Search

We report on the growth and doping of InAs by atomic layer epitaxy (ALE). The InAs layers were grown using ALE cycles in a metal organic chemical vapor deposition reactor, and Si doping of the films was studied for different SiH4 flow sequences. When SiH4 was added to trimethylindium during the group-III step, the silicon concentration in the film was above 5 × 1019 cm−3. When SiH4 was added to tertiarybutylarsine during the group-V step, much lower incorporation of Si was observed. Conformal Si doped InAs layers were selectively grown by ALE on In0.47Ga0.53As patterned layers made on silicon substrates, demonstrating the suitability of the growth method for III-V device technology on silicon.

The term ‘diabetes” includes a heterogeneous group of disorders characterised by an elevated blood glucose. The maintenance of blood glucose at normal levels depends on the integrity of the islet cells, their capacity to produce insulin in response to appropriate stimuli, the fate of insulin in the liver and at the periphery and the interplay between insulin and other hormones. Diabetes can result if the islet cells are destroyed, for example, by viruses or antigens, or are functionally imperfect and respond poorly to stimuli. These and other defects may be determined by heredity, by environmental factors or by disorders of other endocrine systems.

A self-administered questionnaire, designed to detect symptoms and side effects of treatment in diabetes, was completed by 437 patients (94% response rate). Patients were subdivided into treatment groups, and symptoms assessed in relation to therapy, age, duration of diabetes and blood sugar. Fifty per cent of patients were receiving oral hypoglycaemic agents alone, 30% were on insulin and 20% were on diet alone. Patients on phenformin complained significantly more of stomach pains, diarrhoea, headache and cramps in the legs; patients on glibenclamide of dry mouth and nocturia, and patients on chlorpropamide of slow walking pace and burning in the limbs. In patients on glibenclamide or phenformin weakness of the limbs, unrelated to blood sugar or age, was increased. One third of patients on insulin suffered attacks of sweating and confusion. A total complaint rate for each therapeutic group was calculated. Highest complaint rates occurred in patients on phenformin and on glibenclamide, whilst chlorpropamide compared favourably with diet alone. Patients under 59 yr of age tolerated oral hypoglycaemic agents less well than insulin or diet alone; in elderly diabetics there was a progressive rise in complaints on insulin but a highly significant decline in symptoms on tablets.

Forty-four diabetic patients maintained on insulin entered a doubleblind crossover trial. They were given clofibrate 2 g daily for 6 weeks, either before or after a period of 6 weeks on placebo.Clofibrate did not cause any material change in insulin requirements and there was no change in body weight. Drug tolerance was good.The mean blood glucose was significantly lowered while taking clofibrate. Plasma fibrinogen and pre-beta-lipoprotein concentrations were also significantly decreased following clofibrate therapy.

1. In its present form Dextrostix does not provide a reliable measure of blood glucose. 2. When modified and simplified it proved of great value in the management of diabetes in certain clinical situations.

Hypoglycaemic agents were replaced by placebos in diabetic patients attending a hospital clinic. Of 62 patients observed, 43 (69%) relapsed within six months but blood sugar control remained unchanged in 19 (31%) during the period of observation.

Forty-one diabetic patients on insulin were given 100mg. of phenformin daily for six weeks, either before or after a period of six weeks of inert capsules, in a double-blind cross-over trial. Eleven patients while on phenformin noticed hypoglycaemic effects and reduced their insulin on average by almost 20% without resultant rise in blood sugar levels. Twenty-eight patients felt no untoward effects and maintained their usual insulin dose. Phenformin led to improved control of the diabetes, with a significant decrease in blood sugar levels and a significant reduction in the variability of the weekly blood sugar readings. There was no increased ketosis, no change in cholesterol, and no significant loss of weight.

The effect of chlorpropamide on β-cell activity was studied in newly treated diabetics and in those who had previously received prolonged therapy. Chlorpropamide did not restore the impaired ability of the β-cell to produce insulin in response to an intensive stimulus of glucose, tolbutamide, and glucagon. In newly treated diabetics, there was a transient increase in insulin output. However, in patients previously treated with chlorpropamide, although reintroduction of the drug led to a fall in blood-sugar, there was no increased insulin output. These findings make it likely that the main hypoglycaemic action of chlorpropamide is extra-pancreatic and that the increased output of insulin is transitory and only contributory in newly treated cases.

In severe diabetes, there is no substitution for insulin. However, since 1955 tablets have been available for the treatment of mild diabetes developing in middle age. These tablets do not contain insulin and are not substitutes for insulin. They bring down the level of sugar in the blood to normal in mild diabetics and are consequently referred to as oral hypoglycaemic agents. This is regarded as a better term than anti-diabetic tablets since it does not imply that these tablets overcome all the features of diabetes. They merely reduce the raised blood sugar to normal.

As has been described in a previous chapter, a large percentage of patients with diabetes can now be restored to normal blood sugars by watching their diet and taking appropriate tablets, without recourse to insulin. Nevertheless, there remains a type of diabetes which cannot be controlled without insulin. This is true of almost all cases of diabetes developing in children and in young adults. However, it is not only young diabetics who must be controlled with insulin and it is a mistake to assume that when diabetes develops in an older age it can necessarily be managed without insulin. Indeed, sometimes very elderly patients develop severe diabetes which does not respond to tablets and which cannot be controlled without insulin. In the main, patients who are underweight are unlikely to be controlled without insulin as are patients who show considerable acetone as well as sugar in the urine. The presence of acetone suggests a more serious derangement of metabolism and this is unlikely to be corrected by tablet treatment. Indeed, considerable amounts of acetone in the urine is perhaps the single most important indication for the need for insulin.

One hundred and seventy-six patients who were newly referred to two diabetic clinics completed an initial questionnaire and a second questionnaire 1 yr later. Over the 1-yr period the average 2-h postprandial blood sugar was reduced from 13.8 to 8.8 mmol/L. The questionnaire included 33 questions on symptoms, and four symptoms improved by more than 10%: increased thirst (reduced by 29%), dry mouth (reduced by 24%), pruritus (17%), and weakness in the limbs (10%). No symptom was increased by more than 7%. The changes in five symptoms were significantly related to the changes in blood sugar observed, the improvement in symptoms being associated with reductions in blood sugar. These results are contrasted with newly referred hypertensive patients in whom marked improvements in symptoms were not observed and an increased frequency of certain symptoms was observed owing to drug side effects.

The diagnosis of diabetes depends on the level of sugar in the blood. This definition immediately poses difficulties because there is considerable variation in blood sugar levels in normal people. For example, the blood sugar rises normally after a meal and falls again when we are fasting. Usually, in the fasting state on rising in the morning, the amount of sugar in the blood is about 80 mg/100 ml, (4mmol/l) but after breakfast this may rise to 120mg/100ml (7mmol/l). Normally, the blood sugar seldom exceeds 160mg/ 100 ml (9 mmol/1) even after eating a heavy meal containing a lot of sugar. In diabetes, the blood sugar is elevated above normal and usually exceeds 200ml/100ml (11 mmol/1). However, there is no precise point at which it is possible to say that diabetes is present since occasionally blood sugars may temporarily rise above normal levels. Some help in the diagnosis may be given by testing the urine.

Islet-cell antibodies (I.C.A.) were found in 38% (319/829) of insulin-dependent diabetic patients, in 5% (6/112) of insulin-independent diabetics, and in 1·7% (3/177) of non-diabetic subjects. In the insulin-dependent group I.C.A. were found in 85% of patients immediately after the onset of symptoms and they became less common as the duration of disease increased. I.C.A. were equally common in both sexes and the decline in their prevalence was independent of age. The antibodies were directed against cytoplasmic components of islet cells but not against insulin itself. The appearance of I.C.A. probably follows cell damage occurring before the onset of symptoms. By contrast, thyroid and gastric autoantibodies were more common in older patients and females. There was no correlation between the presence of these antibodies and I.C.A. in patients with either diabetes of recent onset or longstanding disease.

The exact moment of onset of diabetes can never be clearly defined and indeed there is no clear dividing line between normality and diabetes. As has been mentioned, the ability to store away excess sugar is gradually lost with increasing age so that if a definition of diabetes acceptable in younger people is applied to the older generation, we reach the absurd conclusion that the majority of people over 70 have diabetes. Since the inability to store away excess glucose may be a gradual process, symptoms may be equally insidious. Indeed, in middle age diabetes is frequently diagnosed as a result of a routine examination of the urine which reveals the presence of sugar. In many such cases, even when the diagnosis of diabetes is confirmed by glucose tolerance tests, the patient will not admit to any abnormal symptoms even on direct questioning. In children the situation is quite different. Here diabetes seems to come on much more quickly and symptoms may occur with increasing intensity. Since children seldom complain about their health, it often happens that a child is on the way to coma before the parents observe anything amiss.

The diet or meal pattern recommended for someone developing diabetes is an individual matter and will depend on many factors. Previous eating habits cannot be turned upside down, and consideration must be paid to established ethnic and family customs, as well as personal likes and dislikes. Young people need more to eat than older ones, those involved in heavy manual work need more food than those in a sedentary occupation and some people have heartier appetites than others. The overweight, middle-aged person who develops diabetes must reduce weight by dietary restriction until excess weight is lost and the sugar in the blood restored to normal. For diabetics needing injections of insulin the dietary requirements are different. Not only must the diet be adequate in amount, the meal pattern must be a regular one and spaced throughout the day. Nevertheless, despite all these individual differences, certain principles of eating must be observed for all those with diabetes if their future health is to be safeguarded.

Diabetes is uncommon in childhood and very unusual indeed in babies. It occurs equally in boys and girls and the commonest age of onset is about 12 years old.

Perhaps the one thought which most worries diabetic patients is the fear of hypoglycaemic reactions and the danger of losing consciousness. In fact, actual loss of consciousness is unusual in diabetics taking insulin and very exceptional indeed in patients taking tablets; but it is essential for every diabetic taking insulin to be aware of the early symptoms of hypoglycaemia and to take necessary action in good time.

The role of glucagon has been evaluated in the everyday regulation of carbohydrate and lipid metabolism in insulin-dependent diabetic patients. Plasma concentrations of glucagon, growth hormone, cortisol, glucose, and free fatty acids and blood concentrations of glycerol, 3-hydroxybutyrate, acetoacetate, alanine, pyruvate, and lactate were measured in 38 fasting diabetic subjects deprived of their usual morning dose of insulin. The measurements were repeated in 25 of these patients after a further 3 hours of insulin deprivation and in 6 patients again at 6 hours. There was no correlation between the initial fasting levels of plasma-glucagon and those of the other biochemical measurements including glucose and ketone bodies. Furthermore, no correlation was found between changes in these measurements and in plasma-glucagon over a period of 3 or 6 hours. These findings suggest that glucagon is unlikely to play a role of primary importance in blood-glucose homœostasis or ketone-body metabolism in ambulant insulin-dependent diabetic patients.

The word mild in this context means that the blood sugar levels are not very much elevated above normal and so the condition does not give rise to troublesome symptoms. Indeed, as often as not there are no symptoms at all and the diagnosis is made by the chance finding of sugar in the urine. This may happen because the patient has been examined for a life insurance policy or because he has seen his family doctor and examination included a routine urine test. Mild diabetes usually comes on in middle age and is often diagnosed by chance in this sort of way. It must be stated, however, that although the term mild is true as far as symptoms are concerned, this form of diabetes can lead to considerable damage to the health of the patient unless it is adequately treated.

Sulphormethoxine is a sulphonamide with a prolonged action, which makes possible the treatment of some varieties of acute urinary tract infection with a single dose of 2 g. In a controlled trial on ambulant patients it was as effective as a seven-day course of ampicillin given in a dose of 500 mg. eight-hourly. The cure rate was 88% with both substances. Side-effects occurred in 3.8% of patients treated with sulphormethoxine and in 16.1% of those who received ampicillin. Sulphormethoxine is not recommended for acute pyelo nephritis. Dr. Gr?neberg was in receipt of a grant from the North-west Metropolitan Regional Board. Dr. I. Lennox-Smith, of Roche Products Ltd., kindly arranged for a supply of sulphormethoxine.