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Biomedical subjects

T D Hockaday

Publications and source records attributed to T D Hockaday.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1990

Application of minimal models to measuring insulin sensitivity.

Bergman's minimal model of glucose dynamics was used to analyse intravenous glucose tolerance tests in non-diabetic and non-insulin dependent diabetic subjects (NIDDM). This analytical approach yielded an index of insulin sensitivity in 63% of the non-diabetic and 15% of NIDDM subjects. When the model was constrained to search for the most likely parameter solutions, all the non-diabetic and 96% of the diabetic plasma insulin-glucose curves could be solved. A comparison of the insulin sensitivity index derived from this constrained minimal model against the metabolic clearance rate of glucose during a hyperinsulinaemic clamp carried out on the same subjects showed a correlation of 0.84 (P less than 0.01, N = 12 normal subjects) and 0.65 (P less than 0.001, N = 21 NIDDM patients). We conclude that this modification of the minimal model may improve the number of intravenous glucose tolerance tests capable of systematic analysis in NIDDM subjects, giving a measure of insulin sensitivity that correlates with more established measures of this parameter.

Blood Glucose↗
PubMed1990

Intravenous glucose tolerance and mortality in non-insulin-dependent diabetes mellitus.

Two hundred and forty-nine patients with non-insulin-dependent diabetes were entered into a prospective study at diagnosis and examined at presentation and one, three, and five years later. Ten years after diagnosis, 34 patients were known to be dead and 214 alive. A number of factors were significantly associated with survival on univariate analysis and appeared to form two independent intra-related groups: a 'metabolic' group and a 'degenerative condition' group. Multivariate analysis of these two groups showed that glucose tolerance (the rate constant KG for decrease in plasma glucose concentration after its intravenous injection) was significantly related to survival in the 'metabolic' group, and age, blood pressure and anti-hypertensive therapy were significant in the 'degenerative' group of factors. A low KG value was more strongly associated with prognosis than any other factor. Values from the one year review were prognostically more useful than initial or later values. Indices of insulin secretion were similar irrespective of whether patients survived or died, and so we believe the lower KG values of dead patients were due to impaired insulin sensitivity. A regression equation using the above factors correctly allocated survival outcome in 81% of subjects.

Blood Glucose↗
PubMed1989

The relationship of plasma acetate with glucose and other blood intermediary metabolites in non-diabetic and diabetic subjects.

In investigating the interrelations of plasma acetate with glucose metabolism, we established that fasting plasma acetate levels (mmol/l) were greater in the diabetic than non-diabetic individuals (p less than 0.001). Plasma acetate and glucose levels correlated in all subjects (non-diabetic and diabetic) as a whole (rs 0.28, p less than 0.0001) and in the diabetics alone (rs 0.35, p less than 0.001). After i.v. glucose (20 g/m2 body surface area), plasma acetate levels increased further in the diabetic and non-diabetic individuals. Plasma acetate also increased when non-diabetic individuals consumed 75 g oral glucose. Moreover, while plasma acetate levels had returned to fasting values by 90 min in the non-diabetic subjects after oral and i.v. glucose, levels remained elevated in the diabetics after i.v. glucose. The K rate constant of glucose elimination after i.v. glucose in the diabetics correlated negatively with acetate values at many time points. In the non-diabetics, changing acetate and glucose levels after oral glucose also correlated at multiple time points. These results suggest that the plasma acetate level is influenced by variations in glycaemia and provide further evidence for an impaired rate of acetate metabolism in diabetes.

Acetates↗
PubMed1989

Effects of insulin on human adipose tissue metabolism in vivo.

1. The metabolic effects of insulin on human adipose tissue were studied by combining the euglycaemic clamp technique with measurement of arteriovenous differences across the subcutaneous adipose tissue of the anterior abdominal wall. 2. Eight normal subjects were studied after an overnight fast, and for 120 min during infusion of insulin (mean arterialized plasma insulin 50-55 m-units/l). 3. During the insulin infusion, the arterialized and abdominal venous levels of both non-esterified fatty acids and glycerol fell, and the arteriovenous differences for the release of these substances narrowed. The fractional rate of re-esterification of fatty acids was around 20% in the fasting state and increased to almost 100% during hyperinsulinaemia. 4. In the fasting state the uptake of glucose and 3-hydroxybutyrate by adipose tissue could account for only 20% of the oxygen uptake. During insulin infusion, adipose tissue glucose uptake increased and could account for more than 100% of oxygen uptake, implying storage of glucose. 5. Net balances of different substrates across adipose tissue were examined by calculating fluxes in terms of microgram-atoms of carbon. In the fasting state adipose tissue was in marked negative carbon balance (because of the export of non-esterified fatty acids); during insulin infusion it just reached 'carbon balance'. These results were in contrast to those from a previous study of glucose ingestion, in which the adipose tissue showed marked positive carbon balance (net substrate deposition).

3-Hydroxybutyric Acid↗
PubMed1989

The effect of environmental temperature on prandial changes in leucocyte sodium transport in man.

Cellular sodium transport via the Na+, K+-ATPase contributes significantly to daily energy expenditure. The effect of a meal on leucocyte Na+ transport and intracellular electrolytes was therefore investigated in lean normal subjects at room temperatures of 23 degrees and 33 degrees, to determine if the Na pump responds to the need for thermogenesis. In the fasting state, the ouabain-sensitive efflux rate which reflects active Na+ transport, and the intracellular electrolytes were similar. At 2 h after eating a 4.2 MJ (1000 kcal) meal, the ouabain-sensitive efflux rate constant rose when the room temperature was 23 degrees but not at 33 degrees. The ouabain-sensitive Na+ efflux rate, an index of active Na+ transport, rose post-prandially at 23 degrees only. The post-prandial activation of leucocyte active Na efflux in normal subjects was blunted at higher environmental temperatures, when the need for thermogenesis was reduced.

Adult↗
PubMed1989

Change in plasma acetate levels in diabetic subjects on mixed high fiber diets.

When 10 diabetic (five insulin-dependent) subjects with reasonable glycemic control were randomized from their usual (U) diet (about 30 g fiber/day) between two different but isocaloric high fiber diets, each sequentially over 6 wk [HF (55 g fiber/day) and HFS (55 g fiber/day with sucrose taken as 15 g three times daily, with meals)], plasma acetate (mmol/L) increased by 35% on both high fiber diets from 0.21 +/- 0.06 (SD) to 0.28 +/- 0.10 (HF) and 0.30 +/- 0.10 (HFS) (both p less than 0.01). This was higher than the random weekly variation in plasma acetate levels of 11% in six other glycemically stable diabetic patients. When the acetate value was expressed as acetate/glucose, i.e., relative to the fasting glucose level (since fasting levels of acetate and glucose consistently positively correlate), the increase was about 80%. Fasting plasma non-esterified fatty acid (NEFA) levels fell during the high fiber diets and correlated negatively with the fasting acetate level (rs -0.51, p less than 0.005). The fall in NEFA and rise in acetate levels appeared greatest with the sucrose-supplemented meals. These results suggest increased exogenous contribution to the plasma acetate level from increased colonic fermentation of dietary fiber and raise the possibility of using such measurements in the assessment of compliance to high fiber diets. The fall in NEFA levels associated with raised plasma acetate levels may contribute to the beneficial effects on glycemic control observed with the high fiber diets.

Acetates↗
PubMed1989

Glycaemic control affects cellular sodium metabolism.

Total and amiloride sensitive leucocyte sodium influx in Media containing 10 mmol/l Na was studied directly using a triple isotope method for measuring initial 22Na uptake rates in 25 non insulin dependent diabetic subjects. Glycaemic control was assessed by glycated haemoglobin and fasting blood glucose. Although no significant relationship between Na flux and either plasma insulin or blood glucose could be found, glycated haemoglobin was significantly correlated with both total and amiloride sensitive flux. Glycaemic control must be considered in future work on cellular sodium metabolism.

Amiloride↗
PubMed1988

Leucocyte sodium efflux and electrolyte content in insulin treated diabetes.

Leucocyte sodium efflux and sodium content were studied in 41 insulin treated diabetic patients and compared to 41 age, body mass index and blood pressure matched nondiabetic control subjects. Fasting leucocyte 22Na ouabain-sensitive efflux rate constants were lower in diabetic patients (median [range] 2.30 [1.04-3.73] versus 2.45 [1.57-3.95] h-1, p less than 0.4) suggesting a reduced sodium pump activity. The 22Na ouabain-insensitive efflux rate constant which reflects passive sodium efflux was raised in insulin treated diabetes (0.92 [0.42-1.73] versus 0.79 [0.28-1.49] h-1, p less than 0.01). Leucocyte sodium content was raised in the diabetic patients (47.7 [26.9-93.4] versus 26.5 [15.9-67.7] mmol/kg, p less than 0.0001). Abnormal cellular sodium handling could lead to hypertension or other complications in diabetes.

Adult↗
PubMed1988

The effect of Intralipid infusion on the human leucocyte sodium-pump in vivo.

1. The effect of unsaturated long-chain non-esterified fatty acids (NEFA) on the human leucocyte sodium-pump was studied in vivo. 2. Plasma NEFA level was raised acutely from 0.28 (SD 0.10) to 2.54 (SD 0.48) mmol/l by infusion of 'Intralipid 20%' (trademark) at 90 ml/h with heparin, and the human leucocyte 22Na efflux rate constants were studied in eight normal weight males. 3. After 3 h, there was a significant lowering of the total (from 3.97 (SD 0.92) to 3.10 (SD 0.71)/h; P less than 0.01) and ouabain-sensitive 22Na efflux rate constants (from 2.89 (SD 0.55) to 2.37 (SD 0.62)/h; P less than 0.02). Ouabain-insensitive efflux rate constants showed a tendency to fall (from 1.08 (SD 0.51) to 0.73 (SD 0.23)/h). Leucocyte potassium content remained unchanged, but sodium content rose from 31 (SD 12) to 38 (SD 18) mmol/kg dry weight (P less than 0.05). Total, ouabain-insensitive and ouabain-sensitive efflux rates did not change significantly during the Intralipid-heparin infusion. 4. Plasma insulin levels rose gradually throughout the 3 h infusion period. 5. In conclusion, NEFA, when raised to pathological levels, can inhibit the leucocyte Na-pump in vivo even in the presence of physiological levels of serum albumin, and may increase insulin secretion.

Biological Transport, Active↗
PubMed1987

Leucocyte sodium pump activity after meals or insulin in normal and obese subjects: cause for increased energetic efficiency in obesity?

As cellular sodium pumping is an energy consuming process and differences in the obese may account for their energetic efficiency, leucocyte sodium-22 efflux was studied in obese and normal volunteers both in the fasting state and after a test meal or infusion of glucose and insulin intravenously. The 22Na ouabain sensitive efflux rate constant was significantly higher in obese subjects than normal (mean (1 SD) 2.69 (0.40)/h v 2.35 (0.49)/h). Two hours after a 4.2 MJ (1000 kcal) meal there was an increase in the efflux rate constant from its fasting value in normal weight subjects (2.39 (0.33)/h to 2.71 (0.40)/h) but not in obese subjects (2.65 (0.54)/h to 2.61 (0.58)/h). The rise in ouabain sensitive efflux rates was significantly higher in normal than obese subjects. Both groups showed a rise in intracellular sodium concentrations. The euglycaemic clamp produced similar results. Feeding or infusion of insulin increases sodium pump activity more in normal than obese subjects. This difference may contribute to any defective dietary thermogenesis in obesity, which may lead to energetic efficiency and a tendency to gain weight.

Adult↗