LATS actions of bacterial permeability and protein synthesis.
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Biomedical subjects
Publications and source records attributed to T D Hockaday.
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Intravenous glucose tolerance was measured at diagnosis and during the subsequent 10 years in 103 Type 2 diabetic patients not treated with insulin. KG (the rate constant for clearance of intravenous glucose) was inversely related to fasting plasma glucose at all review times (at diagnosis being Rs = -0.77, p less than 0.001), and at times to the circulating concentrations of ketone bodies (at diagnosis being Rs = -0.52, p less than 0.001) and glycerol (Rs = -0.29, p less than 0.01). In the first year of treatment, most metabolic abnormalities improved. One to 10 years after diagnosis, fasting glucose concentration and intravenous glucose tolerance deteriorated (median glucose from 6.4 to 7.4 mmol l-1, p less than 0.001; median KG from 0.81 to 0.69% min-1, p less than 0.01). Likewise, the 'homeostatic model assessment' of insulin insensitivity deteriorated (median from 2.3 to 3.7 arbitrary units, p less than 0.001) over the same period but first-phase insulin secretion remained steady or improved. This suggests that increases in insulin insensitivity have a predominant effect on slowly deteriorating glucose tolerance from 1 to 10 years after diagnosis in Type 2 diabetes.
The most appropriate way to estimate islet B-cell function in Type 2 diabetes is unclear, and this has led to many different techniques of measurement being used. We have examined the associations to two fasting and four glucose-stimulated indices of islet B-cell function in members of a group of 249 Type 2 patients, seeking correlations with concurrent glucose tolerance and antilipolytic effect, and with subsequent clinical outcome. The six B-cell indices were interrelated to variable degrees (rs -0.21 to +0.92). Early glucose-stimulated insulin output (incremental 1st-phase insulin area) was not significantly positively correlated with the fasting plasma concentration of immunoreactive insulin at any time. Fasting immunoreactive insulin and 'minimal model' islet B-cell parameters were poorly related to the rate constant for glucose clearance and the degree of antilipolysis (rs values between -0.13 and +0.40). Homeostatic model assessment of the fasting islet B-cell function was more consistently related to these metabolic effects. Incremental first-phase insulin area was the islet B-cell index most consistently related to metabolic abnormalities (rs up to +0.56), and to subsequent need for oral hypoglycaemic or exogenous insulin therapy. No index of islet B-cell function was consistently associated with the subsequent development of diabetic tissue damage.
Eight Type 2 diabetic patients ate and prepared five different meals at home, taking each meal on two separate occasions. They measured their blood glucose just before eating and 30, 60, 120, and 180 min after the meal. The meals varied in energy and dietary fibre content and in the ratio (by energy) of carbohydrate to fat. Total energy content of the meals had little effect on the postprandial glycaemic responses nor were the responses reduced by meals with high dietary fibre content. The ratio of carbohydrate to fat did not significantly affect postprandial glycaemic responses when meals were low in fibre. However, postprandial glycaemic responses were significantly greater in the meal with a high ratio of carbohydrate to fat, high in fibre and low in energy compared with those after the equicaloric meal low in carbohydrate to fat ratio and low in fibre (area under the curve 683 +/- 131 vs 306 +/- 55 mmol l-1 min-1, p < 0.05). Fat intake of 35% of energy may be compatible with improved postprandial blood glucose concentrations. Many meal combinations need to be studied in order to provide reliable information for diabetic patients. The method outlined proved producible (within patient coefficient of variation 13%), easy to perform and inexpensive.
Nine diabetic patients who were receiving various treatments supplemented their normal home diets (two patients) or metabolic ward diets (seven patients) with guar crispbread for five days. Their mean urinary glucose excretion fell significantly by 38% during the last two days. A significant fall in fasting blood glucose concentration of 1.1 +/- 0.4 mmol/1 (19.8 +/- 7.2 mg/100 ml) was seen only in those who took guar after the control period. Over eight weeks' treatment insulin dosage was reduced by 21% in five patients, and home testing showed that glycosuria was reduced by 68% in six patients. Guar crispbread is likely to be a useful adjunct to diabetic treatment irrespective of the type of treatment or insulin dosage used.
Vibration sensory thresholds (VSTs) were estimated in 40 healthy subjects and 8 with diabetic peripheral neuropathy. A vibrameter and a biothesiometer were used at four sites and at differing pressures. In normal subjects, with the vibrameter at 200 g, mean VST +/- SE for all sites was 1.87 micron +/- 0.22 and at 400 g dropped to 1.08 micron +/- 0.15 (P less than .0001). In 20 of these subjects with a biothesiometer at 200 and 400 g, mean VST fell from 12.8 +/- 1.5 to 11.1 +/- 1.1 (arbitrary units) (P = .01) when the greater pressure was applied. In the 8 subjects with peripheral neuropathy, with the vibrameter at 200 and 400 g, respectively, mean VST fell from 70.7 +/- 26 to 7.2 +/- 1.8. VST in these subjects was estimated again after 1 mo and showed strong correlations with the previous values. Biothesiometer results correlated with vibrameter results at all sites. Thus, VST decreases as the pressure of the applied stimulus is increased and this effect appears to be more marked in peripheral neuropathy. This has important consequences in monitoring this condition.