyer prophetically named the elusive substance ‘insulin’ from the Latin, insulae or islets.

The discovery of insulin The American physiologist, EL Scott, came very near to discovering insulin in 1912, failing only in that he used alcohol as the extraction medium (insulin being insoluble in alcohol).

Following on from Scott’s work, Fred- erick Banting, the Canadian orthopaedic surgeon and Charles Rest, then a medical student, were given eight weeks in which to test Banting’s hypothesis that effective extraction from the pancreaas might be prevented by the digestive enzymes origi- nating in the pancreatic acinar tissues.

Figure 2. Banting (right) and Best (left) in their laboratory working on pancreas extractions. They shared the Nobel Prize for Medicine in 1923 for their extraction and use of insulin to treat diabetes

They first ligated the pancreatic ducts (causing atrophy of the exocrine tissue) then suspended the tissue in Ringer’s solution at low temperatures (Figure2).

The ground-up extract was injected into a comatose dog named Marjorie. She recovered consciousness to become the first animal to receive insulin. The first person to receive insulin was 14 year old Leonard Thompson who inade a remark- able recovery after starting insulin therapy on 11 January 1922 (see also Figure 3). Banting won the Nobel Prize for Medicine in 1923 jointly with Professor JJK Macleod and shared his prize with his student co- worker.

The formation of the British Diabetic Association HD Lawrence was one of the greatest names in 20th century diabetology. He

began his distinguished career at King’s College Hospital where, as second House Surgeon, he was diagnosed as diabetic in 1921. This was before the advent of insu- lin. In 1921 he published Food Tables in order to provide a varied yet accurate diet for diabetics. The guiding principle was carbohydrate restriction, the caloric bal- ance being made up by a high intake of fat.

Later, in 1925, he developed the more complex ‘line ration scheme’. These were later known as ‘carbohydrate exchanges’ and really came into their own with rationing in World War 11.

Lawrence is probably best known as joint founder of the British Diabetic Association with HG Wells (Figure 4). In 1933 Lawrence appealed to some of his private patients for funds to set up a new diabetes department at King’s. Among these was Wells, who offered to write a letter to 7he Times. There was a huge response - so much so, that Wells wrote again the following year to publicise the newly formed Diabetic Assocation. This was to be the first patient-oriented associ- ation in the UK.

EDITORS’ NOTES (i) Thisarticle is based on original research

carried out in the preparation of the “History of Diabetes” Fxhibition, com-

piled and sponsored by Bayer plc. The Exhibition formed part of a series of education meetings which touwd the UK andEurope, aiming to raiseawarenessof non-insulin-dependent diabetes and including presentations from leading diabetes specialists.

( i i ) ‘fie BDA Careline (Tel 01 71 636 61 12) is operational Mon-Fri, 9am-5pm.

Figure 3. The clinicalpicture of Type 1 diabetes in the pre-insulin era (left). The same patient, one of the first to receive the newly available insulin, in 1922 (right) (right)

Figure 4. Co-founders of the British Diabetic Association, the author HG Wells (left) and the distinguished diabetologist RD Lawrence

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