Low-dose insulin treatment of hyperosmolar diabetic coma.

The effect of low-dose hourly i.m. injections of insulin has been studied in the treatment of 17 episodes of hyperosmolar non-ketoacidotic diabetic coma compared with 26 episode of hyperosmolar ketoacidosis occurring in patients over 40 years of age. The fall in blood sugar was satisfactory in the majority of episodes of both types of coma and there was no evidence that patients with hyperosmolar non-ketoacidotic coma were more sensitive to insulin. The excess mortality in the non-ketotic group (47%) compared with the ketoacidotic group (16%) was not due to uncontrolled diabetes.

Plasma arginine vasopressin in diabetic ketoacidosis.

Plasma Arginine Vasopressin (AVP) was measured serially in 10 patients during the first 24 hours of treatment of diabetic ketoacidosis. AVP was elevated in all cases initially, ranging from 4.0--122.0 pmol/l, the basal level in healthy hydrated subjects being 1.57 +/- 0.59 pmol/l (+/- 1 SD). The levels fell progressively during the course of treatment. While there was no evidence that the massive increases in AVP noted in this study were associated with water overload it remains to be determined whether the high levels observed have any significant metabolic or haemodynamic role in this disorder.

Very pure porcine insulin in clinical practice.

In a one-year follow-up study the insulin dose in diabetic patients using very pure porcine insulin was compared with that in patients using conventional preparations. The dose of insulin used to obtain diabetic control was reduced by 7% in 108 patients treated solely with very pure porcine insulin from the start of insulin treatment when compared with 108 matched patients who had received conventional insulins. In 117 patients whose treatment had been changed from conventional bovine or bovine-porcine insulin to very pure porcine insulin the dose was reduced by 9%. A further 511 patients receiving conventional insulins were examined for local cutaneous or subcutaneous abnormalities at insulin injection sites. Lipoatrophy was found in 49 of these patients (10%), but not in patients using very pure porcine insulin. The results confirm that very pure porcine insulin reduces the insulin dose needed to maintain diabetic control and may resolve or prevent local reactions such as lipoatrophy. Long-term advantages in reduced antigenicity to insulin and contaminating peptides remain to be established.

Diabetic pregnancy: management of diabetes on the day of delivery.

An insulin regimen for management of the insulin dependent diabetic on the day of delivery is described. Pregnant diabetics were fasted on the day of delivery and infused with 10g glucose per hour throughout labour and after delivery until normal eating was resumed. In the morning a fixed dose of intermediate acting insulin (NPH 24 units) was administered subcutaneously at 8:00 A.M. This dose was found suitable for women whose insulin requirements during pregnancy ranged from 60 to 250 units/day. The regimen worked satisfactorily both under close study conditions and also when used routinely and was equally applicable to the diabetic scheduled for induction or for elective Caesarian section. It was associated with an 8% incidence of foetal distress amongst women who were induced. Neonatal hypoglycaemia affected 19% of all infants, the incidence rising from less than 10% amongst infants of women with the best control to 41% amongst infants of women with the worst control. No cases of maternal hypoglycaemia during or after delivery were recorded.

Neonatal morbidity among infants of diabetic mothers.

While the modern approach to management of diabetic pregnancy has reduced the perinatal mortality significantly, the neonatal morbidity remains high. This study has investigated factors which may account for the persisting high neonatal morbidity when birth trauma has been virtually eliminated and the incidence of respiratory distress syndrome (RDS) considerably reduced. Major congenital malformations emerge not only as the leading cause of perinatal losses but also as an important cause of morbidity. Delivery before 37 weeks increased the incidence of RDS and hypocalcemia, and it is suggested that, when strict metabolic control is used and with the help of facilities to monitor the fetus closely in the last weeks of pregnancy, the number of infants delivered at this early date can be further reduced. The present study also indicates that normoglycemia should also be encouraged on the day of delivery as maternal hyperglycemia at this stage increases the incidence of neonatal hypoglycemia. Jaundice, which very commonly affects newborn infants of diabetic mothers, is influenced by the use of oxytocin for vaginal delivery and by infant overweight (greater than 90th percentile) at birth, factors which are not beyond control. Finally, route of delivery per se may not be important in relation to neonatal morbidity.

Diabetes mellitus and coeliac disease: a clinical study.

Fourteen adults in whom diabetes mellitus and coeliac disease coexist, are described. In no patient was coeliac disease diagnosed (biopsy proven) before the age of 28 years. Diabetes was recognized before coeliac disease in all except one. Diabetic control was very unstable and hypoglycaemia particularly troublesome before treatment with a gluten free diet. Following gluten restriction, insulin requirement increased in six patients, and diabetic control became more stable. Diarrhoea due to coeliac disease in a patient with coexisting diabetes, may be mistakenly diagnosed as 'diabetic diarrhoea'. However, certain clinical and laboratory features should arouse suspicion that the diarrhoea is not of diabetic origin. These included a history of gastrointestinal symptoms preceding the diagnosis of diabetes, the occurrence of repeated hypoglycaemia, absence of neuropathy, anaemia, low serum folate, low serum albumin and a malabsorption pattern on small bowel radiography. A definitive diagnosis of coeliac disease can be made only jejunal biopsy. The opportunity to diagnose coeliac disease in adult diabetics will usually fall to the diabetologist and wider use of jejunal biopsy in diabetics with chronic or recurrent diarrhoea is suggested.

Menstruation and control of diabetes.

Seventy per cent of the patients aged 45 years or under and suffering from diabetic ketoacidosis who were seen in one diabetic clinic over five years were women. The association of menstruation with ketoacidosis was assessed over two and a half years, and it was found that menstruation was associated with ketoacidosis more often than would be expected by chance (P less than 0-01). Two hundred women were interviewed and 76 observed that menstruation changed their diabetic control. Fifty-three found that control deteriorated and hyperglycaemia occurred, while 23 found that control improved and hypoglycaemia was a common problem. Menstruation appears to be an important factor in influencing control of diabetes. The mechanism of the changes observed has not yet been determined, but it seems to be a subject worthy of further investigation.

Changes in systolic time intervals during treatment of diabetes mellitus.

The cardiovascular response to the control of diabetes by sulphonylurea drugs has been investigated using systolic time intervals in a group of 19 diabetics. Before treatment a significantly greater heart rate and shortening of QS2 interval and left ventricular ejection time index were encountered among the more hyperglycaemic diabetic patients requiring drug therapy while all diabetics had a reduction of pre-ejection period index. There was a gradual return of resting heart rate and systolic time intervals to control values along with the fall in plasma sugar concentration during treatment. A likely explanation of the findings is that uncontrolled diabetics, particularly those more severely affected, are subjected to an increased adrenergic stimulus to the cardiovascular system which disappears with therapy. There is no evidence of positive inotropic action of sulphonylurea drugs in this study.

Congenital malformations in infants of diabetic mothers.

In a series of 701 infants born to diabetic women between 1950 and 1974 ,57(8-1 percent) had congential malformations which is a rate three to four timeshigher than in the normal populations of Birmingham.. In 26 cases(3-8 per cent) the malformations were fatal and accounted for 26 per cent of the perinatal mortality in the series. Central nervous system, cardiovascular and skeletal abnormalities were equally common and there was a high incidence of anencephalus, spina bifida, transposition of the great vessels and sacral dysgenesis...

Studies in whole body potassium and whole body nitrogen in newly diagnosed diabetics.

Serial measurements of whole body potassium and whole body nitrogen were carried out in 18 newly diagnosed diabetcs. Initial measurements were made before treatment of diabetes was commenced, and further measurements were carried out following the start of treatment. Six patients required insulin and the remainder were treated either with diet alone (four cases) or with diet and oral hypoglycaemic agents. Significant increases in whole body potassium and whole body nitrogen were noted following control of diabetes.Thesees. These changes were most marked in the patients treated with insulin. The techniques used for measurement of body potassium and nitrogen offer considerable advantages over conventional metabolic balance studies and the results indicate that the losses of potassium and nitrogen during period of poor diabetic control are much greater than that has been realized.

Comparative study of different insulin regimens in management of diabetic ketoacidosis.

36 patients in severe diabetic ketoacidosis were studied prospectively. All patients were treated with small doses of insulin, the first 18 by the intramuscular route and the remainder by continuous intravenous infusion. These patients were compared with 25 ketoacidotic patients who were treated with large intravenous boluses of insulin. With the intramuscular regimen there was a slower fall of blood-sugar than with intravenous insulin administered either in boluses or as a continuous infusion. The acidosis took longer to correct when small doses of insulin were used. In practice a long time interval between correction of the hyperglycaemia and correction of the acidosis may be a problem when the continuous infusion of insulin is used. Potassium requirements during treatment were identical (30-40 mmol/l fluid infused) and independent of the insulin regimen. However, small doses of insulin led to a poor retention of potassium. In the management of diabetic ketoacidosis the mode of administration of insulin is of limited significance, and small doses, although effective in most cases, are not clearly superior to conventional treatment with large doses.

Insulin antibodies and the control of diabetes.

Seventy-two insulin-treated diabetic patients were classified on the basis of a clinical evaluation of their control of diabetes. There were 39 stable patients, 23 unstable patients and 10 patients of intermediate degree of control. Four insulin resistant patients were also studied. Serum insulin antibodies were measured in each patient and the concept of insulin buffering by its antibody was developed. Most unstable patients had low concentrations of insulin antibody. Twenty-four of the 39 stable patients had a significant concentration of insulin antibody and 15 patients had low levels of antibody. The insulin resistant patients had hugh levels of antibody. All unstable patients had low antibody buffering and all insulin resistant patients had high antibody buffering. Although many stable patients had buffering antibodies others lacking antibody required a low insulin dose and their stability of diabetic control was attributed to residual pancreatic function.