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J M Burrin

Publications and source records attributed to J M Burrin.

159 records · Page 9Linked to original sources

Simple filter paper method for home monitoring of blood glucose, lactate, and 3-hydroxybutyrate.

Previous methods for assessing the control of diabetes at home have concentrated on the measurement of glucose concentrations in urine and, more recently, blood. These levels reflect only one aspect of deranged metabolism in the disease. A technique is described whereby glucose, lactate, and 3-hydroxybutyrate can be measured in capillary blood samples dried on boric acid impregnated filter paper. The technique is sufficiently sensitive to measure 0.05 mmol/l glucose, 0.02 mmol/l lactate, and 0.004 mmol/1 3-hydroxybutyrate with precisions of 4.0%, 4.5%, and 8.0%, respectively. This method could prove useful in the broader metabolic assessment of the diabetic state.

3-Hydroxybutyric Acid↗

Automated colorimetric estimation of glycosylated haemoglobins.

The measurement of glycosylated haemoglobin is now widely used as a guide to glycaemic control in patients with diabetes mellitus. Present methods for measurement of glycosylated haemoglobin are either laborious, expensive or both. We describe a precise and inexpensive method for the automated analysis of glycosylated haemoglobin based on a colorimetric technique. The within-batch coefficient of variation ranged from 2.0 to 4.8% and between-batch was less than 11.0%. At least 200 samples can be analysed per day.

Colorimetry↗

Hyperinsulinaemia in hyperprolactinaemic women.

The metabolic sequelae of hyperprolactinaemia were studied over a 12 h period of normal meals and activity in nine young females hyperprolactinaemic subjects and fourteen matched controls. In the patients, fasting blood glucose and serum insulin concentrations were normal, as was the blood glucose response to meals; the insulin rise with meals was, however, exaggerated and hyperinsulinaemia persisted throughout the day (mean +/- SEM 12 h serum insulin, 26 +/- 8 vs. 16 +/- 9 mu/l, P < 0.01). Blood lactate, pyruvate and alanine response to meals was also increased. Blood glycerol (mean 12 h blood glycerol 0.06 +/- 0.01 vs. 0.09 +/- 0.01 mmol/l, P < 0.01) and blood 3-hydroxybutyrate (mean 12 h blood 3-hydroxybutyrate 0.03 +/- 0.01 vs. 0.05 +/- 0.01 mmol/l, P < 0.05) concentrations were lower in hyperprolactinaemic subjects. There was a strong negative correlation between mean insulin and mean 3-hydroxybutyrate levels in the afternoon period (rs = -0.92, P < 0.01). Excess circulating prolactin in young female is associated with normoglycaemic hyperinsulinaemia. The changes in blood metabolite levels observed are probably secondary to the increased insulin concentrations.

Adult↗

Role of residual insulin secretion in protecting against ketoacidosis in insulin-dependent diabetes.

The role of preserved beta-cell function in preventing ketoacidosis in type I insulin-dependent diabetes was assessed in eight patients with and seven patients without residual beta-cell function as determined from C-peptide concentrations. After 12 hours of insulin fatty-acid, and glycerol concentrations were all significantly higher in patients without beta-cell function than in those with residual secretion. Mean blood glucose concentrations reached 17.2 +/- SE of mean 1.3 mmol/l (310 +/- 23 mg/100 ml) in the first group compared with 8.8 +/- 1.4 mmol/l (159 +/- 25 mg/100 ml) in the second (P less than 0.01), while 3-hydroxybutyrate concentrations rose to 5.5 +/- mmol/l (57 +/- 5 mg/100 ml) and 1.4 +/- 0.3 mmol/l (15 +/- 3 mg/100 ml) in the two groups respectively (P less than 0.01). Individual mean C-peptide concentrations showed a significant inverse correlation with the final blood glucose values (r = -0.91; P less than 0.02). These findings strongly suggest that even minimal residual insulin secretion is important for metabolic wellbeing in diabetes and may prevent the development of severe ketoacidosis when insulin delivery is inadequate.

Adolescent↗

Comparison between human 125I-labelled TSH labelled with lactoperoxidase or chloramine-T; advantages in the use of enzymically labelled antigen in a radioimmunoassay for human TSH.

1. Human thyroid stimulating hormone (human TSH) was iodinated by both chloramine-T and lactoperoxidase methods. 2. Human 125I-labelled TSH prepared by the enzymic method showed less damage on storage, an increased shelf-life, and improved binding at different antiserum dilutions. 3. A comparison of the values of the bound counts on the addition of human TSH, expressed as a percentage of the zero standard bound counts (B/BO values) in the standard curves, demonstrated that lactoperoxidase-labelled human TSH gave increased sensitivity.

Chloramines↗

The pituitary-thyroid axis in severe falciparum malaria: evidence for depressed thyrotroph and thyroid gland function.

Abnormal thyroid function is strongly associated with mortality in severe non-thyroidal illness. We have assessed the pituitary-thyroid axis serially in 18 Thai adults with severe falciparum malaria and in 18 matched controls. The admission total serum thyroxine (T4) concentrations of the patients (median [range]: 64 nmol/litre [less than 30-91]) were significantly lower than those of controls (81 nmol/litre [61-133]; 2P less than 0.01), and remained depressed until after fever and parasite clearance. Two patients who died in hospital had admission serum T4 concentrations less than 35 nmol/litre. The admission basal serum thyrotropin (TSH) levels of the patients (0.9 mU/litre [less than 0.2-3.1]) were similar to those of controls (1.3 mU/litre [less than 0.2-3.7], 2P greater than 0.1) and remained normal throughout fever and parasitaemia. Thirty-minute TSH increments during a thyrotropin-releasing hormone test on admission were reduced in 13 patients with severe malaria (4.1 mU/litre [0.7-8.1]) relative to those in convalescence (7.1 mU/litre [1.7-14.4], n = 10, 2P less than 0.01) and controls (5.6 mU/litre [3.3-12.9], n = 9, 2P less than 0.05). These findings suggest that thyrotroph and thyroid gland function are depressed during acute, severe malaria. As these changes may be an adaptation to accelerated catabolism, the role of thyroid replacement in such patients is uncertain.

Adolescent↗

Hormonal and metabolic responses in brittle diabetic patients during feedback intravenous insulin infusion.

Twenty-four hour profiles of blood hormones and intermediary metabolites were obtained in seven 'brittle' diabetic subjects during their usual insulin therapy and during feedback intravenous insulin infusion from an artificial pancreas (GCIIS). The results were compared to those in matched stable diabetics and normal controls. Although routine insulin doses were higher in the brittle group than in the stable group (164 +/- 32 (mean +/- SE) vs. 58 +/- 8 U/day, P less than 0.005) during routine therapy, plasma free insulin levels were equal (35 +/- 12 vs. 31 +/- 6 mU/l). In the brittle group feedback i.v. insulin infusion reduced daily requirements to normal levels (80 +/- 13 U/day, P less than 0.025; stable group 71 +/- 4 U/day, NS). On routine therapy blood glucose levels were not different in the two groups (brittle 10.5 +/- 1.6, stable 10.8 +/- 0.6 mmol/l) and were similarly corrected by the GCIIS (6.9 +/- 0.3 and 6.9 +/- 0.3 mmol/l, respectively). Blood lactate and pyruvate levels were markedly abnormal in the brittle group during routine therapy (lactate: brittle group 1.93 +/- 0.27 mmol/l, stable group 0.91 +/- 0.07 mmol/l, P less than 0.025), and this abnormality was not corrected by the GCIIS (1.75 +/- 0.32 and 0.88 +/- 0.08 mmol/l, P less than 0.005). Abnormalities were also found in profiles of blood alanine and glycerol, and serum cortisol. Blood ketone body levels did not differ between the two groups of patients. The results suggest a defect in insulin delivery from subcutaneous tissue into the plasma. These patients have a characteristic metabolic abnormality, unresponsive to short-term normoglycaemia, either as the result of long-term disturbance of diabetic control, or as a marker for the underlying hormonal or biochemical abnormality.

3-Hydroxybutyric Acid↗

Leptin in pituitary adenomas--a novel paracrine regulatory system.

A growing number of physiological and pathophysiological processes have been shown to be influenced by leptin apart from its first recognised role as a modulator of hypothalamic appetite and weight control centers. We investigated the presence and pattern of distribution of leptin mRNA and the mRNA of the long isoform of the leptin receptor in the normal pituitary and in different types of pituitary adenomas. We also studied leptin secretion from human pituitary tumors in culture, and the in vitro pituitary hormone release following stimulation with human leptin. Leptin mRNA expression was detected at a low level of expression in 50% of tumors but in none of the normal pituitaries. By immunohistochemistry, leptin was present in occasional scattered cells in the normal pituitary and in pituitary tumors. The leptin receptor long isoform was detected in the majority (65%) of pituitary tumors and in all normal pituitaries. It did not segregate with any particular tumor type, and varying levels of expression were detected between the tissues studied. 34% of pituitary adenomas showed leptin release into the incubation media during in vitro culture. Leptin mRNA, the mRNA of the long isoform of the receptor, or in vitro leptin release, did not correlate with tumor type or with any of the other pituitary hormones released. In vitro leptin stimulation of pituitary tumors caused stimulation of FSH and a-subunit secretion from a non-functioning adenoma and TSH secretion from a somatotroph adenoma. As the co-localisation of ACTH and leptin in corticotroph cells was previously suggested, we investigated whether in vivo ACTH release is accompanied by a simultaneous plasma leptin level rise (i) in peripheral plasma samples after food intake-induced ACTH rise in healthy obese and nonobese individuals and (ii) in petrosal sinus samples after CRH injection in Cushing's disease patients. Our data suggest that a rise in ACTH levels is not accompanied by detectable rise in leptin levels in peripheral and in petrosal sinus blood samples. In summary, leptin is synthesized and stored within the pituitary and may modulate other pituitary hormone secretion, although probably it does not contribute to plasma leptin level changes. Pituitary leptin may therefore be a novel paracrine regulator of pituitary function.

Adenoma↗

Serum IGF-1 concentration in diabetic retinopathy.

Growth factors such as growth hormone and insulin-like growth factor 1 (IGF-1) may be important in the pathogenesis of diabetic retinopathy. We measured serum IGF-1 in 371 diabetic patients attending a diabetic retinopathy clinic and in 73 non-diabetic control subjects. No significant difference was observed in IGF-1 level between the diabetic and control groups (168 +/- 3.9 vs 177 +/- 7.4 micrograms/l [mean +/- SE]). Within the diabetic group, there was no difference between patients with no retinopathy and those with proliferative change (198.7 +/- 8.8 vs 190.5 +/- 11 micrograms/l). After adjusting for differences in age, duration of diabetes, and presence of proteinuria, only the inactive previously proliferative group showed any significant difference from the other patient subgroups (151.8 +/- 11.5 micrograms/l; p less than 0.05). Serum IGF-1 correlated with age in the control group (r = 0.49; p less than 0.001) and to a lesser extent in the diabetic group (r = -0.23; p less than 0.05). IGF-1 levels were higher in patients with proteinuria than in those without proteinuria (196.8 +/- 10.3 vs 138.8 +/- 4.4 micrograms/l; p less than 0.001).

Blood Glucose↗

A comparative study of the activity of biosynthetic human insulin and pork insulin using the glucose clamp technique in normal subjects.

The activity of biosynthetic human insulin (BHI) has been compared with that of pork insulin using the glucose clamp technique in normal subjects. After a baseline period, insulin was infused at 0.02 U/kg/h for 2 h, then 0.032 U/kg/h for 2 h, and finally 0.05 U/kg/h for 2 h. Glucose was clamped at baseline values using a glucose-controlled insulin infusion system (Biostator) and the amount of glucose infused to maintain normoglycemia calculated for each insulin dose for the two insulins. C-peptide levels decreased with both insulins, suggesting suppression of endogenous insulin secretion. Serum insulin levels attained were the same for both insulins. There were no significant differences in either total glucose infused or glucose infused during the last 30 or 60 min at each insulin dose for the two insulins. Intermediary metabolite responses to the infusion of the two insulins were similar. We conclude that in normal human beings, BHI shows identical metabolic activity with pork insulin.

Adult↗

A crossover comparison of continuous subcutaneous insulin infusion (CSII) against multiple insulin injections in insulin-dependent diabetic subjects: improved control with CSII.

Ten insulin-dependent C-peptide-negative diabetic subjects, whose control had been optimized on twice-daily injection therapy, were treated for periods of 10 wk in a crossover study, with either a thrice-daily subcutaneous insulin injection regimen (Actrapid + Ultratard) or by continuous subcutaneous insulin infusion (CSII). On CSII insulin dose stabilized at 51 +/- 5 U/day, compared with 80 +/- 9 U/day (P = 0.004) on the thrice-daily injection regimen, having been 60 +/- 6 U/day on twice-daily therapy. After 10 wk glycosylated hemoglobin was 11.7 +/- 0.6% on injection therapy and 10.0 +/- 0.7% (P = 0.026) on CSII. Mean blood glucose concentration and urinary glucose excretion were lower at most points during the study on CSII than on injection therapy. Patients on pumps gained weight compared with the thrice-daily injection regimen (P = 0.023 at 10 wk) and the previous twice-daily regimen, despite the reduction in insulin dose. Considering individual patients, four markedly improved on CSII compared with the previous twice-daily regimen and five compared with Actrapid + Ultratard. No patient showed impaired control on CSII compared with either injection regimen. The benefits of portable insulin infusion pumps over injection therapy are thus clearly demonstrable under outpatient conditions even with equal and intensive medical attention.

Adult↗

Comparison of the activity and pharmacokinetics of porcine insulin and human insulin (Novo) as assessed by the glucose clamp technique in normal and diabetic man.

Using the glucose clamp technique, human insulin (Novo) and natural porcine insulin were found to have identical potency in terms of glucose delivery in the second hour of i.v. infusion at low (0.02 U/kg/h; 265 +/- 25 versus 232 +/- 35 mg/min, respectively) and high (0.05 U/kg/h; 467 +/- 47 versus 452 +/- 41 mg/min, respectively) doses in normal man. Insulin metabolic clearance rates, serum in vivo half-life, and rate of onset of action were also similar. In insulin-dependent diabetic subjects, whose blood glucose levels were also held constant by feedback glucose infusion, the free insulin profiles after s.c. injection of neutral soluble human insulin and porcine insulin (0.2 U/kg) were identical, and similar to those after conventional and highly purified bovine insulin preparations. Glucose requirement to maintain normoglycemia for the first 5 h after injection was 49.6 +/- 8.2 g for conventional bovine insulin, 50.4 +/- 10.0 g for highly purified bovine, 40.5 +/- 6.9 g for human insulin, and 50.6 +/- 12.4 g for porcine insulin (NS by analysis of variance). No difference in insulin activity was detected when glucose requirement was expressed in terms of the prevailing free insulin concentration. Responses of blood intermediary metabolite levels were indistinguishable between all insulins in both studies.

Adult↗