Arnold Bloom

ISLET-CELL ANTIBODIES IN DIABETES MELLITUS

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.

Prolonged Coma in Simmonds's Disease

The significance of the fact that this patient had been treated with oral chlorpromazine, 25 mg. three times a day, for the fourteen months previous to his admission was not appreciated at the time, and consequently he was given a normal anaesthetic for his age and weight, with the somewhat anaesthetically distressing results. The post-operation tachycardia and absence of vomiting are a well-known feature of chlorpromazine premedication. This case suggests that care should be exercised in giving normal doses of anaesthetic drugs to patients taking chlorpromazine.

EFFECT OF SHORT AND LONG TERM CHLORPROPAMIDE TREATMENT ON INSULIN RELEASE AND BLOOD-GLUCOSE

Abstract 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.

IS GLUCAGON IMPORTANT IN STABLE INSULIN-DEPENDENT DIABETICS?

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 homoeostasis or ketone-body metabolism in ambulant insulin-dependent diabetic patients.

Glucose Content of Serous Pleural Effusions

Bacteriological confirmation of the tuberculous origin of non-purulent pleural effusions may be difficult to obtain by direct culture, while the result of a guineapig inoculation will not be available for several weeks. Where negative results are obtained, radiography and sputum examination may not be helpful, and a search was therefore made for other diagnostic criteria. Experience gained from glucose estimations of the cerebrospinal fluid in tuberculous meningitis directed attention to the possible diagnostic value of the glucose content of pleural fluid.

Assessment of the need for continued oral therapy in diabetics.

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.

Controlled Trial of Methandienone in Treatment of Diabetic Retinopathy

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.

Further experience with oral therapy in diabetes.

Tolbutamide has proved to be a successful hypoglycaemic agent in many diabetic patients. It is well tolerated and safe, and it does not lead to severe hypoglycaemic symptoms. Nevertheless, it suffers from two disadvantages. First, its effective action is short-lived (Stowers et al., 1958), and so it has to be given twice daily. Second, it is successful mainly in patients with mild diabetes with onset at maturity (Marble, 1958). Hence there is a need for compounds which are effective in a wider range of diabetics and with a more prolonged action. Short-term trials of a new oral hypoglycaemic agent can determine in what type of diabetic the agent is successful, its length of action, and whether it is well tolerated. Long-term trials are necessary before the possibility of toxic effects can be eliminated with confidence. Carbutamide proved to be a well-tolerated and effective oral hypoglycaemic agent, but it had been in use for over a year in Germany

Phenformin in Insulin-Dependent Diabetics

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.

Oral Treatment of Diabetes

evident from Table V, where the results are given for those infants with maternal antibody levels of 16 or less-levels which produced little or no interference with antibody response. Although the numbers are small, it appears that, in the case of types 1 and 3, the older the infant the better the response to vaccination, although in the older groups there was still a high proportion who did not respond, especially to type 1. With type 2, however, the age of the infant had no effect on the response, because in all groups all the infants except one responded well to this type.