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Biomedical subjects

T D Hockaday

Publications and source records attributed to T D Hockaday.

At least 19 recordsLinked to original sources
PubMed1992

Adipose tissue metabolism in obesity: lipase action in vivo before and after a mixed meal.

Physiological actions of insulin include suppression of fat mobilization from adipose tissue and activation of adipose tissue lipoprotein lipase. Here, we report measurements of adipose tissue hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) action in vivo in 10 normal and eight obese subjects, with the latter group having varying degrees of glucose intolerance. HSL and LPL actions (per gram of adipose tissue) were similar in the two groups, after an overnight fast. In the normal subjects, HSL action was suppressed after a meal (by 75% +/- 6% between 60 to 300 minutes, P less than .01), and the action of LPL was increased (clearance of circulating triacylglycerol [TAG] increased by 140% +/- 57% at 300 minutes, P less than .05). Despite hyperinsulinemia, these responses were blunted in the obese subjects (P less than .05 for each change being less than in normal group). The adipose tissue of the obese subjects showed continued nonesterified fatty acid (NEFA) release at a time when NEFA mobilization was completely suppressed in the normal group. Both impaired suppression of HSL and low fractional retention of fatty acids for reesterification within the adipose tissue contributed to this abnormal NEFA release. Impaired activation of LPL was associated with a greater absolute increase in plasma TAG concentration postprandially in the obese. In obese subjects, adipose tissue HSL and LPL fail to respond to immunoreactive insulin postprandially, which may be an important maladaptation in terms of lipoprotein metabolism and risk of coronary heart disease.

Adipose Tissue↗
PubMed1992

The ketosis-resistance in fibro-calculous-pancreatic-diabetes. 1. Clinical observations and endocrine-metabolic measurements during oral glucose tolerance test.

We measured circulating levels of C-peptide, pancreatic glucagon, cortisol, growth hormone and metabolites (glucose, non-esterified fatty acids, glycerol and 3-hydroxybutyrate) in fibro-calculous-pancreatic diabetic (FCPD, n = 28), insulin-dependent diabetic (IDDM, n = 28) and non-diabetic control (n = 27) subjects during an oral glucose tolerance test. There was no difference in the two diabetic groups in age (FCPD 24 +/- 2, IDDM 21 +/- 2 years, mean +/- SEM), BMI (FCPD 16.0 +/- 0.6, IDDM 15.7 +/- 0.4 kg/m2), triceps skinfold thickness (FCPD 8 +/- 1, IDDM 7 +/- 1 mm), glycaemic status (fasting plasma glucose, FCPD 12.5 +/- 1.5, IDDM 14.5 +/- 1.2 mmol/l), fasting plasma C-peptide (FCPD 0.13 +/- 0.03, IDDM 0.08 +/- 0.01 nmol/l), peak plasma C-peptide during OGTT (FCPD 0.36 +/- 0.10, IDDM 0.08 +/- 0.03 nmol/l) and fasting plasma glucagon (FCPD 35 +/- 4, IDDM 37 +/- 4 ng/l). FCPD patients, however, showed lower circulating concentrations of non-esterified fatty acids (0.73 +/- 0.11 mmol/l), glycerol (0.11 +/- 0.02 mmol/l) and 3-hydroxybutyrate (0.15 +/- 0.03 mmol/l) compared to IDDM patients (1.13 +/- 0.14, 0.25 +/- 0.05 and 0.29 +/- 0.08 mmol/l, respectively). This could be due to enhanced sensitivity of adipose tissue lipolysis to the suppressive action of circulating insulin and possibly also to insensitivity of hepatic ketogenesis to glucagon. Our results also demonstrate preservation of alpha-cell function in FCPD patients when beta-cell function is severely diminished, suggesting a more selective beta-cell dysfunction or destruction than hitherto believed.

3-Hydroxybutyric Acid↗
PubMed1991

Central rather than generalized obesity is related to hyperglycaemia in Asian Indian subjects.

The relationship of body mass index and waist-hip ratio with plasma glucose concentrations during an oral glucose tolerance test (OGTT) was studied in native Indian (Asian) subjects. A total of 389 subjects (131 non-diabetic, 74 impaired glucose tolerant (IGT) and 184 Type 2 diabetic (newly diagnosed and untreated] were studied. Prevalence of obesity (BMI greater than or equal to 27.0 kg m-2 in men and greater than or equal to 25.0 kg m-2 in women, 21% and 47%, respectively) was lower in people with Type 2 diabetes than that reported in white Caucasian and migrant Asian populations. Body mass index was highest in IGT subjects (26.1 (19.7-34.3) kg m-2, median (5-95th centile] and was higher in diabetic subjects (24.2 (19.3-32.2) kg m-2) than in non-diabetic control subjects (23.5 (17.1-30.0) kg m-2). However, waist-hip ratio was higher in both IGT (0.88 (0.75-0.98)) and diabetic subjects (0.88 (0.75-1.00)) than in non-diabetic control subjects (0.83 (0.70-0.97)), with no difference between the hyperglycaemic groups. On multivariate analysis, fasting as well as 2-h plasma glucose concentrations during OGTT were found to be related to waist-hip ratio (p less than 0.01) and subscapular fat thickness (p less than 0.01) but not to body mass index (or triceps fat thickness). Thus, in native Indians central obesity seems to be a more important association of hyperglycaemia than generalized obesity.

Abdomen↗
PubMed1991

Factors controlling fat mobilization from human subcutaneous adipose tissue during exercise.

To investigate possible factors that limit fat utilization during exercise, arteriovenous differences of plasma nonesterified fatty acids (NEFA) and glycerol were measured across the subcutaneous adipose tissue of the anterior abdominal wall in nine subjects who exercised for 60 min at 50-70% of their maximal O2 consumption. The large gradient of NEFA concentration from adipose tissue venous to arterial plasma increased throughout the exercise period. Maximal plasma NEFA concentrations in adipose venous drainage were reached postexercise (median 3,800 mumol/l), with a median NEFA-to-albumin molar ratio of 5.7. Fractional reesterification of fatty acids within the tissue (assessed from the ratio of NEFA to glycerol release) was 20-30% in the basal state and declined during exercise. After exercise there was apparently negative reesterification, implying release of NEFA retained in adipose tissue during exercise. Although these findings challenge current views on the regulation of NEFA release, they are in agreement with the concept of supply of fatty acids from adipose tissue as the major factor limiting fat oxidation during sustained exercise.

Adipose Tissue↗
PubMed1991

Breath hydrogen excretion or plasma acetate levels during the lactulose tolerance test?

Since both acetate and hydrogen are produced by colonic bacterial fermentation, the clinical utility of the measurement of either parameter in nine subjects for the lactulose tolerance test was tested. The fasting plasma acetate concentration (mean +/- s.d., mmol/l) of 0.11 +/- 0.06 increased to peak levels between 150 min (0.23 +/- 0.12) and 180 min (0.23 +/- 0.09), both P less than 0.01, after ingesting 20 g lactulose. In one subject with previous gastrectomy and intestinal hurry, the peak was at 30 min. Mean post-lactulose acetate levels (0.21 +/- 0.09) were higher than fasting levels (P less than 0.03). Breath hydrogen excretion exhibited a similar trend. Indeed, a significant correlation (rs 0.39, P less than 0.01) was demonstrated between the acetate and hydrogen values. It is therefore concluded that patients for the lactulose breath test show fairly similar changes in plasma acetate and breath hydrogen excretion after lactulose ingestion. Either measurement could thus be used in assessing colonic fermentation in humans.

Acetates↗
PubMed1991

The formation of acetate from ethanol with and without prior chlorpropamide intake in diabetic and non-diabetic subjects.

It has been suggested that raised post-ethanol plasma acetaldehyde levels, from inhibition of aldehyde dehydrogenase, underlie the liability to chlorpropamide, alcohol flushing (CPAF). We tested the hypothesis that acetate formation from acetaldehyde, the reaction catalysed by that enzyme, was also likely to be affected by chlorpropamide (CP) medication. In six healthy non-diabetic 'non-flushers', fasting acetate (Ac +/- s.d. mmol/l) was 0.22 +/- 0.12, and increased by 0.47 +/- 0.14 to peak levels by 30 min after intake of 40 ml dry sherry, which increased plasma ethanol (mmol/l) levels to 10.2 +/- 6.0. After 5 days of CP (250 mg daily), fasting Ac (0.17 +/- 0.05) and increase to peak of Ac and ethanol after 40 ml sherry (0.56 +/- 0.12 and 8.9 +/- 7.2 respectively), were not changed (P n.s.). There was no correlation between Ac and ethanol at any time point. When the studies were repeated in five non-insulin-dependent diabetic 'flushers', both on regular CP medication and after 3 days without CP, there was again no significant difference in fasting and post-ethanol Ac levels between the two studies (fasting 0.18 +/- 0.04 v. 0.17 +/- 0.02, and increase to peak 0.62 +/- 0.13 v. 0.72 +/- 0.18, P n.s.). These results indicate that the conversion of ethanol to acetate is unaffected by CP medication, and furthermore that post-ethanol acetate levels do not predict liability to CPAF.

Acetates↗
PubMed1990

Arteriovenous differences across human adipose and forearm tissues after overnight fast.

Measurements of arteriovenous differences across subcutaneous abdominal tissue (mainly adipose) and deep forearm tissue (mainly muscle) were made on 25 occasions in normal subjects after an overnight fast. Adipose tissue was shown to be strongly lipolytic (releasing nonesterified fatty acids and glycerol), to clear circulating triacylglycerol, glucose, ketone bodies and acetate, and to produce lactate. Uptake of circulating carbohydrate and ketones was sufficient to account for only 51% of the adipose tissue oxygen consumption, implying that adipose tissue utilizes fuel(s) stored within it. The mean fractional re-esterification rate of fatty acids in adipose tissue was 13% to 19%. Arteriovenous differences were converted to fluxes of carbon atoms to compare the movements of different fuels. (Amino acids were not included in these calculations.) Adipose tissue after an overnight fast was a net exporter of carbon, whereas in resting muscle the uptake of carbon atoms from circulating carbohydrate and lipid fuels approximately balanced the CO2 production. Fatty acids were the main form in which carbon left adipose tissue, and the main source of carbon atoms entering the resting forearm.

Acetates↗
PubMed1990

Acetate tolerance and the kinetics of acetate utilization in diabetic and nondiabetic subjects.

We investigated acetate utilization in humans by randomly intravenously infusing acetate (2.5 mmol/min) or bicarbonate (2.8 mmol/min) over 60 min into nine nondiabetic and six non-insulin-dependent diabetic subjects followed with or without bolus intravenous glucose (20 g/m2 body surface area). The acetate metabolic clearance rate (MCR) was greater in the nondiabetic subjects (50.4 +/- 14.9 vs 25.0 +/- 6.5 mL.min-1.kg-1, p less than 0.01) as were acetate elimination rate constant (Kac) (0.031 +/- 0.003 vs 0.026 +/- 0.004/min, p less than 0.01) and basal turnover rate (8.56 +/- 3.65 vs 4.92 +/- 1.03 mumol.min-1.kg-1, p less than 0.01); acetate half-time was thus shorter in the nondiabetics (22.6 +/- 2.2 vs 27.2 +/- 3.8 min, p less than 0.01). Kac was reduced and half-time was prolonged in all the subjects (p less than 0.001) when glucose was available. Prior acetate or bicarbonate infusion had no influence on either the KG rate constant of glucose elimination or the postglucose insulin responses in both subject groups. These results suggest that the infused acetate did not worsen glucose tolerance, glucose impaired acetate utilization unlike reported in ruminants, and acetate is rapidly metabolized in humans although at a slower rate in diabetics.

Acetates↗
PubMed1990

Cellular sodium influx is low in type 1 (insulin dependent) diabetes.

Leucocyte sodium influx was studied in 29 type 1 (insulin dependent) diabetic subjects and compared to 24 non diabetic controls matched for age, body mass index and blood pressure. Total sodium influx from a low external concentration ((Na+) = 10 mmol/l) was reduced in type 1 diabetes (0.23 vs 0.31 mmol/l/min, p less than 0.05) as was amiloride insensitive sodium influx (0.09 vs 0.13 mmol/l/min, p less than 0.01). No difference was found in amiloride sensitive flux. No ionic flux was correlated with plasma glucose or insulin concentrations or with HbA1 levels. Intracellular sodium accumulation in type 1 diabetes is not due to an increase in total sodium influx, as judged from an external concentration of 10 mmol/l.

Adult↗
PubMed1979

High-carbohydrate diets and insulin-dependent diabetics.

A high-carbohydrate-(HC)-modified fat diet was compared with a standard low-carbohydrate (LC) diabetic diet in 11 insulin-dependent diabetics. Basal and preprandial plasma glucose concentrations were appreciably lower when the patients received the HC diet derived chiefly from readily available cereal and vegetable sources (mean (+/- SE of mean) basal concentrations 6.7 +/- 1.2 mmol/l (121 +/- 22 mg/100 ml) with the LC diet and 4.3 +/- 0.7 mmol/l (77 +/- 13 mg/100 ml) with the HC diet; mean preprandial concentrations 11.1 +/- 1.2 mmol/l (200 +/- 22 mg/100 ml) LC diet and 8.9 +/- 1.3 mmol/l (160 +/- 23 mg/100 ml) HC diet). total and low-density lipoprotein cholesterol concentrations were lower when patients took the HC diet (mean 4.4 +/- 0.2 and 2.4 +/- 0.2 mmol/l (189 +/- 8 and 124 +/- 8 mg/100 ml) respectively), and the ratio of high-density lipoprotein cholesterol to total cholesterol tended to rise. The average percentage of glycosylated haemoglobin did not differ between the two diets. Thus several measures of carbohydrate and lipid metabolism appear to be more satisfactory when patients receive a HC diet, which is an acceptable alternative to that still recommended to most insulin-requiring patients.

Adult↗
PubMed1979

Improved glucose control in maturity-onset diabetes treated with high-carbohydrate-modified fat diet.

Fourteen patients with established maturity-onset diabetes were treated as outpatients with a high-carbohydrate-(about 60% of total daily energy requirements)-modified fat diet (ratio of polyunsaturated fatty acids to other fatty acids greater than or equal to 1:1) for six weeks. Commercially available and acceptable cereal foods and tuberous vegetables high in both digestible and non-digestible carbohydrates were used. Simple sugars were restricted. Compared with their usual, low-carbohydrate diabetic diet this diet resulted in a fall in basal plasma glucose concentration (average of values measured at 0300, 0500, and 0700), mean preprandial plasma glucose concentration (average of values measured at 0800, 1230, and 1730), and percentage of glycosylated haemoglobin. Modifying dietary fat also decreased the fasting plasma cholesterol concentration. The findings suggest that it is no longer justifiable to prescribe a low-carbohydrate diet for maturity-onset diabetes.

Blood Glucose↗
PubMed1979

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↗
PubMed1979

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↗