W.P.U. Jackson

Metformin in management of pregnant insulin-independent diabetics.

SummarySixty pregnant “maturity-onset” (insulin-independent), established and gestational, diabetics were treated with Metformin in the second and third trimester after dietary treatment had failed. The incidence of Metformin failure was 53.8% in the established diabetics and 28.6% in the “gestational” diabetics. The 27 Metformin failures were transferred to other therapy, leaving for further analysis 33 patients who received Metformin up till delivery. Two neonatal deaths occurred in this group (1 congenital abnormality and 1 preterm infant) giving a perinatal mortality of 61/1000. This compares with a perinatal mortality of 103/1000 in the Metformin failure group and 105/1000 in a group of insulin-dependent diabetics treated during the same period. Apart from a high incidence of neonatal jaundice requiring phototherapy the infant morbidity in the Metformin group was low. The mothers of 3 infants with congenital abnormalities had received Metformin only during the last trimester of their pregnancy.

INSULIN RESERVE IN PATIENTS WITH CHRONIC PANCREATITIS

Abstract Sixteen patients with unequivocal evidence of chronic pancreatitis were subjected to intensive β-cell stimulation by combined intravenous injection of glucagon and tolbutamide after oral glucose. The serum-immunoreactive-insulin responses of the whole group were significantly impaired when compared with normal controls. The degree of impairment seemed to be proportional to the degree of glucose intolerance. It is postulated that the diabetic syndrome of chronic pancreatitis represents an example of acquired insulinopenia and is thus a valuable clinical model for assessing the effects of this in man.

Insulin secretion and pancreatic exocrine function in patients with chronic pancreatitis

SummaryThe relationship between insulin responses to oral glucose and pancreatic exocrine function were examined in 15 patients with chronic pancreatitis. Good correlations were found between the insulin responses and exocrine pancreatic function measured as the concentrations of pancreatic enzymes in duodenal juice after intravenous cholecystokinin-pancreazymin (CCK-PZ). There appears to be a roughly parallel loss of endocrine and exocrine function in the course of chronic pancreatitis.

Metabolic responses to oral glucose in the Kalahari Bushmen.

The plasma glucose, immunoreactive insulin, and growth hormone levels after a 50-g oral glucose load have been measured in 15 adult Bushmen subjects living in the Kalahari region of Southern Africa. Compared with 10 non-obese white controls, they showed relative glucose intolerance and significantly impaired insulin secretion. Growth hormone responses showed no significant differences between the two groups. Factors such as inadequate or unusual nutrition and stress do not appear to account completely for the abnormalities in carbohydrate metabolism observed in the Bushmen. Of interest are the clinical and hormonal similarities that seem to exist between the Bushmen and the Central African Pygmies.

Effectiveness, reproducibility, and weight-relation of screening-tests for diabetes.

Abstract Several surveys have been made in South Africa for blood-sugar levels, glycosuria, and diabetes in different racial groups. Screening methods included blood-sugar estimation after a meal and 1 and 2 hours after glucose, together with testing for glycosuria after a meal and after glucose. The 2-hour post-glucose value emerged as by far the best method, with a sensitivity of 94% and a specificity of 94% at a screening level of 120 mg. per 100 ml. Glycosuria proved to be highly specific, but its sensitivity was low. Reproducibility of blood-sugar estimations after oral glucose was assessed. The correlation between two readings in the same subjects was approximately 0·7% in all surveys. The mean level in Africans was higher on screening than in glucose-tolerance tests, while mean figures in the Indians were lower. Body-weight, corrected for height and age, did not correlate with blood-sugar level in any survey. The only correlation that could be found was with 2-hour post-glucose blood-sugar level in positive screenees who turned out to be non-diabetic. However, the prevalence of diabetes was closely connected with increasing weight among Indians, and much less so among Africans. Obesity was far more common among African women than any other group, yet they had the least diabetes.

A UNIFYING HYPOTHESIS FOR HEREDITARY AND ACQUIRED DIABETES

Abstract Data on insulin and glucagon release in response to a variety of stimuli in subjects with various degrees of glucose intolerance have indicated that differential and selective functional impairment of both alpha and beta pancreatic cells is characteristic. Subjects under consideration include those with genetic diabetes and the naturally acquired model of diabetes and prediabetes found in chronic pancreatitis. The glucoreceptor mechanism in both types of islet cell is damaged early, so that the response of both insulin and glucagon to hyperglycaemia is impaired, while the response to gut hormone (and hence to food) remains relatively intact. The early lesion in these syndromes of diabetes may thus be an acquired or inherited selective blindness of alpha and beta cells to glucose.

OVERACTIVITY OF THE ENTERO-INSULAR AXIS IN MATURITY-ONSET DIABETES

Abstract Early (0-10 minute) plasma-immuno-reactive-insulin (I.R.I.) responses to water, followed by 50 g. glucose ingestion, were measured in controls, mild maturity-onset diabetics, and patients who had undergone truncal vagotomies. One patient in each group responded to water. After glucose, the mean incremental I.R.I. response was greatest in vagotomy patients (50·3±21·3 S.E.M. μunit minute). In the diabetics (12·1±3·8 μunit minute) and controls (7·7±2·2 μunit minute) the increase in I.R.I. was much lower. The cumulative I.R.I./ glucose indices for the first 10 minutes were 0·07± 0·05, 0·89±0·41, and 1·17±0·39 in controls, diabetics, and vagotomy patients, respectively, indicating greater I.R.I. release per unit glucose stimulus in diabetics and vagotomy patients. It is therefore suggested that the vagus exerts an inhibitory influence on entero-insular pathways and that this pathway is overactive in mild maturity-onset diabetes.

Growth hormone responses to arginine infusion in patients with chronic pancreatitis: Relationship to glucose intolerance and insulinopenia

SummaryThe growth hormone (HGH) and insulin responses to intravenous arginine infusion were studied in 21 patients (13 males and 8 females) with chronic pancreatitis. Ten of these patients had glucose intolerance, 5 with fasting hyperglycaemia, while 11 patients had subnormal insulin responses to arginine. Basal HGH levels and peak responses to arginine were normal but were uninfluenced by sex, glucose intolerance, fasting hyperglycaemia or insulinopenia.