Before the discovery of insulin (1921), people with diabetes were doomed to die. Its discovery, due to the beautiful collaboration of F. MacLeod, has since worked miracles in saving thousands of people across the world from certain death.

Since ancient times, the Greeks and Egyptians knew about diabetes. The word diabetes even comes from the Greek “to pass through”, a term which refers to the sugary urine observed by the Greeks in certain patients.

Insulin is a protein made and secreted by the beta cells of the islet of Langerhans in the pancreas. To keep it simple and short (the idea is not to give you a physiology class): insulin is the key that allows glucose (sugar) to pass from our our blood to our cells. Without this key, the glucose remains in the blood; and the cells, and consequently our body, lack energy. They therefore draw the energy to function from where they can, namely fat. All this explains the main symptoms of the onset of type 1 diabetes: intense thirst (to dilute the excess sugars in our blood), frequent urination, weight loss (we draw our energy from fat), and tiredness.

As type 1 diabetes is caused by a dysfunction in the production of insulin, it is vital that people who suffer from the disease administer it through daily injections. However, physiological insulin requirements vary throughout the day, and whether or not the person have diabetes.

For people with type 1 diabetics, finding the right basal insulin doses (basic insulin requirements) is the first challenge. Continuous glucose measurement (CGM) is a valuable aid for this 1st mission. To this 1st challenge is added the patient’s lifestyle: whether he or she exercise, his or her diet and his or her stress level, which can cause different levels of blood sugar.

The history of insulin

• January 11, 1922 – The first injection of insulin to man. The first injections of pancreatic extracts save Leonard Thompson, a 14-year-old boy who had fallen into a coma due to diabetes.
• 1923 – The Nobel Prize in Medicine is awarded to Banting and Mac Leod. Banting shares it with Best, Mac Leod with Collip. That same year, laboratories began producing insulin from the pancreas of beef and pork, which has insulin very similar to that of humans.
• 1935 – Hagedorn and Fisher developed Protamine Zinc insulin, the first slow-acting insulin.
• Development and marketing in the 1950s of Neutral Protamine Hagedorn, an intermediate-acting insulin still widely used today under the name NPH.
• 1978 – Eli Lilly Laboratories successfully clones the human insulin gene, an important step in the production of insulin by genetic engineering.
• 1980 – Pork insulin is humanized by changing the only amino acid that distinguishes it from human insulin.
• 1982 – The first human insulin obtained by genetic engineering appears on the market. Unlike insulins extracted from animal pancreas, this is truly human insulin.
• 1986 – Novo Laboratories chooses the yeast Saccharomyces cerevisiae over E. coli to express the human insulin gene and obtain the hormone industrially.

Consequences of a lack of insulin

Immediate consequences

• Blood sugar increases abnormally: the blood therefore becomes sweeter, and therefore more concentrated. To dilute this excess glucose, the person will drink a lot of water. And since he or she drinks a lot, he or she urinates a lot. Drinking more than 3 liters a day and urinating as much are the first signs, what doctors call polyuria-polydipsia.
• All this excess glucose in the blood will have to be eliminated in the urine: the urine becomes sweet, which doctors measure in glycosuria, which promotes urinary tract infections because the microbes find in the urine a favorable environment for their development. This is a sometimes revealing sign: repeated urinary tract infections.

All this generally takes place quietly and over several years. This is true for diabetes 2. On the other hand, for type 1 diabetes, which is due to insufficient insulin secretion, the onset is generally sudden and can start in adolescence. If we are not careful, diabetic disease will set in with long term consequences.

Long-term consequences

• This excess glucose in the blood will gradually attack the walls of the small arteries in the body called arterioles. And we have arterioles everywhere: in the kidney, in the brain, in the heart, in the retina, in the muscles etc. There is therefore a risk of developing little by little diabetic arterial disease, and therefore poor vascularization of the organs in question.
• The arteries of the kidney will suffer and give rise to glomerulonephritis.
• The retina will deteriorate which will lead to retinopathy.
• The arteries of the heart will be damaged which causes atherosclerosis and which explains why diabetes is one of the cardiovascular risk factors.
• The arteries of the lower limbs will gradually become blocked, which in the very long term risks causing gangrene localized especially in the feet: plantar perforating disease.
• Blood also circulates less well in the arteries of the skin, which causes localized infections (tendency to form abscesses or boils).
• The nerves and the nervous system in general are affected, which is the cause of polyneuritis.

Acid-ketosis coma

This is the serious accident. It threatens as much the person who leaves all these signs behind for years as the one who does not take or who takes his treatment badly.

Insulin helps sugar to enter cells (liver, muscles, heart in particular), they will on the other hand lack glucose which is their main fuel. This can therefore lead to temporary discomfort or weakness.

To find the energy essential to make the cells function, they will destroy fat to transform them into glucose. But this transformation has a price: the formation of acetone, which will also be found in the urine. Having acetone in the urine (acetonuria) does not in itself matter, but this acetone is also found in the blood, which is toxic to the brain and acidifies the blood. This phenomenon, called ketoacidosis, will cause nausea, vomiting, an acetonic odor in the breath (a bit like the smell of nail polish thinner), and disturbances of consciousness which can go as far as coma. As all the absorbed water is eliminated, vomiting eventually causes dehydration.