11th January 1922 is a red letter day in the history of diabetes. Culminating a summer of hard work, epoch making experiments, many failures and finally, what could be "success", Frederick Banting and Charles Best were convinced that they had isolated insulin. Now it had to be proved that what they had isolated would work in humans.

Leonard Thomson, was a 14 year old boy with insulin dependent diabetes. On 11th January 1922, the first injection of insulin, as prepared by the two doctors, was given to Leonard. Subsequently, other patients too were injected with insulin by Banting and Best. It would be worth while to quote the results in their own words. Writing in the Canadian Medical Association Journal, Banting summarised his findings as follows:

"Following the production of what appears to be a concentrated internal secretion of the pancreas and the demonstration of its physiological activity in animals, and under careful control, its relatively low toxicity, we are presenting a preliminary report on the pharmacological activity of this extract in human diabetes mellitus. Clinical observation at this juncture would appear to justify the following conclusions: (1) Blood sugar can be markedly reduced even to normal values. (2) Glycosuria can be abolished. (3) The ace- tone bodies can be made to disappear from the urine. (4) The respiratory quotient shows evidence of increased utilisation of carbohydrates. (5) A definite improvement is observed in the general condition of these patients and in addition the patient themselves report a subjective sense of well-being and increased vigor for a period following the administration of these preparations".

Euphoria accompanied the availability of insulin. It was hoped that we would be able to prevent the acute and also the chronic long-term complications of diabetes. To a certain extent, the hopes have proved true. There is no doubt that insulin therapy has allowed a number of people with diabetes to live a much longer and better life than it would otherwise have been possible.

In 1982, a banquet was held in New York attended largely by insulin dependent diabetics. The Chief Guest, one of the first individuals who had received insulin from the hands of Banting himself put matters in the right perspective, " If today, this hall resounds to the vibrant voices of living beings, and not to the ghoulish wailings of our ghosts, it is entirely due to the great courage and spirit of two radicals who had the confidence, some would call it obstinacy, to believe in themselves, even in the face of adversity. If the world does make progress, it is due to such free thinkers, rather than those who would rather follow the straight, safe and well trodden path."

At the same time, we must accept that the initial euphoria that "diabetes had been defeated" was, and is, misplaced. Whilst it has been possible to prevent, or adequately manage acute complications of diabetes like ketoacidosis, we have failed to prevent or treat some of the long term complications of diabetes.

Whilst it would be naïve to feel that the longterm complications of diabetes are so simple that they would have a single etiology, there is enough evidence to show that good control of diabetes can prevent, to a large extent, and definitely alleviate most of these dreaded complications affecting the eye, kidneys, nerves etc. Then why is that in spite of having insulin in our therapeutic armamentarium, we are unable to offer optimal control and thereby prevent these very complications? Could it be that we have been unable to optimise the use of insulin thus far?

The most important stumbling block to the optimal use of insulin seems to be the inablity to define and understand the precise role that insulin therapy should play in our management of diabetes. Very often, patients who should preferably be on insulin are treated with massive doses of oral agents without effective control of the blood glucose levels, whilst many obese Type 2 patients, who have a fair amount of endogenous insulin, and should be managed with diet and exercise are administered excessive doses of insulin in an attempt to bring about control. I think that it is this "abuse" of insulin with all its attendant problems that prevents us from offering our diabetics the best possible "use" of insulin therapy and as a consequence, optimal management of their diabetes.

So which patients should receive insulin therapy?

Patients Who Should Receive Insulin Therapy 1 ) It is obvious that insulin therapy is mandatory for all Type 1 patients;

2) Any diabetic with significant chronic complications like coronary artery disease, cerebrovascular disease, peripheral artery disease, neuropathy, retinopathy, nephropathy etc. should receive insulin;

3) Any diabetic with an acute problem like severe infections, injuries etc., should be given insulin;

4) All diabetics with tuberculosis should always be given insulin;

5) Most diabetics undergoing surgery may need to be stabilised on insulin;

6) Pregnant diabetics, if not tightly controlled with diet and exercise should be given insulin to ensure tight control;

7) Any patient, even if well controlled on oral agents, who shows even the slightest evidence that may contraindicate the use of oral agents. For example, a liver disorder should entail stopping of the tablet and the patient should be shifted over to insulin;

8) All underweight patients and those with malnutrition related diabetes should be given a high calorie diabetic diet and covered with insulin;

9) Patients with INSULIN-REQUIRING diabetes, even though they are not prone to ketosis, should be identified and their management supplemented with insulin to get the best possible control;

I really feel that once a decision is made that a person would do better with insulin therapy, it becomes essential for the doctor to be able to convince the patient that insulin injections are the best for the patient. No compromise should be entertained about administering it. It is true that many of our patients have a great aversion to taking insulin and overcoming this resistance is quite a difficult problem. Unfortunately, many doctors give in to this resistance. Although, they may offer many excuses for this, I am quite skeptical of most of these. I feel that the real reason is that they are afraid of losing the patient to some other doctor who will give the patient oral tablets. I think that this attitude is indefensible. If the patient needs insulin, then there is no compromise in so far as the doctor is concerned. Having treated quite a few patients with diabetes, a substantial number of whom are on insulin, I feel that the major contributing factor to the initial patient resistance is the totally false and anecdotal concepts that they have about the problems and dangers associated with insulin therapy.

Simple explainations to clear these misconceptions, accompanied with a certain amount of firmness and occasionally a threat about the potential loss of eye, limb and/or life, is often sufficient to overcome the initial patient resistance, Later, once patients are well stabilised on insulin, they feel so much better that they often opt to continue the insulin therapy. A few patients benefit by being hospitalised,. especially in a diabetic unit. Seeing other patients receive, or take their own, injections of insulin, somehow seems to make the concept of taking insulin injections much more acceptable. In these diabetic units, they also see patients with foot problems which may have needed amputation, patients with vision loss etc., and this too helps in their resolve to take insulin. I have known many "adamant" patients accept insulin injections after a short period of hospitalisation.

At the same time, it is essential to add a word of caution.

It is widely felt that high insulin levels in the blood may be an important factor in causing associated problems such as obesity, hypertension, lipid disorders and atherosclerosis (Syndrome X). Thus, one should guard against a misplaced enthusiasm to use insulin in all Type 2 patients unless they fall into one of the categories listed above.

As we have discussed in the section dealing with oral agents, the hyperglycemia in many Type 2 patients is mainly due to peripheral resistance to the action of insulin. In such patients the optimal treatment would be to use drugs insulin " sensitisers" such as glitazones and/or metformin. Even in those who also have a decreased secretion of insulin from their beta cells, it may be worth while to see if the use of small doses of insulin "secretagogues" would optimize the control.

It is only when a rational use of oral agents fails to provide the desired levels of control that one would add insulin to the therapy under normal circumstances.

There should be NO misplaced enthusiasm to use insulin in all diabetic patients. Of course, the pendulum should not completely swing the other way. Those who need insulin MUST be given it!

After deciding that a patient will need to take insulin, the next step is to decide which insulin one will use.

Such a great plethora of insulins are available for clinical use that there is often some confusion about which insulin to use. In this context, it is interesting to note that even 10 years back more than 43 different varieties of insulin were available in the U.S.A. and that these were made by just 3 companies!

But the picture much more clear, if one realizes that when choosing the insulin, there are two major areas. The first, which in my opinion is relatively minor, is the species of insulin one will use. The more crucial area is the "time of activity" characteristics of the insulin.

Species of Insulin It is really unfortunate that there has been so much controversy generated regarding the species of insulin to be used. I think that this is a relatively minor matter, and the time, money and effort spent in generating this controversy could easily have been put to better use.

The insulins available for routine clinical use are the beef, porcine and human insulins. Basically this means that the beef or Bovine insulins are got from beef pancreas, the porcine insulin is got from pig pancreas whilst the "human" insulin is manufactured through genetic engineering.

Today, all insulins available are of the pure variety and the contamination is not an issue.
Beef insulins differ from human insulin in three amino acids, whilst porcine insulin differs from human insulin in only one amino acid. Thus, porcine amino acids are less immunogenic than beef insulins. At the same time, it must be mentioned that this does not significantly affect the efficacy of the bovine or porcine insulins in most patients.
Human insulins are replacing the other insulins in most developed countries, but its cost is the inhibiting factor to its widespread acceptability in most developing countries.

I personally feel that the decision about the species of insulin to be used should be a matter best left to the patients and their doctors. At the same time, many experts feel that that there are certain circumstances where it may be better to use the "human" variety of insulins.

Patients who should preferably use human insulins are: a) All patients who are on beef or porcine insulins and manifest resistance due to the presence of antibodies;

b) Patients requiring intermittent therapy, i.e. patients with gestational diabetes, those undergoing major surgery, patients with acute infections, etc., who otherwise may be controlled on diet, with or with out OHA's, should use human insulins.

c) Patients who require very large doses of beef or porcine insulins (>80 units/day), may benefit with change over to human insulins.