One may say this about a number of things, but to an Endocrinologist, the discovery of insulin is perhaps the most remarkable of all. Insulin is a hormone that is produced in the body by the pancreas, a small organ that lies just behind the stomach. It allows the body to appropriately utilise glucose obtained from food. The absence of insulin is not compatible with life. Thus, prior to the advent of insulin, diabetes mellitus was invariably a death sentence. Since then, the use of insulin has saved countless lives and will continue to do so in the future. However, despite the revolutionary way it has changed medical practice, the molecule continues to have image problems. Several misconceptions exist, as well as a certain fear with regards to its use. These often hinder the administration of insulin, lead to suboptimal medical management, and increase the risk of morbidity and mortality in patients.
In previous issues of Diabetic Living, several myths relating to insulin have been proved groundless. However, to understand insulin further, one must start at the beginning. Diabetes mellitus was first recognised by the ancient Egyptians in approximately 1500 BC. The term diabetes, thought to have first been used by the Greek physician Aretaeus, is derived from Greek word diabetes (to siphon). In the 6th century BC, an Indian healer named Sushruta further described the disease and coined the term Madhumeha or sweet urine, as these patients literally produced sweet urine. Ancient Indian physicians used to confirm the diagnosis by determining if ants were attracted to a patient’s urine. Due to this observation, in 1675, Thomas Willis modified the name by adding on the Latin word mellitus, meaning sweet. Unfortunately, right through till the turn of the 20th century, having diabetes was considered fatal. Modalities such as exercise and various forms of diet were tried, but were unsuccessful.
In 1919, Dr. Frederick Madison Allen from the Rockefeller Institute published an approximately 600 page manuscript titled Total Dietary Regulation in the Treatment of Diabetes. This endeavor placed patients on a severe calorie/carbohydrate restriction, in what was referred to as a ‘starvation diet.’ Unfortunately, this only prolonged the lives of sufferers by months. In 1921, Frederick Banting and Charles Best showed that they could reverse diabetes in dogs by giving them an extract from the pancreas of healthy dogs. Subsequently, with the help of James Collip and John Macleod, this extract was further purified. In 1922, Leonard Thompson, a young boy of 14, became the first person to receive and be successfully treated with insulin.
The Advent of Insulin
In 1923, following this success, pharmaceutical companies started making insulin commercially available. Thousands who had previously faced an almost certain demise, began to survive for extended periods of time. However, things were still not perfect. For almost 60 years following the discovery of insulin, patients had to take a hormone that was purified from animals. The human body’s natural reaction to foreign protein led to adverse reactions like skin rashes. In 1978, Genentech produced the first synthetically manufactured insulin, which provided a long awaited alternative to animal insulin. Since then, the production and refinement of insulin has been at the forefront of medical science.
Currently, several different types are available, each with a specific use and duration of action. This gives patients tremendous flexibility in adapting insulin to fit their lifestyle. Gone are the days when patients were dependent on vials, glass syringes and large bore needles. Insulin pens have greatly facilitated the portability of insulin, allowing users to take multiple injections a day, if required. All that patients have to do is press the pen against the skin and click. Dose delivered! Furthermore, the needles that come with it are as small as 4mm in length, minimising if not completely eliminating the sensation of a prick. Insulin pumps have further revolutionised the delivery of insulin. These prevent the need for multiple injections and provide a steady infusion of insulin 24 hours a day. The rate of infusion can be adjusted to suit a person’s diet and activity schedule, and the insertion site needs to be changed only every three days. Oral insulin is currently being developed, and inhaled insulin is once again on the horizon.
Having said all this, some pivotal questions still remain. Why is there so much focus on insulin? What does insulin actually do? Do we really need insulin? These are some of the issues that are often raised during a clinic visit. As mentioned above, insulin is instrumental in controlling blood sugar levels. However, not every patient with diabetes needs insulin. A very simple explanation of the gross patho-physiology underlying the development of diabetes lies in this analogy. Let us imagine the body as a well and the pancreas as a small pump that fills the well with water (insulin). There are certain individuals that are born with a defective pump, and hence do not produce enough insulin, i.e. are not able to pump enough water into the well. These individuals, or patients with type 1 diabetes mellitus, need to be given insulin to survive. In patients with type 2 diabetes mellitus, the size of the well or the weight of a person changes with the passage of time. Filling a larger well with water takes more effort, and gradually the small pump starts to burn out and not function as well as it used to. Here, oral medications are like spare parts that either increase the body’s sensitivity to the insulin being produced, or try to squeeze out more insulin from the pump (pancreas). Eventually, there comes a time when the pump is just not able to produce enough insulin to meet the body’s requirements, despite help from oral medications. This necessitates the need for insulin to be given to correct this deficiency.
Undoubtedly, insulin has a major role in the treatment of diabetes mellitus. Until a permanent cure for this ailment is discovered, it will remain essential for survival in those with type 1 diabetes mellitus. When used in a timely and appropriate fashion, it can also be of great benefit to those with type 2 diabetes mellitus. Yet, several misconceptions exist about the molecule and its use. Understandably, questions, concerns and fears may arise during the initiation of insulin. It is imperative that physicians/educators work closely with patients to alleviate these and clear any doubts that may exist. Only then will this transition process be as smooth and as painless as possible.
By : Dr. Amit Bhargava