Islets of Hope information for persons with diabetes

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Article disclaimer

Edited for content by Lahle Wolfe, this article is largely a reprint, courtesy Wikipedia.com

Sources for this article
Wikipedia.com
The Wiley Insulin History Page
Discovery of Insulin
History of Diabetes


A brief biography of Dr. F. G. Banting

Courtesy of Discovery of Insulin, a website dedicated to preserving the birthplace of Dr. Frederick Grant Banting. Please visit their site for thorough information about Dr. F. G. Banting or to support their cause.

Dr F G Banting

Frederick Grant Banting completed his medical studies at the University of Toronto and established a surgical practise in London, Ontario, supplementing his income as a medical demonstrator at the University of Western Ontario. In London he conceived a technique which might permit isolation of the anti-diabetic component of the pancreas. He returned to the University of Toronto in 1921 to conduct experiments on the pancreas at the labs of Dr. J.J.R. MacLeod. By the time the summer had ended, he and Charles Best had isolated insulin. Dr. J.B. Collip developed the process by which insulin was able to be refined and processed in sufficient amounts for clinical trials. Fame came quickly to the soft-spoken Banting who won the Nobel Prize for Medicine because of his discovery. Many honours followed, including knighthood, and Banting continued to work on further research and coordinated the National Wartime Medical Research effort. His efforts were cut short by a fatal crash in Newfoundland in 1941.


 type 2 diabetes source book  Drum/Zierenberg
The Diabetes Type 2 Sourcebook:  
This book provides all the information readers need to know about living with Type 2 diabetes, including self-management, the most recent findings on nutrition and exercise, the emotional and financial issues that accompany the disease, and the newest testing methods, treatments, and medications. Also includes an up-to-date listing of helpful organizations and other resources. Terry Zierenberg, R.N., C.D.E., is the program coordinator for the  Diabetes Care Center at Encino-Tarzana  Regional  Medical Center in Los Angeles, CA


Links to information about insulin

injecting insulin, how to
insulin delivery devices
insulin pens, general information
insulin pens, step-by-step guide how to use
insulin pump resource & information sites
insulin pump therapy
insulin pumps, types of pumps
insulin reactions, shock, allergies, sensitivity, resistance
insulin, types of insulin
intensive (flexible) therapy
injecting insulin
insulin pumpers (tips)
mixing, storing & preparing insulin
(tips)
conventional therapy
insulin storage (chart)


psyching out diabetes  Richard R. Rubin, Ph.D., C.D.E.
Psyching Out Diabetes:  
This book examines the psychological obstacles of diagnosis such as panic, fear, anger, shame, and guilt and how to put them into perspective. Through proper maintenance, diet, and education, this book is tailor-made for the diabetic or anyone with a diabetic in their life who wants to overcome the negative emotions associated with this disease and learn the coping skills necessary to integrate diabetes into their daily life.  Dr. Rubin is a faculty member of the John's Hopkins Medical School.

 

Diabetes Medical Library                       main "Diabetes Information" page
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A brief history of diabetes and insulin


insulin crystals
Magnified insulin crystals

Mini Site Index
What is Diabetes?
Brief History of Diabetes
History of Insulin
History of  Types of Insulin

What is Diabetes?

Diabetes mellitus is a medical disorder characterized by varying or persistent hyperglycemia (elevated blood sugar levels), especially after eating. All types of diabetes mellitus share similar symptoms and complications at advanced stages. Hyperglycemia itself can lead to dehydration and ketoacidosis. Longer-term complications include cardiovascular disease (doubled risk), chronic renal failure (it is the main cause for dialysis), retinal damage which can lead to blindness, nerve damage which can lead to erectile dysfunction (impotence), gangrene with risk of amputation of toes, feet, and even legs. The more serious complications are more common in people who have a difficult time controlling their blood sugars with medications (glycemic control).

The most important forms of diabetes are due to decreased or the complete absence of the production of insulin (type 1 diabetes), or decreased sensitivity of body tissues to insulin (type 2 diabetes, the more common form). The former requires insulin injections for survival, while the latter is generally managed with diet, weight reduction and exercise in about 20% of cases,the majority require these strategies plus oral medication and insulin is used if the tablets are ineffective.

Patient understanding and participation is vital as blood glucose levels change continuously. Treatments which return the blood sugar to normal levels can reduce or prevent development of the complications of diabetes. Other health problems that accelerate the damaging effects of diabetes are smoking, elevated cholesterol levels, obesity, high blood pressure, and lack of regular exercise.

   


Brief History of Diabetes

Although diabetes has been recognized since antiquity, and treatments were known since the Middle Ages, the elucidation of the pathogenesis of diabetes occurred mainly in the 20th century.

Until 1921, when insulin was first discovered and made clinically available, a clinical diagnosis of what we now call type 1 diabetes was an invariable death sentence, more or less quickly. Non-progressing type 2 diabetics almost certainly often went undiagnosed then; many still do.

The discovery of the role of the pancreas in diabetes is generally credited to Joseph Von Mering and Oskar Minkowski, two European researchers who, in 1889, found that when they completely removed the pancreas of dogs, the dogs developed all the signs and symptoms of diabetes and died shortly afterward. In 1910, Sir Edward Albert Sharpey-Schafer of Edinburgh in Scotland suggested diabetics were deficient in a single chemical that was normally produced by the pancreas - he proposed calling this substance insulin.

The endocrine role of the pancreas in metabolism, and indeed the existence of insulin, was not fully clarified until 1921, when Sir Frederick Grant Banting and Charles Herbert Best repeated the work of Von Mering and Minkowski but went a step further and managed to show that they could reverse the induced diabetes in dogs by giving them an extract from the pancreatic islets of Langerhans of healthy dogs. They went on to isolate the hormone insulin from bovine pancreases at the University of Toronto in Canada.

This led to the availability of an effective treatment - insulin injections - and the first clinical patient was treated in 1922. For this, Banting et al received the Nobel Prize in Physiology or Medicine in 1923. The two researchers made the patent available and did not attempt to control commercial production. Insulin production and therapy rapidly spread around the world, largely as a result of their decision.

The distinction between what is now known as type 1 and type 2 diabetes was made by Sir Harold Percival (Harry) Himsworth in 1935; he published his findings in January 1936 in The Lancet.

Other landmark discoveries include:

  • identification of sulfonylureas in 1942
  • the radioimmunoassay for insulin, as discovered by Rosalyn Yalow and Solomon Berson (gaining Yalow the 1977 Nobel Prize in Physiology or Medicine);
  • Reaven's introduction of the metabolic syndrome in 1988
  • identification of thiazolidinediones as effective antidiabetics in the 1990s.  

   


History of Types of Insulin

Original text courtesy of http://www.caerlas.demon.co.uk/insulin.htm, with edits to suit the IOH website.  Please visit the original site for exhaustive historical information on insulin and diabetes medical devices.

Regular Insulin - The first types of insulin were quick- and short-acting ("soluble" or "regular" insulin). Other names used for this first insulin include 'R' and 'Actrapid'. The insulin was injected at least twice daily and many diabetic patients stabilized on four injections a day taken at meals and bedtime.

At the time of insulin's discovery, August Krogh of Denmark, was in the USA at the time to talk about his research work on capillaries for which he was a Nobel Prize winner. During his talks he heard about insulin and went to Toronto to learn more. Later, Krogh and H.C. Hagedorn laid the foundation of the great Danish insulin manufacturing industry when they founded the Nordisk Insulin Laboratorium in 1923. The Nordisk Insulin Company was a non-profit-making company and along with the Novo Company, was responsible for making Denmark the main insulin-producing country outside the USA. Novo Terapeutisk Laboratorium was founded two years later.

Protamine - NPH - Regular insulin was not adequately serving patient needs.  It peaked at 2-4 hours with an activity curve of under 8 hours for most patients.  A longer-acting insulin which could be injected before sleeping without such a strong peak was needed to help avoid early-night hypoglycemia.  A longer-acting insulin would also be more efficient at helping with "dawn phenomenon,"  a rise in blood glucose during that night.  While even non-diabetics also experience this effect, they are able to produce insulin to correspond with this rise in blood glucose; diabetes cannot and experience nighttime hyperglycemia.

1936 protamine zinc insulin was introduced. - it uses the protaphane or protamine polypeptide to delay and prologue the insulin activity curve. At Nordisk, Hagedorn developed Isophane insulin (Neutral Protamine Hagedorn - or NPH) in 1946 (also called Insulatard). This new insulin was a neutral insulin with prolonged action. Unlike the early protamine insulin, it could be mixed with Regular, and the activity curves of both Regular and NPH would remain identical - with a mix of Regular and Protamine, the curves would move together. For some diabetics, the 'blunting' effect of R+Protamine was a benefit, but for most, the ability to inject a mix of R+NPH, before breakfast and before dinner, was more convenient, and fitted their blood glucose curves better.

Lente Insulins - Following the introduction of NPH, a research team was gathered together at Novo with the aim of developing a similar insulin product that would be just as effective, and perhaps even better.. The research team achieved its aim. In 1953 Novo was able to present the Lente insulins - Ultralente, Lente and Semilente. For many years, a third of the world's insulin consumption was Lente family. Because the delaying agent was Zinc, to the benefits of a time-delayed insulin, there was the added benefit to patients of fewer allergic reactions. However, unlike NPH, Lente could not be mixed with R. While Lente had an activity curve similar to protamine zinc/NPH, Semilente had an action between that of R and NPH, while Ultralente had an action much longer. The three Lente insulins, plus Regular gave doctors and patients great flexibility in choosing a regime which exactly matched the diabetic's needs.

Pre-mixed Insulins - Since many doctors were prescribing regimes of fixed numbers of units of Regular and of NPH it was natural that pre-mixed insulins were marketed. The most common were a 50/50 blend of the two insulins, and a blend of 30% short acting, 70% long-acting.

Monocomponent Insulin - Impurities in insulin preparations were, in most cases, due to other pancreatic peptides which were present in tiny concentrations. In 1973, Novo produced a purer type of insulin, 'monocomponent' insulin (MC) insulin was introduced by Novo. This set a new standard in purity.

In 1982, Human Monocomponent was launched by Novo in 1982, this was the world's first insulin preparation identical to human insulin. It was pig insulin, modified by enzymes so that it was identical to human insulin.

Humalin - When Novo tried to introduce monocomponent insulin into the USA, Lilly fought back with 'human' Humulin insulins.

Before Human Monocomponent and Humulin insulins, insulin had been produced from animal sources, mainly cattle in the USA and the UK, pigs in Denmark. It is believed by some that the animal insulins provide the diabetic with better awareness of hypos, and it is certainly true that the long-acting animal insulins such as Ultralente are longer-acting than their 'human' equivalents. However, the fact that both pig and cattle differ from human insulin by one - three amino acids has lead the majority of physicians to recommend 'human' insulins. 'Animal' insulins are increasingly hard to find, particularly in the USA.

In response to Lilly, in 1987 Novo started production of human insulin, using genetically engineered yeast cells.

Lyspro - In 1989 Novo Industri A/S and Nordisk Gentofte A/S merged, and thereby moved ahead of Lilly to become the world's leading producer of insulin.

In the late 1990s Lilly developed Lispro or Lyspro (also spelled lispro, and trade named Humalog). This was approved for prescription in the UK in June 1996 (available later in the US). This insulin has a shorter activity curve than Regular. This means it can be injected closer to the meal time, even after it. Studies have shown that it does not improve control as measured by long-term indicators (HbA1c), but that it does decrease the number of hypos. Unlike R, it cannot be mixed with NPH: if this is done, the action of the H is modified so that it is closer to R (this can, of course, be of benefit to some patients). However, it can be mixed with L without any effect.

Glargine - Approved in the UK in 2002, this insulin (trade named Lantus) is being widely touted as better than other long-acting insulins because it has a very flat action curve (like Ultralente), but, unlike U, it has only a 24 action. Some people find it acts a little shorter (and some doctors don't believe that's possible!!!!). Some doctors are prescribing it, in preference to pumps, to diabetics with marked dawn effect, or other known daily basal insulin requirement variation.

Exubera - Inhaled insulin received FDA approval for sale in the U.S. for adult use.  Fall, 2005.

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 Page Updated 05/16/2006