Sub Navigation
The Story Behind: Insulin Detemir
Désolé. Actuellement, cette page n'existe pas en français.
A puzzling search for causes
Diabetes mellitus is marked either by the body's failure to produce insulin altogether (type I diabetes), or by mismanagement of the hormone for regulating blood sugar levels (type II diabetes). Although diabetes has been known for thousands of years - it was first recorded in Egypt in the year 1552 BC during the 3rd Dynasty - the metabolic processes, and the role of insulin, behind the disease re-mained veiled in mystery for several thousand years.
In the 1st century AD, the Greek scholar Arateus described diabetes as "the melting down of flesh and limbs into urine," since the disease is marked by frequent urination. Consequently, the Greek physi-cian Galen of Pergamum assumed diabetes to be an ailment of the kidneys - a misconception that remained common wisdom among scholars until the end of the 19th century.
Nevertheless, the role of sugar in the disease was known at an early stage, reflected in the Latin "mel-litus" (honey) used in describing the disorder. Chemical tests for detecting sugar levels in urine were developed in the early 19th century, while the causes of diabetes still remained unclear.
A metabolic mystery
When medical student Paul Langerhans pointed his microscope at the structure of the human pan-creas in his Berlin laboratory in 1869, he marvelled at a number of previously unnoticed tissue clumps within the small organ. But although Langerhans and his son, Archibald, suspected the secretions of these "Islets of Langerhans" to have a regulatory role on the metabolism, their exact physiological function remained beyond their reach.
Another piece of the puzzle would be needed to form a coherent picture. In 1889, the Polish-German physician Oskar Minkowski together with Joseph von Mering conducted a groundbreaking animal ex-periment. The two scientists removed the pancreas of a healthy dog, only to discover an extraordinarily high sugar content in the dog's urine. For the first time, here was proof of the direct link between diabetes and the pancreas.
Completing the overall picture, American biologist Eugene L. Opie in 1901 demonstrated that the ab-sence of a hormone named "insulin" - a term derived from its origin in the pancreatic Islets of Langerhans - was the source of diabetes. Insulin is a peptide hormone released to inform or "signal" the body's cells of the intake of food, causing liver and muscle cells to take in glucose and fat cells to take in blood lipids. Without the hormone, cell activity may not be triggered, causing a critical, if not fatal, climb in blood sugar levels.
Early treatments
The first scientist to successfully isolate insulin in the laboratory in concentrated form was Nicolae Paulescu at the University of Bucharest, who called it "pancreatine" in 1921. Scientists soon found that insulin was present in all animals, and that some species in fact produced insulin that could trigger responses in the human metabolism as well, including pigs, cows and dogs.
In 1922, a team at Toronto General Hospital including Frederick Banting, Charles Best, James Collip and J.J.R. Macleod performed the first clinical trials using insulin derived from a foetal calf pancreas. Eventually, they were successful in reducing the symptoms of their 14-year-old patient. Motivated by the success, they took the treatment to other, often comatose, patients in the diabetes ward and were able to bring previously hopeless cases back within a matter of minutes. In 1923, Banting and Mac-leod received the Nobel Prize for their achievement.
That same year, the drug manufacturer Ely Lilly and Company began selling commercially produced insulin derived from cows. Other drug makers followed suit and insulin extracted from the pancreata of cows, horses, pigs and fish entered into clinical practice. The purity of insulin was problematic at first, causing heavy allergic reactions in some patients.
However, the purity of insulin drastically improved over the years, mostly thanks to the development of synthetic "human" insulin by American pharmaceutical company Genentech in 1978, first marketed by Eli Lilly as Humulin in 1982. Synthetic insulin is produced by inserting human DNA into host cells, mostly E. coli or other bacteria, in specially designed DNA expression vectors. The expression vectors are then "activated," thereby inducing the bacteria's cellular machinery to make human insulin, which may then be isolated and purified. Today, almost all insulin products available on the world market are synthetic "human" insulin or their analogues; animal insulin products have been widely phased out.
Leaps and bounds
Despite these advancements, insulin therapy left much to be desired. Until recently, patients de-pended on constant monitoring of blood sugar levels and regular injections several times a day, since insulin is broken down rapidly in the blood stream after fulfilling its signalling function. Additional short-comings in clinical practice included sudden spikes in blood sugar levels in some patients, and a high incidence of weight gain during treatment.
In response to these issues, the inventors at Novo Nordisk created a long-acting synthetic human insulin analogue by combining the hormone with a 6-24-carbon fatty acid moiety, slowing the meta-bolic breakdown significantly. The fatty acid modification allows the new, so called "insulin detemir" to reversibly bind to albumin in the blood serum, thereby providing slow absorption of up to 24 hours in patients with either type 1 or type 2 diabetes mellitus at a lowered risk of weight gain.
The new insulin was launched in the United States under the name Levemir on 27 March 2006 and has brought a much greater degree of freedom by controlling blood sugar levels up to 24 hours at a time. Novo Nordisk posted US$ 1.8 billion in sales that year, and its "modern insulin" segment posted a 49 percent gain in 2006. The prognosis from Novo Nordisk is that Levemir sales will reach US$ 522 million in the USA by 2011. Competitors Sanofi Aventis with their long-acting insulin product Lantus expect sales of a total US$ 1.5 billion in the same period.
Despite these advances in treatment, the WHO keeps pointing out the crucial role of prevention. After all, the worldwide surge in diabetes, now at pandemic proportions, can be traced directly to rapid in-creases in obesity and physical inactivity. These trends are reflected most alarmingly in the previously rare reports of type 2 diabetes in children, which in some countries now account for almost half of newly diagnosed cases.
Read more about the inventors: Svend Havelund, John Broberg Halstrom, Ib Jonassen, Asser Sloth Andersen, Jan Markussen (Denmark)