A competitive radioimmunoassay for the quantitative determination of glycated haemoglobin was developed. The antiserum, obtained by immunizing guinea pigs with reduced glycated human albumin, was capable of identifying and quantitating the glucitollysine residues of glycated Hb after reduction with sodium borohydride. To simplify the sample preparation we introduced...
While it has very recently been reported that tumour induced hypoglycaemia is characterised by elevated production of insulin-like growth factor 2, the tissues responsible for induction of hypoglycaemia are largely unknown. We have investigated a patient with a large retroperitoneal mass and spontaneous hypoglycaemia. When compared to a reference population the patient displayed...
Ling Zhi-8 (LZ-8), a novel and recently discovered immunomodulatory protein having in vivo immunosuppressive activity, was tested for in vivo effect against Type 1 (insulin-dependent) diabetes mellitus in the non-obese diabetic mouse, the disease having immunologically mediated aetiology in this animal. LZ-8 had mitogenic activity in vitro towards spleen cells of the non-obese...
In NOD mice, 50–70% of females and 10–20% of males develop diabetes, although almost all the animals show insulitis. To see if environmental insults could induce diabetes in subjects with pre-clinical anti-Beta cell autoimmunity, non-diabetic NOD mice were selected and injected with a sub-diabetogenic dose of streptozotocin at 6 or 20 weeks of age. The streptozotocin failed to...
SummaryThe main therapeutic indication for glucagon is the treatment of hypoglycaemia in insulin overdosed Type 1 (insulin-dependent) diabetic patients. We have previously shown that an intranasal spray of 7.5 mg glucagon with deoxycholic acid as surfactant was able to correct an i.v. insulin-induced hypoglycaemia in diabetic patients. However, bioavailability and stability...
The use of tritiated glucose tracers may result in underestimation of glucose turnover during hyperinsulinaemic clamps giving paradoxical negative endogenous glucose production rates. While mathematical modelling errors in the analysis of tracer data are major determinants of this underestimate in the non-steady state, the relative importance of tracer contamination under these...
SummaryIn 10 patients with Type 1 (insulin-dependent) diabetes mellitus gastric emptying of a digestible solid and liquid meal was measured during euglycaemia (blood glucose concentration 4–8 mmol/l) and during hyperglycaemia (blood glucose concentration 16–20 mmol/l). Gastric emptying was studied with a scintigraphic technique and blood glucose concentrations were stabilised...
To determine the reproducibility of the first phase insulin response to intravenous glucose, ten normal subjects underwent two intravenous glucose tolerance tests separated by at least two weeks. Intravenous dextrose (0.3 g/kg) was administered over 2 min by continuous infusion and arterialised-venous samples were taken from a retrogradely cannulated hand vein in the opposite arm...
SummaryTo demonstrate the myo-inositol depletion hypothesis in hyperglycaemia-induced embryopathy, rat conceptuses of 9.5 days of gestation in the early head-fold stage were grown in vitro during neural tube formation for 48 h with increasing amounts of glucose. The effects of an aldose reductase inhibitor and the myo-inositol supplementation were also investigated. Sorbitol and...
Neural tube defects in infants of diabetic mothers constitute an important and frequent cause of neonatal mortality/morbidity and long-term chronic handicaps. The mechanism by which normal neural tube fusion occurs is not known. The failure of rostral neural tube fusion seen in mouse embryos incubated in the presence of excess-D-glucose can be significantly prevented by the...
SummaryIn normal man, several hormonal and metabolic adjustments allow the maintenance of the blood glucose concentration within narrow limits. Hyperglycaemia participates in this regulation via stimulation of glucose disposal and inhibition of glucose production. The effects are mediated, in addition to changes in insulin and glucagon secretion, by the mass-action effect of...
Placental isoferritin is produced by activated T lymphocytes and may, therefore, be considered as a manifestation of T cell involvement. Placental isoferritin is measured using CM-H-9 monoclonal antibody which binds exclusively to placental isoferritin. Placental isoferritin has been determined in the serum of 80 patients with Type I (insulin-dependent) diabetes mellitus, 100...
SummaryPotential risk factors have been examined for association with mortality over a 10–12 year follow-up of the patients of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics (aged 35–54 year in at entry to the study). Proteinuria has the strongest association with all-cause mortality in univariate analysis being significant in patients of both...
To evaluate the effect of combined kidney and pancreas transplantation on insulin action and glucose metabolism, 15 Type 1 (insulin-dependent) diabetic patients who were undergoing combined kidney-pancreas transplantation were studied before transplantation by means of the euglycaemic hyperinsulinaemic clamp technique combined with 3-3H-glucose infusion and indirect calorimetry...
SummaryThe 497 members of the London Cohort of the WHO Multinational Study of Vascular Disease in Diabetics have been followed for mortality from 1975 to 1987. During this period 92 patients died. The most common cause of death was myocardial infarction: 36 (39.1%) deaths, heart disease was responsible for 51.1% of deaths and all cardiovascular disease for 55.4%. Neoplastic...
