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Biomedical subjects

T D Hockaday

Publications and source records attributed to T D Hockaday.

At least 109 records · Page 6Linked to original sources

Lipid abnormalities in untreated maturity-onset diabetics and the effect of treatment.

Plasma cholesterol and serum triglyceride levels and frequency of lipoprotein abnormalities were investigated in 126 untreated maturity-onset diabetics and 126 age- and sex-matched control subjects. Serum triglyceride levels were higher (mean: 1.67 mmol/l) and type IV hyperlipoproteinaemia occurred more frequently (16.7%) in the diabetic group as compared with the controls (1.29 mmol/l and 4.8% respectively). These findings were not explained by an excessive frequency of renal disease, hypertension or drug treatment amongst the diabetics. Normal men showed higher serum triglyceride (mean: 1.36 mmol/l) and lower plasma cholesterol (mean: 5.6 mmol/l) levels than normal women (1.21 mmol/l and 6.4 mmol/l respectively). No sex difference was seen amongst the diabetics. Triglyceride levels fell after one month of dietary treatment but only remained lowered in diabetics who required sulphonylureas for glycaemic control. After treatment for one year the correlation between serum triglycerides and blood glucose rose from r = 0.15 (NS) before treatment to r = 0.43 (p less than 0.001). Similarly the correlation between serum triglycerides and ponderal index rose from r = 0.19 (NS) to r = 0.28 (p less than 0.02).

Body Weight↗

Direct animal and indirect human evidence of altered platelet function in diabetics.

All agree on altered platelet function in vitro (and increasingly in vivo) in diabetics of substantial duration and/or with clinical evidence of angiopathy. However, a platelet abnormality earlier in the disease remains uncertain. Three sets of data from Oxford will be reviewed: (1) Observations of Honour on platelet aggregation at sites of minimal injury within blood vessels of anesthetized rabbits, with greater sensitivity to superfused ADP when hyperglycemia has followed alloxan only days previously. This increased aggregatability (not hyperglycemia determined) is reversed by a few days of insulin treatment or by dipyrimadole (alone or with synergistic acetyl salicylic acid): (2) Beta-thromboglobulin is released from platelets and is increased in venesected blood from diabetics after a standardized procedure (no prostaglandin E1 in anticoagulant) with final radioimmunoassay. Results in diabetics after surgery, etc., will also be presented, and (3) in a prospective study of newly-diagnosed, mostly maturity-onset type diabetics, an increase in plasma fibrinogen (thrombin coagulation of plasma, controlled against normals) was observed during the first 3 yr, largely due to males treated with sulfonylureas; decreases in platelet count and in prothrombin concentration were also statistically significant.

Adenosine Diphosphate↗

Insulin deficiency and insulin resistance interaction in diabetes: estimation of their relative contribution by feedback analysis from basal plasma insulin and glucose concentrations.

The liver and beta cells function in a negative feedback loop, which appears to have a predominant role in regulating both the basal plasma glucose and insulin concentrations. The degree of basal hyperglycemia in diabetes probably provides a bioassay of both the effect of a reduction in insulin secretory capacity and the degree of insulin resistance. A mathematic model of the interaction of insulin deficiency and insulin resistance has been constructed, based on the known response characteristics of the beta cells to glucose, and of plasma glucose and insulin control of hepatic and peripherpal glucose flux. The degree to which beta cell deficiency increases basal plasma glucose reflects the hyperbolic shape of the normal insulin secretory response to different glucose concentrations. The height of basal plasma insulin is a function of the degree of insulin resistance. From the basal plasma insulin and glucose concentrations, the model provides an estimate of the degree to which both beta cell deficiency and insulin resistance contribute to diabetes. The predictions arising from the model are in accord with experimental data in man and in animals. In normal-weight diabetics who do not have increased insulin resistance, the model predicts that more than 85% of beta cell function has to be lost for the basal plasma glucose to rise to 6 mmol/liter, but a further 5%--10% loss increases the basal plasma glucose to over 10 mmol/liter. In a third of a consecutive series of 65 newly presenting, uncomplicated diabetics, both normal weight and obese, the analysis from the model suggested that insulin resistance, rather than beta cell deficit, was the predominant feature.

Blood Glucose↗

Plama-thromboglobulin concentrations in diabetes mellitus.

Abnormally high plasma-concentrations of the platelet protein thromboglobulin were demonstrated in a group of 72 diabetic patients. The highest concentrations were found in patients with clinical evidence of tissue damage. Many diabetic patients, without such complications have elevated thromboglobulin levels, and this blood abnormality may predate recognisable clinical lesions.

Adenosine Diphosphate↗

Diabetic dimorphism according to acetylator status.

Two groups of diabetics and 19 normal controls had their rate of acetylation of sulphadimidine measured. Among 47 patients with maturity onset diabetes the 29 fast acetylators were older at diagnosis and, at a given glucose concentration, had a higher pretreatment fasting insulin concentration than slow acetylators. They also had a larger first-phase insulin secretion in response to intravenous glucose both before and after one month's dietary treatment. The greatest difference between fast and slow acetylators was in the first-phase secretion of insulin after a month's treatment. The proportion of fast acetylators among the second group of diabetics, who had been admitted to improve their glucose concentrations or for treatment of tissue damage, was similar to that among the normal controls (50% and 47% respectively). The data seem to indicate that diabetics are fast acetylators unexpectedly often, but it is not clear whether the dimorphism according to acetylator status produces a differential risk of neuropathy or of any other type of diabetic tissue damage.

Acetylation↗

Prospective comparison of modified fat-high-carbohydrate with standard low-carbohydrate dietary advice in the treatment of diabetes: one year follow-up study.

1. A prospective randomized study of two dietary regimens has been started in newly-diagnosed diabetics to determine their effect on circulating metabolites and on diabetic complications. 2. During the first year of treatment the fasting plasma glucose concentrations on both the low-carbohydrate diet and the high-carbohydrate, modified-fat (MF) diet showed a similar decrease. 3. Plasma cholesterol showed a sustained decrease only in patients recommended a MF diet. Transient changes in plasma triglyceride concentrations occurred in patients on both dietary regimens. 4. Increased plasma cholesterol levels are associated with atheromatous disease which is common in diabetics in Europe and North America. A MF diet may therefore have an advantage in that it lowers the plasma cholesterol as well as being effective in lowering the plasma glucose.

Adult↗

Treatment of diabetes with guar gum. Reduction of urinary glucose loss in diabetics.

When nine diabetic patients supplemented either their normal home diets (four patients) or metabolic ward diets (five patients) with 25 g guar gum daily for 5 or 7 days their mean urinary glucose excretion fell by 46% (P less than 0-05) and 54% (P less than 0-01), respectively. Gel-forming,, unabsorbable carbohydrate may therefore be a useful adjunct to anti-diabetic therapy, irrespective of the type of treatment or insulin dosage used.

Adult↗

Hormonal and metabolic responses to glucagon in diabetes mellitus.

The metabolic and hormonal responses to glucagon (1 mg, subcutaneous) were studied in twelve diabetic and twelve non-diabetic subjects. Diabetics showed a GH response, which although commencing slightly earlier, did not otherwise differ from that of the controls. There was the expected diminished insulin response to glucagon among the patients on oral agents. The GH response to glucagon in the diabetics began before there was any significant fall in blood glucose (BG). The hyperglycaemic response in the diabetics peaked later, was greater in amplitude and was more prolonged. In this group both pyruvate and lactate changes were delayed and diminished in amplitude. The diabetics showed a biphasic response of both acetoacetate and 3-hydroxybutyrate to glucagon; a small transient significant rise in the first 2 h followed by a second rise after 3h. In contrast the controls showed a significant fall in these metabolites during the initial 2 h, before a rise after 3 h. The significance of these hormonal and metabolic responses is discussed.

Acetoacetates↗

The synergistic effect of aspirin and dipyridamole upon platelet thrombi in living blood vessels.

In rabbits previously injected i.v. with alloxan, serial observations of platelet thrombus formation in response to topical adenosine diphosphate (ADP) at sites of electrical injuries in pial arteries have been made. Using this model we have studied the effects of oral daily doses of dipyridamole (Persantin) and acetyl salicylic acid (ASA) upon platelet thrombus formation. Oral daily doses of 42 mg of ASA and 6 mg dipyridamole given separately in alloxan-treated rabbits are without effect. When given together orally, 42 mg and 6 mg respectively reduced the level of sensitivity to ADP for producing platelet thrombi to that established for the rabbits before the injection of alloxan. But withdrawal of these combined doses of dipyridamole and ASA caused the sensitivity of ADP for platelet thrombus formation to be raised to the much increased level present in rabbits soon after they are given i.v. alloxan. This apparent synergistic behaviour displayed by dipyridamole and ASA in these rabbits results in antithrombotic effects which are clearly absent when these two agents are given separately. It is of interest that the dose levels used here are equivalent, an a body weight ratio, to those being used in man in the current Persantin-Aspirin Reinfarction Study.

Adenosine Diphosphate↗

Unabsorbable carbohydrates and diabetes: Decreased post-prandial hyperglycaemia.

Two test meals were taken in random order on separate days by 8 non-insulin-requiring diabetic volunteers after 14-hour overnight fasts. Addition of 16 g guar and 10 g pectin to the control meal containing 106 g carbohydrate decreased markedly and significantly the rise in blood-glucose between 30 and 90 minutes and also resulted in significantly lower insulin levels between 30 and 120 minutes. When these meals were fed to 3 insulin-dependent diabetic subjects, a similar flattening of the post-prandial glucose rise ensued. This addition of certain forms of dietary fibre to the diet of diabetics significantly decreases post-prandial hyperglycaemia and would be expected to improve the control of blood-glucose concentration.

Blood Glucose↗