Possible dietary factors in the induction of diabetes and its inheritance in man, with studies in mice.
Explore the source record for details and available documents.
Biomedical subjects
Publications and source records attributed to J M Stowers.
Explore the source record for details and available documents.
In a study of 10 diabetic patients, each of whom was in a severely decompensated state, notable alteration of blood flow properties was observed in those six patients who were hyperosmolar. In this form of diabetic decompensation, whole blood filtration was distinctly impaired. The additional impairment was shown to be due to an accumulation of solute within the erythrocytes occurring as a consequence of hyperosmolarity. The alterations in erythrocytes were revealed by Coulter blood count abnormalities and confirmed by osmotic fragility studies. When biochemical improvement was achieved in these patients, rapid resolution of the erythrocyte abnormalities occurred. Microvascular ischaemia due to such erythrocyte alterations may be a possible explanation for the characteristic cerebral disturbances of the hyperosmolar diabetic state. Altered blood flow properties would also promote vascular thrombosis, a common terminal event in the hyperosmolar non-ketotic syndrome with associated 50 per cent mortality. An improved design of the insulin and fluid replacement therapy for patients in hyperosmolar diabetic coma might be based on the findings of these and further studies.
One hundred twelve women with impaired glucose tolerance (IGT) diagnosed by intravenous glucose tolerance test (IVGTT) after pregnancy were followed up for a period of up to 22 yr (mean 12.9 yr). About one-third have been treated with chlorpropamide and the others by diet only. At the final assessment, approximately 35% had abnormal intravenous glucose tolerance and less than 7% overt diabetes. Chlorpropamide did not prove significantly more effective than diet only. Factors associated with deterioration in glucose tolerance were age at diagnosis and follow-up and the initial fasting plasma glucose (FPG) level (greater than or equal to 5.8 mM), but obesity was less important, although it was associated with an increased rate of vascular complications. Tests for islet cell antibodies (ICA) were weakly positive in 12.5% of 72 subjects and in only 0.5% of an unselected population; they did not correlate with the final state of glucose tolerance. Only three patients developed insulin-dependent diabetes (IDDM) and did so before the ICA study was started. A comparison is made between the results reported by O'Sullivan in patients diagnosed as having gestational diabetes, only 2% of whom still had abnormal oral glucose tolerance postpartum, and the results of our patients, all of whom had IGT after pregnancy. In spite of differences of technique and in the populations studied, the prevalence of IGT and overt diabetes at follow-up was significantly less in the Aberdeen series, who were initially a higher risk group. It seems probable that this is mainly attributable to dietary treatment in the follow-up period as O'Sullivan's cases were treated only during pregnancy.
Explore the source record for details and available documents.
A new and specific method is used for the measurement of plasma free fatty acids (FFA) in pregnancy. Fasting plasma FFA and glucose concentrations were measured serially in twenty normal and twelve overweight women in pregnancy and related to infant birth weight. Large variation between individuals was noted for FFA and no change was found with advancing gestation. Studies of the day-to-day variation in the same women at 20 and 36 weeks gestation showed wide variations in concentrations. No significant change in glucose concentration was noted with advancing gestation, but postnatal values were significantly higher. Small variability of glucose concentrations was noted in both the serial and day-to-day studies. In normal-weight women a positive correlation between the observed birth weight of their infants and the fasting plasma glucose levels was found at 20 and 40 weeks and also with the mean of 5 levels measured in pregnancy. No similar correlation was found for the group of overweight women.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Glibornuride is an addition to the second-generation sulphonylureas, that has been shown in clinical trials to be effective and non-toxic. Twenty-three diabetics who were poorly controlled on other oral hypoglycaemic agents and seven newly diagnosed diabetics were treated with glibornuride. The efficacy and lack of toxicity of this drug was confirmed, but there was no evidence to suggest that it is significantly more potent than other sulphonylureas. It does not seem to represent a significant therapeutic advance.
Explore the source record for details and available documents.
More information is needed about the "natural history" of early diabetes mellitus. A report is presented of the progress over one to nine years of 72 patients who formed the control group of a clinical trial of chlorpropamide and placebo in the management of subclinical diabetes. Most patients showed no deterioration of carbohydrate tolerance, and only four (5.6%) progressed to overt diabetes. The findings of other published series are reviewed. Studies of the effect of treatment of early diabetes must be large scale and long term, and an untreated control group must be included to prevent apparent improvement in carbohydrate tolerance being wrongly attributed to the effect of therapy.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
The intravenous glucose tolerance test (I.V.G.T.T.) was used to diagnose chemical diabetes during pregnancy in 180 women, 50 of whom subsequently received chlorpropamide therapy in a daily dosage of 100 mg; the remainder had no drug therapy.Preliminary work showed the I.V.G.T.T. to be reproducible in the second and third trimesters but not in the puerperium in normal pregnancy. Though intravenous glucose tolerance deteriorates between the second and third trimesters in women with no features of diabetes, a significant improvement occurs after a course of chlorpropamide in a daily dosage of 100 mg during pregnancy in chemical diabetes, but this treatment did not enhance the rate of return to normal glucose tolerance post partum.Plasma glucose and insulin studies showed no evidence of hypoglycaemia or hyperinsulinism in the mother at delivery or in the newborn when chlorpropamide had been used compared with a group receiving no such treatment. In the infants of the chlorpropamide-treated mothers there was a suggestion of an increased rate of glucose disposal in response to a glucose challenge, but no increase in birth weight.There were two fetal deaths in the 50 pregnancies of mothers treated with chlorpropamide, one being due to a mistaken premature delivery and the other to a diaphragmatic hernia. Thus chlorpropamide in a dose of 100 mg a day has been shown to reverse chemical diabetes diagnosed and treated in pregnancy without apparent risk to the fetus.