Dr. S.M.Sadikot.
Hon. Endocrinologist,
Jaslok Hospital and Research Centre,
Mumbai 400026

Hypoglycemia is considered by many to be the most common emergency associated with the management of diabetes. Some call it an acute "complication" whilst others deem it to be a "side-effect" of the treatment. The latter feel that as the aim in the treatment of diabetes is to bring the blood glucose levels to as near normal as possible, hypoglycemia should be considered as a greater than required effect of the treatment! Whether it is a "complication" or a "side- effect", no one disputes the fact that hypoglycemia is very much an emergency that should be, if not avoided completely, at least recognized at the earliest so that vigorous steps can be taken to prevent any damage to the patient.

Today, when "tight" control seems to be the mantra of glucose management, there are many who feel that it is not really possible to achieve tight control without the patient experiencing some episodes of hypoglycemia, especially those of a relatively mild nature.

Without entering into a debate about this, it is well accepted by everyone that the patient should not have severe, prolonged or even numerous mild episodes of hypoglycemia. Whilst it is fairly widely recognized that a severe attack can lead to significant morbidity and even death, it is much less widely known that even recurrent so-called "mild" attacks of hypoglycemia can lead to complications which are similar to those that have been termed as long term diabetic complications. Ironically, these are the very same problems we would like to avoid by offering the patient a good and tight control!

I would like to discuss the traditional signs and symptoms of hypoglycemia with a special emphasis on the very early and subtle manifestations. Later we will see what are the measures which one can take faced with the likelihood of experiencing hypoglycemia.

Let us first discuss the classical signs and symptoms of hypoglycemia. These fall into two main categories: the sympathoadrenal (those caused by the increased activity of the autonomic nervous system) and the neuroglucopenic (caused by a decrease in the activity of the brain due to a decreased supply of glucose).

The adrenergic signs and symptoms are weakness, sweating, increased heart rate, palpitations, trembling especially of the fingers, feeling of nervousness, irritability, a tingling or a funny sort of feeling in the mouth and fingers, hunger and sometimes nausea and vomiting. It is very important to realise that these signs and symptoms of "sympathoadrenal" activity occur whenever the blood glucose levels are falling very RAPIDLY!

In fact, the faster the rate of fall of the blood glucose levels, the greater the manifestations of this over activity. In other words, these signs and symptoms may not necessarily reflect the actual levels of blood glucose but are significantly dependent on the rate of its fall. Thus, they may occur even if the blood glucose levels are low, normal or even higher than normal! I should be admitted that there are some experts who do not completely agree with this and feel that these signs and symptoms would only occur with a low blood glucose. Most of the others feel that whilst, often these manifestations are accompanied with a low blood glucose, they are dependent on the rate of fall of the blood glucose rather than its level per se. In any case, what one has to remember is that whilst these signs and symptoms should warn of a possible hypoglycemic reaction and corrective measures should be taken, it should also keep in mind that they may be due to treatment itself which is causing the blood glucose levels to fall too rapidly although they may not as yet be in the low range.

In my experience, this is usually seen if the patient is using heavy doses of regular insulin or in some normal or underweight patients who are initially on heavy doses of oral hypoglycemic agents. In such circumstances, a decrease in the amount of insulin and/or oral agents may alleviate the signs and symptoms completely!

In contrast, the signs and symptoms associated with "neuroglucopenia" are only seen when the blood glucose levels are truly in the hypoglycemic range. They do not seem to have any relationship with the rate of fall of the blood glucose levels. The manifestations are caused by a lower supply to the brain of glucose than its requirements. The signs and symptoms include headaches, low temperatures, visual disturbances, mental dullness, confusion, forgetfulness, convulsions and coma.

In the classical manifestation of hypoglycemia, both, the "sympathoadrenal" and the "neuroglucopenic" signs and symptoms are seen, although some may not show the former manifestations. Once again, it is important to realise this, due to the fact that many patients are under the impression that unless they exhibit the signs and symptoms associated with sympathoadrenal overactivity, they cannot be undergoing a hypoglycemia episode! Therefore, problems such as headaches, confusion, forgetfulness, sight disturbances, convulsions etc. are not diagnosed correctly. I have seen patients who have undergone intense and expensive investigations, made to wear spectacles, had their nasal sinuses operated, given psychiatric treatment or even shunned off as being senile when the root cause of their problems was simply hypoglycemia! All this expense, stress and mental agony could have been averted if the blood glucose had been estimated! I am not trying to imply that all these problems cannot occur in a patient with diabetes, they can. But, as I will stress again later, in any patient who presents with medical problems, hypoglycemia should always be near the top of the differential list.

Having made this point, let us consider some of the common situations where a patient may not exhibit the signs and symptoms of "sympathoadrenal" overactivity.

As mentioned earlier, if the blood glucose levels fall very slowly, these manifestations may be absent even if the actual level of blood glucose is in the hypoglycemic range. Many diabetics have neuropathy and its presence may not allow the sympathoadrenal signs and symptoms to manifest. Others who have high blood pressure are put on quite high doses of drugs like beta blockers. These drugs can also lead to a blocking of the signs and symptoms that we traditionally associate with hypoglycemia.

Quite a few patients will exhibit signs and symptoms when they are truly hypoglycemic which do not come into the categories of the "classical" manifestation of hypoglycemia as described above. If patients become excessively quiet, show a lack of interest, is unnaturally good or conversely becomes fretful, highly irritable and prone to throw "temper tantrums", hypoglycemia should be ruled out. This is especially true in children with Type 1 diabetes. Similarly, when adult patients become morose, ambitionless, are. depressed without adequate reason, complain of feeling weak and faint, become very irritable and are apt to lose their tempers without any real or worthwhile provocation especially if in the past, they have been relatively calm persons, or behave abnormally, 1qw blood glucose levels should be ruled out as a first step.

In other words when any person with diabetes shows behaviour which is not in keeping with his "usual" self, one should consider hypoglycemia as the cause of the problem. Very often, the patients themselves are completely unaware of this change in attitude and behaviour and therefore, it is imperative for the family and fellow workers to be aware of these aspects so that they can draw attention to this and corrective measures could be taken.

In my experience, it is usually the family that is able to see the change in behaviour of the patient. To give an example, one wife of a patient complained to me that her husband was very irritable and was very rough with his children who previously used to be the "apple" of his eyes. He always used to complain that the children were noisy and that he had no peace and would beat them up on the slightest provocation. It had reached such a stage that the young children had been sent off to their grandparents house and there was a distinct possibility of the marriage breaking up! Hypoglycemia was the cause of this behaviour and a decrease in the dose of oral agents that he was taking solved the problem completely and the family is back happily together.

One of the most difficult diagnosis to make is that of "subclinical" hypoglycemia. One example that we could take is that of hypoglycemia occurring at night during sleep. This may not be severe enough to cause coma, or even cause the patient to sweat so that he complains that when he gets up, his clothes and even the bed sheet is drenched. In my experience, asking the patient whether he experiences night sweats, has early morning headaches or has vivid and bizarre dreams and nightmares often offers subtle clues to the fact that the patient may be undergoing hypoglycemic episodes in his sleep. At the same time, let me make it clear that the level of blood glucose estimated in the morning at the fasting state, even if this higher than normal, is not proof that one may not be having hypoglycemia at night. This fasting blood glucose levels may be manifestation of the Somogy Effect, where hypoglycemia at night, during sleep, can cause a reactive (or rebound) hyperglycemia.

One point of great clinical importance is that most patients have their own characteristic pattern of showing hypoglycemia reactions and this pattern often remains constant for the patient, It is imperative that patients, their family and the treating doctor be thoroughly familiar with this characteristic pattern so that any hypoglycemia can be recognized at the earliest and treatment given before there is any serious and long lasting damage.

I would like to discuss a couple of situations that may lead one into thinking that we are not dealing with hypoglycemia, in spite of the fact the patient is truly hypoglycemic and also exhibits all the typical signs and symptoms of hypoglycemia These situations should be known as they needlessly delay the diagnosis and treatment of hypoglycemia and may thus lead to serious consequences. Often, the patient or the doctor will examine the urine for sugar when the patient complains of hypoglycemia manifestation. One may be surprised to see that the urine does contain a moderate or even high concentration of sugars. This, leads to the wrong conclusion that the patient does not have hypoglycemic as many feel that when the sugars are present in the urine, it shows a high blood glucose level. Conversely, some are under the false impression that in hypoglycemia, the urine should not show any sugar. What we forget is that what one examines, may have been in the bladder for quite a while and that, during this period, the patient may have had a high blood glucose level with a consequent leak of the glucose in the urine. Therefore, the urine that has been in the bladder will not correlate to the situation at the time that the manifestation of hypoglycemia occur! If one were to completely empty the bladder and then after a few minutes pass some more urine, one may find it to be devoid of any sugars! Also there are some diabetics who have a low renal threshold for glucose. In other words, they leak glucose into the urine even when the blood glucose levels may be as normal or even lower than normal. Again in these patients, there may be sugar in the urine during hypoglycemia. In these patients, if the threshold is sufficiently low, even the second void specimen of the urine may show the presence of sugar! Therefore, the presence of sugar in the urine should not mislead us to rule out the possibility of hypoglycemia. If there is any doubt about the matter, an immediate blood glucose estimation may give the correct clue to the diagnosis.

Unfortunately, sometimes, even the estimation of blood glucose levels may obscure the true story. Many patients live near a laboratory and may go there quite easily and hurriedly, if required. When these patients estimate the blood glucose levels around the time they had manifestations of hypoglycemia, especially the signs and symptoms of "sympathoadrenal" overactivity, some are surprised to find the blood glucose levels to be normal or even much higher than normal! Thus, they are confused whether they are really experiencing hypoglycemia or not. This, in spite of the fact, that they were truly hypoglycemic. Here again, it must be rea1ised that when a patient undergoes a hypoglycemic reaction, especially if it is associated with quite a rapid fall in the levels of the blood glucose, the body tries to fight the hypoglycemia by using counter measures like over activity of the sympatho-adrenal system and other hormones like cortisol and growth hormone. When fighting hypoglycemia by these counter measures, there is no way that the body can finely regulate the counter response such that the blood glucose levels reach only to a normal value. Often and especially if the rate of fall in the blood glucose is very rapid there is an overshoot of the counter measures and this may push the blood glucose to a level much higher than normal! Thus when this blood glucose level is estimated and the results are found to be high the patient wrongly feels that he does not have hypoglycemia. This, in spite of the fact, that the patient manifests all the signs and symptoms of hypoglycemia and was truly hypoglycemic! This again leads to a crucial delay in the diagnosis and consequent treatment of hypoglycemia with all its attendant problems. Scarily if, in view of the higher than normal blood glucose levels that are seen, the patient increases the doses of insulin and/or oral agents, it is quite possible that he may go into a worse episode of hypoglycemia or even be in coma.

In view of the above mentioned situations, I feel that it would be better to go by clinical judgement rather than depend blindly on the laboratory results which may put us on a false trail. It is always worthwhile to treat any such manifestations as hypoglycemia, take the necessary treatment for the same and also decrease the dose of insulin and/or oral agents and see whether the problems are still present. It is quite possible that were the manifestations due to hypoglycemia, these would stop with a decrease in the dosage.

Many patients are worried that if the problems were not due to low blood glucose level, the decrease in the dosage would further increase the blood glucose levels I do not think that this is a very important matter as one would be just as capable of normalising these raised blood glucose levels as one would the original high levels. But at least the patient would be protected from the damage the hypoglycemia may and does have the potential to cause.

The management of hypoglycemia in a diabetic patient is fairly simple when the diagnosis is done at an early stage and this should be explained to all the patients as well as to a member of the family. All that one may have to do is to have a meal, snack or even a beverage with some easily absorbed carbohydrates. In an emergency, one could also take some simple sugars or a drink with simple sugars. In later stages, especially if the patient has become stuporous and the teeth are tightly clenched, the mouth may not open. Some doctors advocate that under such circumstances one could try and push some thick form of sugar solution or honey between the teeth and the cheeks, in the hope that some of this may be absorbed from the inner lining of the cheek and this may allow the patient to become slightly more conscious so that simple sugars can then be taken by mouth. I would like to warn against this. It is possible that the solution may be aspirated and lead to serious respiratory problems.

It is very important that after patients have taken simple sugars and become better, they must take a meal having complex carbohydrates. This will be slowly absorbed and help in keeping the blood glucose levels even after the rapid effect of the simple sugars has worn off, especially when the hypoglycemia causing agent is still present in the body. This is an extremely important point and unless this is followed, it is quite possible that the patient may recover from one episode of hypoglycemia and later relapse again, possibly in a more severe form and at a time when help may not be forthcoming in time! This is specially true when the hypoglycemia is caused by long acting insulin preparations and by oral agents, especially chlorpropamide. Although, most of the books and even the literature that comes along with these tablets mention that the drug is effective for 36 hours, it is my clinical experience that when a patient goes into hypoglycemia caused by this drug, the effect may be prolonged up to 5 days. The patient keeps going into repeated attacks of quite severe hypoglycemia and I feel that if the hypoglycemia is caused by such an agent and especially if it has been of a serious nature, the patient should be admitted to hospital as many of such patients even need glucose drips for 4-5 day's in order to recover and prevent any further attack of hypoglycemia.

I do not accept the statement that a diabetic cannot be well controlled without exposing him to the hazards of hypoglycemia, even though these be of a mild nature. At the same time, it is also possible that many patients will sometime or the other experience some episodes of hypoglycemia. With the modern management of diabetes, these episodes of hypoglycemia should be rare and mild. With an understanding of the various ways by which hypoglycemia may manifest, it would be possible to diagnose hypoglycemia at an early stage. The mild attacks of hypoglycemia, especially when diagnosed in the incipient stages can be quite easily managed using some of the measures detailed above, which not only would help in the early treatment of hypoglycemia but would also help in preventing further episodes of hypoglycemia, due to the same cause, from taking place.

But what does one do when faced with a very severe hypoglycemia reaction, especially one in which the patient becomes comatose? Whilst such situations should not theoretically arise with the modern management, unforeseen problems may arise and it would be worthwhile for the family members of the patient to be aware of what needs to be done in these circumstances. Of course, one could always shift the patient to a hospital. But this takes time, and every minute counts when dealing with a severe hypoglycemic reaction if one is to prevent any major and irreversible damage. It is obvious that the patient requires glucose, but the difficulty is in administering it to an unconscious patient. The obvious thing to do would be to give glucose intravenously, but this is not feasible for most families. Even if one manages to get a doctor in a hurry, it is an unfortunate fact that many of us do not carry vials of glucose in our emergency bags! Therefore, it may be worthwhile for patients, especially those who are "brittle" and prone to frequent and severe episodes of hypoglycemia to keep a few vials of glucose and the materials for injection so that a doctor could use them in an emergency.

A better option for such patients is to keep a vial of glucagons with them. As this is to be injected intramuscularly, anyone can easily be taught to give this injection. This is especially true as most of the families where a member is on insulin, have other members who know how to give the injection. I also feel that glucagons should be on the emergency medicine list of every doctor. 0.5 mg -1mg given intramuscularly is often sufficient to raise the blood glucose levels in comatose patients by about 20-25mg%. This enables many of the comatose patients to regain slight consciousness so that they are able to take sugars orally. Although the dose in adults is 1mg., it is better to initially inject 0.5 mg and see the result. If there is no improvement, the other 0.5 mg can then be injected. The reason for this is that in some patients glucagons can cause nausea and vomiting and this would not allow the patient when he does regain some consciousness to take any sweets orally.

If in spite of these measures, if the patient does not recover, a shift to a hospital is essential. The patient would require, besides glucose, intravenous steroids and mannitol. I feel that the doctor who may see the patient at home before transfer to the hospital should be in such circumstances inject 100mg. of hydrocortisone, both intravenously as well as through the muscular route. This can be a life saving measure. In fact, I feel that even if the patient seems to recover completely from what seems to have been a very severe attack of hypoglycemia, it may be better to hospitalise the patient for any further management and observation, especially if the hypoglycemia has been caused by a long acting insulin or by chlorpropamide.

One should also insist that all diabetes patients carry a card with them which clearly states that they have diabetes along with the contact phone number. This would prevent the very common occurrence of bystanders not giving any help as they feel that the patient is drunk.