Hypoglycemia

Hypoglycaemia is the major hazard of insulin treatment, and problems have increased in the drive to achieve “tight control”. Patients may experience the symptoms of hypoglycemia when the blood concentration is less than 3.0 mmol/l. However, individual susceptibility varies considerably and it is interesting that some patients whose control has been persistently very poor for long periods appear to experience hypoglycaemic symptoms at levels a little above this. The risks of hazard from hypoglycemia are small in most patients, but because they exist at all, patients taking insulin are barred from certain occupations such as driving trains or buses. All patients taking insulin whose diabetes is reasonably well controlled will experience hypoglycaemia at some stage. At its mildest, it is no more than a slight inconvenience, but at its severest, when unconsciousness can occur, it is both a hazard and an embarrassment. Furthermore, manipulative patients can use hypoglycemia to threaten family and friends. This sword of Damocles is ever present once insulin treatment has started, and the need to use measures to avoid it requires constant, indeed lifelong, vigilance. Hypoglycemia occurs infrequently in patients taking oral hypoglycaemics.

Hypoglycaemia (“hypo” “insulin reaction”)

• This is when the blood sugar goes too low in diabetics taking insulin
• Symptoms are sweating, shaking, tingling round the mouth, hazy eyesight or seeing double, slow thinking, in children naughtiness
• Causes are late meal, too little carbohydrate, extra exercise, too much insulin.
• Cure is to take carboydrate — preferably three dextrosol tablets, glucose, sugar (two large lumps), barley sugar, Lucozade followed by a small snack
• Symptoms will soon wear off
• If in doubt about an attack, take sugar
• Always carry some form of SUGAR with you

Symptoms

Most patients experience the early warning symptoms of hypoglycemia and can take sugar before more serious symptoms develop. These warning symptoms are well known and are described in the box. Tremulousness and sweating are by far the commonest symptoms, while circumoral paraesthesiae is the most specific. Many patients have highly individual symptoms of hypoglycemia which range from quite inexplicable sensations to peripheral paraesthesiae. In three patients carpal tunnel compression resulted in tingling fingers when they were hypoglycemic, representing their sole warning. Neuroglyopenic symptoms and diminished cognitive function follow if corrective action is not taken, with progressive confusion and eventually unconsciousness and occasionally convulsions. There is a prolonged debate as to whether recurrent hypoglycaemia causes long-term intellectual decline; the evidence in general is unconvincing although major and recurrent episodes in childhood may have an adverse effect in this regard.

Patients who become unconscious from hypoglycemia need urgent treatment. Brain damage and death do not normally occur because the blood glucose concentration tends to increase spontaneously as the effect of the insulin wears off and the normal counter-regulatory responses become effective. Many diabetics, especially children, need reassurance that they will not die in their sleep. Nevertheless, a very small number of otherwise unexplained deaths at night have been reported in Type 1 diabetic patients (described as the “dead in bed” syndrome) and no precise cause has ever been established. Deaths from prolonged hypoglycaemia are most likely to occur after insulin overdoses, as a result either of a suicide or murder attempt, but even in these circumstances most patients recover.

Symptoms of hypoglycaemia
• Early warning	Shaking, trembling Sweating Pins and needles in lips and tongue Hunger Palpitations Headache (occasionally)
Neuroglycopenia
• Mild	Double vision Difficulty in concentrating Slurring of speech
• More advanced	Confusion Change of behaviour Truculence Naughtiness in children
• Unconsciousness	Restlessness with sweating Epileptic fits, especially in children Hemiplegia, especially in older people (but rare)

Observation of a hypoglycemic attack

“When she is having a hypo she gives the impression of being drunk. The change in her behaviour is sudden and very noticeable. She slurs her words and appears drowsy. There is lots and lots of yawning. If she is still in the state of which she can walk, she will bump in to things and knock things over and be generally clumsy. She will hardly be aware of where she is or who she is talking to. She rambles”

Diminished awareness of hypoglycaemia

This is the problem which all insulin treated patients dread, and at some stage it affects up to one quarter of Type 1 diabetic patients. It occurs when patients do not experience the early warning symptoms and directly develop diminished cognitive function which prevents them from taking the required preventive action. In this situation, help is required from a third party. This commonly occurs in the home when friends and relations observe the person to be slow-witted with a vacant expression and perspiring face. They may be taciturn, truculent or even obstructive, sometimes refusing to take sugar when advised, although many learn to accept this advice. This state of cognitive impairment can persist for some considerable time, long enough for abnormal behaviour to be noticed during driving, even for several miles; shoppers in the High Street may be unaware that they are shoplifting. If corrective action is not taken, the more serious state of unconsciousness already described can occur.

Night-time hypoglycemia is very common, usually occurring between 3 and 6 am. The blood glucose concentration often falls below the hypoglycaemic threshold; levels as low as 1.0 mmol/l are not rare, and are known to cause electroencephalogram abnormalities even in the absence of symptoms. Many people become very restless when hypoglycaemic; this is recognised most frequently by the spouse who takes the necessary remedial action. Profound sweating is common, sometimes necessitating a change of nightclothes or bedclothes and may be the only manifestation that hypoglycemia has occurred. Convulsions are not rare, and some patients wake in the morning with a bitten tongue as the only indication that this may have occured.

Recurrent hypoglycaemia is the principal underlying cause leading to diminished awareness of hypoglycemia, with dangerous impairment of cognitive function its chief manifestation. It is therefore most likely to occur in those who are most tightly controlled, and was manifest in the famous Diabetes Control and Complications Trial (DCCT) in which severe hypoglycaemia occurred three times more often in the tightly controlled group of patients. This cause outweighs all others, although the use of (3 adrenergic blockers has the same effect in a small number of patients. Autonomic neuropathy is not normally the cause of diminished warning, and the contentious role of human insulin in this regard has led some patients to change back to animal insulins, though scientific evidence of harm is still lacking. Diminished warning also increases with lengthening duration of diabetes.

Why does recurrent hypoglycaemia beget loss of warning? The answer probably lies in the readjustment of the threshold of sensitivity of a glucose sensor in the hypothalamic region of the central nervous system. This alters the hierarchy of responses to hypoglycaemia. Thus, the hypoglycaemic symptoms and counter regulatory responses, instead of occurring at a blood glucose just above 3.0 mmol/l, develop at a lower level, rather less than 2.0 mmol/l. Because in either case the loss of cognitive function occurs around 2.8 mmol/l it is clear that, in cases of diminished hypoglycaemic awareness reduced cognitive function develops before hypoglycemic warning symptoms.

Avoiding hypoglycaemia can restore proper warning symptoms. Patients should try to avoid blood glucose levels <4.0 mmol.

Recent research has also shown that by eliminating recurrent hypoglycemia it is possible to restore the normal sequence of events when blood glucose falls, thus also restoring adequate warning. It is therefore necessary to eliminate as far as possible all hypoglycemic episodes, even those occurring quietly at night. This can often be achieved simply by reducing the insulin dose, ensuring adequate carbohydrate intake and to some extent relaxing overall diabetic control in the interest of safety. It is much more difficult, yet possible, to eliminate hypoglycemia and retain optimal control of diabetes. The acquired skill of the diabetes team and the co-operation of patients is needed if this is to be done, and the time and resources needed are considerable. The introduction of programmes such as blood glucose awareness training (BGAT), in which patients are taught how to recognise the most subtle symptoms of early hypoglycaemia, can be very effective in reducing serious hypoglycaemia and thus helping to restore adequate warning.

A questionnaire which helps physicians to assess whether a patient has diminished awareness of hypoglycemia is shown in site.

Causes of hypoglycemia

In every patient taking insulin the blood glucose concentration shows peaks and troughs, which can be most clearly shown by home measurements of blood glucose. Since the lowest blood glucose concentrations occur at different times in each patient, it is a great advantage if individual patients know when their own troughs are likely to occur. The commonest times are before lunch and during the night. Some patients in their constant fear of developing diabetic complications drive their blood glucose levels ever lower with disastrous consequences in terms of hypoglycaemia.

Severe physical activity, such as swimming very long distances, is a powerful stimulus of hypoglycemia, and as much as 40 to 50 g additional carbohydrate may be needed to prevent it. Hypoglycaemia in these situations is sometimes delayed for several hours. Several well-known sportsmen and women with diabetes show considerable ingenuity and perseverance in the way in which they cope with their diabetes during international competitions, by individual attention to food and insulin intake, carefully timed blood glucose monitoring, and ready availability of sugary fluids such as Lucozade at exactly the right moment.

Events likely to provoke hypoglycaemic attacks

• Insufficient carbohydrate in meals
• Delayed meals
• Increased physical activity
• Errors of insulin dosage
• Erratic insulin absorption from areas of fat hypertrophy at injection sites

Hypoglycemia is particularly likely to occur shortly after stabilisation of new patients, as their insulin requirements may decline considerably; their insulin dose should therefore always be reduced before they leave hospital.

Hypoglycaemia is also troublesome when insulin requirements insidiously decrease during the evolution of such conditions as Addison’s disease, hypopituitarism, and malabsorption syndromes.

Items containing 10 g of carbohydrate
• Milk	200 ml (1/3 pint)
• Lucozade	60 ml (4 tablespoons)
• Ribena	15 ml (1 tablespoon)
• Coca Cola	90 ml
• Sugar	2 teaspoons
• Sugar lumps (small)	3
• Dextrosol tablets	3

Treatment and prevention of hypoglycaemia

Much of the skill required to manage insulin treated diabetic patients is therefore devoted to achieving adequate control of diabetes, yet avoiding hypoglycemia. There are quite straightforward measures which many patients neglect: they must therefore at all times carry a supply of glucose both on their person and in their cars, and take 10 to 20 g at the first warning symptoms, preferably followed by a carbohydrate snack. The late RD Lawrence always demanded that his patients should demonstrate that they were carrying their sugar supply with them. This can take the form of sugar lumps, sweets (non-diabetic), sugar gel or dextrose tablets.

They should take ample carbohydrate at times when blood glucose troughs occur, notably mid-morning and bedtime, and they must take appropriate amounts of additional carbohydrate before and during vigorous exercise. Careful blood glucose monitoring plays a crucial part in avoiding hypoglycaemic episodes, and helps to restore warning of hypoglycemia. Patients should try to avoid blood glucose levels below 4.0 mmol/l. Appropriate insulin regimens that need to be devised for individual patients are described in chapters 5 and 6.

Glucagon

Glucagon is a hormone produced by the A-cells of the pancreatic islets. It raises the blood glucose by mobilising the glycogen stores in the liver (and therefore will not work after prolonged starvation). It is given in a 1 mg dose by injection most conveniently intramuscularly. It can also be used subcutaneously or intravenously and is effective in five to 10 minutes. It is of great value for bystanders of severely hypoglycaemic patients who are unable to take oral glucose, and can be injected by family members, nurses or doctors. It is valuable in relieving stress in a home where a diabetic patient, often a child, is prone to recurrent disabling attacks of hypoglycemia.

Unconsciousness

In cases where the patient has lapsed into severe unconsciousness, treatment in hospital is urgently needed. The unconscious patient should be placed in the recovery position, and the airway maintained. Blood should be taken for blood glucose analysis and the sample should be kept in case the patient fails to respond to treatment since the possibility always exists that the coma has another cause. Intravenous glucose is given using 50 ml of 20% glucose solution. The more concentrated 50% solution is highly irritant and should no longer be used. The response is usually immediate but if not, a further dose should be given after five to 10 minutes followed by an infusion of 10% glucose. Once consciousness is restored and a history can be taken, the patient should be fed with longer acting carbohydrate to prevent recurrence. If recovery does not occur rapidly, blood glucose measurement should be repeated and another cause for the coma must be sought. If hypoglycaemia has been profound, cerebral oedema can occur and may require treatment with dexamethasone or mannitol. After recovery appropriate adjustment must be made to the diabetic treatment in order to avoid further episodes, and the patient should be carefully reviewed in the diabetic clinic.

Dr Charles Fletcher’s account of hypoglycaemia

My main problem has always been hypoglycemia. At first I was nearly always aware of it by day and woke at night, because of the adrenaline response. But, particularly in the past 20 years, it gradually became more difficult. I may now feel normal and do ordinary tasks quite easily with blood sugar as low as 2.5 mmol/1 (45 mg/100ml). Sometimes diplopia, dysphasia, weariness, or inability to think may lead me to do a blood sugar. But I often become too muddled to know what is wrong, and I have had to thank my wife, my children, and many generations of housemen, registrars, and secretaries for spotting these low levels on many occasions. Before I retired 50% glucose was always available with syringe in a drawer in my desk. I became quite used to a quiet registrar’s voice in outpatients (and elsewhere) saying, “I think, sir, a little extravenous glucose might help”. Lucozade has been invaluable. I always have it available in the car, in the office, and at home. It is acceptably free from sugariness, it saves me chewing and choking on dry glucose tablets, and it is rapidly absorbed. My wife finds it much easier to get me to drink this than to take any other form of sugar when I am severely hypoglycaemic and refuse to acknowledge it. I have made it a rule, which I now keep, even when semi-comatose, that if my wife — or anyone else — tells me to take sugar I do so however sure I may be that I’m not hypoglycaemic. They have only been wrong on rare occasions. I am very sensitive to exercise, but for some reason I find it difficult always to suck prophylactic sweets on country walks or when digging or mowing in the garden.

Hypoglycaemia due to oral hypoglycaemics

This may occur during treatment with sulphonylureas and similar agents (but not with metformin) especially in some confused elderly patients who either inadvertently take additional tablets or omit their meals. It is treated in the same way as described above. These patients usually require admission to hospital for continuous glucose infusion to avoid relapse into hypoglycaemia, which often occurs until the drug has been cleared from the circulation.

Conclusions

Any serious hypoglycaemic episodes can to some extent be regarded as a failure of the doctor, the patient or the treatment regimen itself. It should provoke a serious inquiry to establish the cause and to discover if it is likely to recur. The opportunity for the necessary education should be taken, and patients should be encouraged to carry a diabetic identification card. Finally, the professional attending the patient, whether doctor or nurse, has a duty to inform people who have had an episode of severe hypoglycaemia comprising diminished cognitive function resulting from diminished awareness of hypoglycaemia to stop driving and inform the Driver and Vehicle Licensing Agency. They should also avoid any other potentially dangerous activity. The endeavour to avoid hypoglycemia needs to be maintained, and patients need considerable support to this end at almost every diabetic consultation throughout life.

The story of Mrs B-J continued: hypoglycaemia

When I was 12 I was sent to The Old Palace School in Cray don. Never having done any gymnastics, I was surprised at what was expected of me at the new school. Rope climbing, parallel bars, and marching up and down the long hall where kings had been entertained by archbishops, I was soon very hypo and staggering about like a drunk. This disrupted the session so much that finally I was banned from gym and all other sports. My fellow diabetic, Barbara, had also been banned, but it did not worry me too much. But it was a bitter blow when I was told I would not be allowed to take part in the school pageant “in case I was ill”! My mother went up to see Sister and assured her I would have plenty of sugar etc., but to no avail. Gentle nuns can be very obstinate and quite hardhearted at times.