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Biomedical subjects

I Hanning

Publications and source records attributed to I Hanning.

At least 19 recordsLinked to original sources
PubMed1991

The effects of human proinsulin on glucose turnover and intermediary metabolism.

We compared the effects of human proinsulin and human insulin on glucose disposal, suppression of hepatic glucose production (HGP), and intermediary carbohydrate and lipid metabolism. Six young, lean, subjects underwent eight separate euglycemic clamps with low-dose intravenous (IV) infusions of insulin and proinsulin (four each). The insulin infusions gave steady-state levels of 0.08 +/- 0.004 (I1), 0.12 +/- 0.003 (I2), 0.18 +/- 0.07 (I3), and 0.25 +/- 0.06 nmol/L (I4). The proinsulin infusions were chosen to give steady-state levels approximately 20-fold higher on a molar basis than insulin, based on previous findings that proinsulin has only 5% to 10% the biological potency of insulin. Steady-state proinsulin levels were 1.2 +/- 0.04 (P1), 2.8 +/- 0.07 (P2), 4.5 +/- 0.3 (P3), and 6.9 +/- 0.3 nmol/L (P4). HGP was suppressed equally by proinsulin and insulin at the four dose levels. Percentage elevation of glucose disposal was significantly increased during each of the insulin infusions compared with proinsulin: I1 107% +/- 4%, P1 87% +/- 4% (P = .03); I2 143% +/- 7%, P2 125% +/- 12% (P = .01); I3 238% +/- 38%, P3 173% +/- 22% (P = .03); I4 283% +/- 17%, P4 178% +/- 11% (P = .002). Dose-response curve analysis demonstrated that proinsulin stimulated glucose disposal approximately 3.3% compared with insulin. The effectiveness of proinsulin in suppressing HGP was approximately 5% compared with insulin. Plasma nonesterified fatty acids, blood glycerol, and 3-hydroxybutyrate were suppressed by similar amounts during each of the four insulin and proinsulin doses.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Progress in immunoassays for serum prolactin: evidence from the UK External Quality Assessment Scheme (EQAS) 1980-1989.

The quality of serum prolactin assays routinely performed by UK laboratories has been monitored in an external quality assessment scheme (EQAS) over a 10-year period, during which participation in the EQAS increased three-fold, and considerable changes in methods and standardization were introduced. The all-laboratory mean was used as the sample target value, and proved to be stable and accurate. Overall between-laboratory agreement in the clinically important range improved from a geometric coefficient of variation (GCV) of 25% to 14%. This appears to reflect the increased use of kits in place of 'in-house' assays, the more widespread availability of international standards and the absence of any marked differences in bias between the commonly used methods. Published guidelines on the clinical interpretation of prolactin values should, therefore, be widely applicable. The EQAS data indicate that, in general, the quality of performance of prolactin assays is adequate for their clinical application.

Antibodies, Monoclonal↗
PubMed1991

External quality assessment of immunoassays of peptide hormones and tumour markers: principles and practice.

External quality assessment schemes (EQAS) have traditionally emphasised the achievement of between-laboratory consensus. Although this is important, the application of EQAS to relatively new and evolving techniques such as immunoassay calls for a wider and more searching remit if the goals of accurate assays, properly used, are to be achieved. This article outlines the principles of EQAS for peptide hormones and tumour markers, emphasising key aspects such as validation of target values, dependency of results on sample type, and assessment of method characteristics such as vulnerability to interfering factors. The latter are considered to be important as they can affect patient care more seriously than modest degrees of imprecision or inaccuracy. EQAS play a unique role in providing objective data on assays performed in many laboratories under routine conditions and the data they provide can guide improvement in diagnostic reagents and laboratory practice.

Artifacts↗
PubMed1989

Progress and problems in immunoassays for serum pituitary gonadotrophins: evidence from the UK external quality assessment schemes, (EQAS) 1980-1988.

Trends in the quality of assays for serum gonadotrophins performed by laboratories in the UK EQAS during the 1980s are reviewed, with particular reference to the effects of the recent introduction of immunometric assays (IMA) as an alternative to radioimmunoassay (RIA). IMA gave results which were on average 17% higher than RIA for FSH, and 33% lower for LH. These bias characteristics were not entirely accounted for by differences in assay standardisation, but appeared to reflect the different isoforms of the hormones detected by the monoclonal antibodies used in the IMA. Between-laboratory agreement remained, consequently, unsatisfactory overall (geometric coefficient of variation, GCV, 20-30%), although good within method groups (GCV 10%). IMA were less vulnerable to non-specific background interference than many RIA, and could avoid interference from HCG. Some IMA were, however, vulnerable to interference from heterophilic antibodies in patients' sera. The differences between RIA and the various IMA in numerical values reported, and in their vulnerability to interferences underline the need for care in interpreting assay results.

Animals↗
PubMed1988

Quality of performance of assays for serum growth hormone in the United Kingdom (UK): evidence from the UK external quality assessment scheme, 1980-1987.

The performance of laboratories in the UK External Quality Assessment Scheme for growth hormone (GH) during the years 1980 to 1987 is reviewed. The number of participating laboratories has increased steadily and is at present 67; about one half use immunoradiometric assay (IRMA) kits and the use of such kits is increasing at the expense of 'in-house' radioimmunoassays (RIAs). The consensus mean, which is used as the target value for assessing performance, has remained accurate and reproducible against this changing background. The between-laboratory geometric coefficient of variation has remained at about 18% during the period reviewed, revealing unsatisfactory between-laboratory agreement. This is in part due to poor within-laboratory performance in a small proportion of laboratories but it is also due to the negative bias of some IRMA kits. Most IRMA kits do appear, however, to provide marginally better within-laboratory precision than RIA, and are less vulnerable to non-specific interference. The laboratory interpretation of results was assessed from time to time, and was generally satisfactorily performed. In an attempt to identify the causes of poor performance, a detailed survey of assay methods and laboratory practice has been carried out; the results are described in an associated report [1].

Growth Substances↗
PubMed1988

Factors associated with the quality of laboratory performance in the United Kingdom external quality assessment scheme for serum growth hormone.

A search was made for associations between poor performance in the UK External Quality Assessment Scheme (EQAS) for serum growth hormone (GH), and a range of factors including assay method, laboratory workload and staffing, and Internal Quality Control (IQC) procedures. On the basis of the factors identified as being associated with poor performance we recommend the following. 1. Laboratories using RIA for GH should routinely analyse samples at two dilutions and report a mean result. 2. The use of 125I-GH which is 5 or more weeks old should be avoided. Tracer should also be chromatographed to remove aggregate before use. 3. Laboratories using RIA should avoid using a standard curve which covers too wide a range concentration; a curve midpoint (ie GH concentration to reduce the zero standard binding by 50%) of about 8 mU/l or less is probably acceptable. 4. It should be noted that high workloads present a risk of some loss in quality of responsible for checking IQC data. 6. Laboratories which do not have the resources to maintain fully their own RIA as outlined above should carefully consider use of an unbiased, precise IRMA. The UK EQAS has identified two assays (Boots-Celltech Sucrosep, NETRIA) that appear to meet these criteria [2]. The above observations may also be relevant to immunoassays for other peptide hormones.

Growth Substances↗
PubMed1988

Pancreatic beta-cell function in CAPD.

Pancreatic beta-cell function was evaluated in uraemic patients by measuring beta-cell peptides in the peripheral blood after intravenous glucagon (1 mg) stimulation. Patients in chronic renal failure, patients on haemodialysis, and both new and established subjects on continuous ambulatory peritoneal dialysis (CAPD) (10 in each group) were studied and compared to 8 healthy controls. Fasting glucose (3.6-4.4 mmol/l) and insulin concentrations (9.5-11.7 mU/l) were normal and did not differ between the uraemic groups, but c-peptide concentrations were markedly increased in uremia (1.84-2.38 nmol/l) compared to controls (0.48 nmol/l). Following glucagon stimulation an exaggerated blood glucose response with delayed glucose peak was observed, while the peak insulin response to glucagon was normal; however, the return to basal concentrations was delayed in uraemia. The c-peptide response was also exaggerated and peak concentrations in uraemic subjects (3.0-4.3 nmol/l) were significantly greater than controls (1.5 nmol/l). The response of CAPD patients was similar to those on haemodialysis and non-dialysed uraemic patients. The abnormalities seen were due to uraemia, and CAPD treatment had no specific adverse effect on beta-cell function. Thus, from this data there was no evidence that CAPD per se is detrimental to beta-cell integrity.

C-Peptide↗
PubMed1988

Quality of performance of assays for maternal serum alphafetoprotein in the United Kingdom: evidence from the UK external quality assessment scheme 1980-87.

Between-laboratory agreement in the UK EQAS for maternal serum alphafetoprotein has improved steadily since 1976 and the geometric coefficient of variation is now 8 to 9% at levels of 50 to 150 kU/L. The use of a common standard and commercial assay kits appear to have contributed to this trend. Within-laboratory performance is also generally good, about 50% of participants maintain a bias of less than 5%, together with a scatter of the bias of less than 10%. These data indicate that the quality of assay performance is adequate for the requirements of screening programmes for open neural tube effects. The improvement in laboratory performance is such that between-laboratory agreement is better expressed in kU/L than as multiples of the median. Errors in interpretation of clearly normal or abnormal results appear to be rare (0.4%), and contribute little to overall false positive and negative rates. However, they assume significance as most are due to avoidable errors.

Female↗
PubMed1987

Basal and 24-h C-peptide and insulin secretion rate in normal man.

An understanding of the metabolic abnormalities rising from inappropriate insulin delivery in diabetic patients demands a knowledge of 24-h and basal insulin secretion rates in normal man. We have used biosynthetic human C-peptide to determine its kinetic parameters in 10 normal subjects and applied these to measurements of plasma concentrations in the same subjects to determine pancreatic secretion rate. Metabolic clearance rate measured by stepped primed infusion of biosynthetic human C-peptide at rates of 10, 19 and 26 nmol/h was 4.7 +/- 0.7 (+/- SD) ml X kg-1 X min-1, and was independent of infusion rate. Fractional clearance (T1/2, 26 +/- 3 min) and distribution volume (0.178 +/- 0.039 l/kg) were calculated from the decline in concentration after cessation of the highest rate infusion. Basal insulin secretion calculated from the C-peptide metabolic clearance rate and plasma concentrations for the period 02.00 to 07.00 hours was 1.3 +/- 0.4 U/h. Over 24 h total insulin secretion on a standard high carbohydrate diet was 63 +/- 15 U, calculated from the area under the C-peptide concentration curve. Basal insulin secretion, therefore, accounted for 50 +/- 8% of total insulin secretion. Although only 5.6 +/- 1.1% of C-peptide was detected in 24-h urine collections, urinary C-peptide excretion was significantly related to 24-h C-peptide secretion (r = 0.74, p less than 0.02).

Adult↗
PubMed1987

Parenteral nutrition effect on serum insulin in the preterm infant.

Blood glucose and serum insulin levels were measured in two groups of preterm infants that had been matched for gestational age. Both groups were fed parenterally during the first 72 hours of life and were mechanically ventilated because of respiratory distress syndrome. Group A infants (n = 11) received 10% glucose (infusion rate 5 mg/kg/min) and group B infants (n = 12) received amino acid solution (1.2 g/kg/d) in addition to 10% glucose at the same rate as those in group A. Infants in both groups received 90 mL/kg of fluid per day. There was no difference in blood glucose or serum insulin levels between the two groups 24 hours after beginning the infusion; however, at 48 hours there was a significantly (P less than .01) higher insulin level in infants receiving amino acid and glucose infusion compared with those receiving only glucose. Blood glucose level remained stable in both groups. We conclude that, in the stable preterm infant, the higher insulin level associated with continuous amino acid infusion does not result in hypoglycemia.

Amino Acids↗
PubMed1986

Metabolic abnormalities in children of non-insulin dependent diabetics.

Non-insulin dependent diabetes appears to be an inherited condition. A study of young offspring of non-insulin dependent diabetics was conducted to determine whether metabolic abnormalities could be found at a young age before clinical diabetes developed. Thirteen patients with non-insulin dependent diabetes were selected who fulfilled the following criteria: they had a sibling who also had non-insulin dependent diabetes, their spouse was non-diabetic, and the offspring were aged between 12 and 45 years, not diabetic, and available for study. All 32 offspring had a 75 g oral glucose tolerance test, and results in 13 of them, one randomly selected from each family, were compared with 13 controls of similar age, sex, and weight. The offspring had significantly higher fasting concentrations of glucose, higher proportions of haemoglobin A1, and higher concentrations of insulin, C peptide, and glucagon. After glucose challenge the increases in both glucose and C peptide concentrations were significantly greater in the offspring. These differences were maintained in all 32 offspring when compared with 18 controls of similar age, sex, and weight; seven of the 32 offspring had impaired glucose tolerance. These results indicate that young offspring of selected non-insulin dependent diabetics can show extensive metabolic changes including impaired glucose tolerance. These changes are associated with hyperinsulinaemia and hyperglucagonaemia.

Adolescent↗
PubMed1986

The metabolic response to insulin deprivation in idiopathic brittle diabetes.

To test the hypothesis that frequent episodes of ketoacidosis and severe hyperglycaemia in brittle diabetes result from an exaggerated response to insulin withdrawal, the metabolic response to insulin deprivation in 16 severely brittle female diabetics has been compared with that in 6 C-peptide negative stable female diabetic patients of similar age and body weight. 4 hr after stopping insulin infusion, blood glucose was significantly higher in the brittle diabetics (22.8 vs 17.0 mmol/l, p less than 0.001) but blood 3-hydroxybutyrate was not different (1.8 vs 1.6 mmol/l). Concentrations of free insulin and counter-regulatory hormones were similar, basally and during the deprivation. Insulin antibody levels were significantly elevated in the brittle patients (11.2 vs 5.2 mmol/l, p less than 0.05) and there was no relationship between glucose or ketone body response and antibody level. Blood lactate, pyruvate, alanine and glycerol were significantly elevated basally in the brittle diabetic patients, but did not respond differently to insulin deprivation. Basal lactate and pyruvate concentrations were significantly correlated with overnight insulin requirements (lactate, rs 0.62, p less than 0.05; pyruvate, rs 0.70, p less than 0.05) suggesting that the elevated basal concentrations resulted from the higher peripheral insulin delivery rates required to maintain overnight normoglycaemia in the brittle patients. We conclude that although there are demonstrable abnormalities of intermediary metabolism in brittle diabetics, neither elevated levels of counter-regulatory hormones, nor an exaggerated response to insulin withdrawal explains the frequent episodes of ketoacidosis in these patients.

3-Hydroxybutyric Acid↗
PubMed1986

Human ultralente insulin: a comparison with porcine lente insulin as a twice-daily insulin in insulin-dependent diabetic patients with fasting hyperglycaemia.

Six C-peptide-deficient diabetic patients, selected because of raised fasting blood glucose concentrations, participated in a randomised cross-over trial comparing twice-daily porcine soluble plus human ultralente with porcine soluble plus porcine lente insulins. As out-patients, overall mean blood glucose concentrations before and after breakfast were significantly lower during human ultralente therapy (7.2 +/- 0.8 vs 12.0 +/- 1.3, 11.1 +/- 1.0 vs 14.3 +/- 1.0 mmol/l, p less than 0.05), but were unchanged for the rest of the day. During overnight in-patient metabolic profiles a nadir in blood glucose occurred between 2-4 am with both insulin regimens (5.2 +/- 0.9 mmol/l ultralente, 6.5 +/- 1.3 mmol/l lente). Mean fasting and post-breakfast blood glucose levels were significantly lower with human ultralente as were fasting concentrations of glycerol and non-esterified fatty acids (p less than 0.05). Patients with poor overnight metabolic control and raised fasting blood glucose concentrations may benefit from human ultralente insulin, used as part of their twice-daily insulin regimen.

3-Hydroxybutyric Acid↗
PubMed1985

Free insulin levels and metabolic effects of meal-time bolus and square-wave intraperitoneal insulin infusion in insulin-dependent diabetic patients.

The intraperitoneal route may offer more physiological insulin delivery through absorption of a proportion of the dose into the portal circulation. We have compared 1-h square-wave and bolus supplemental infusions of a fixed dose of 10 U of intraperitoneal insulin in 6 C-peptide negative insulin-dependent diabetic patients eating a standard breakfast and compared the insulin, glucose and metabolite responses with those of non-diabetic control subjects. Blood glucose profiles were similar on the two experimental days and although the peak glucose levels were not different from normal they were delayed by 30 min (p less than 0.05). Basal free insulin levels were elevated in diabetic patients (square-wave 19.6 +/- 2.3, bolus 18.7 +/- 1.9 mU/l) compared to controls (7.3 +/- 1.0 mU/l, p less than 0.02) and rose more rapidly after bolus injection than infusion. Peak insulin concentration was achieved at 33 +/- 4 min after bolus, 90 +/- 13 min after infusion (p less than 0.02) and 39 +/- 5 min in normal control subjects. The shape of the profile of free insulin concentration was similar after bolus injection and in the controls, but after square-wave infusion the return to baseline was delayed (p less than 0.05). Fasting intermediary metabolite concentrations were normal on both study days in the patients, but serum cortisol levels were significantly elevated and glucagon concentrations low. Metabolite responses to the meal were not significantly different from normal after bolus injection but increases in lactate and glycerol were seen at some time points between 60 and 180 min after infusion. Glucagon levels remained low after square-wave infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Hydroxybutyric Acid↗
PubMed1985

The influence of insulin antibody levels on the plasma profiles and action of subcutaneously injected human and bovine short acting insulins.

The influence of moderate and low insulin antibody levels on insulin absorption and plasma free insulin profiles is uncertain. Two groups of six C-peptide negative diabetic patients, one with low (3.8 +/- 0.8 mu/l) and one with moderate (16.4 +/- 2.0 micrograms/l) serum insulin antibody levels, were studied. Subjects were given 0.3 U/kg neutral human or acid bovine soluble insulin subcutaneously in random order before breakfast on separate days. Moderate antibody levels significantly blunted the rise in plasma free insulin that followed injection of the human and bovine insulins (p less than 0.05). The rise in blood glucose after breakfast was significantly greater in patients with moderate antibody levels (p less than 0.05) and more marked following the bovine than the human insulin (p less than 0.05). Plasma free insulin, blood glucose and 3-hydroxybutyrate profiles suggest that acid bovine soluble insulin has a significantly more protracted action than neutral human insulin.

3-Hydroxybutyric Acid↗
PubMed1985

Measurement of free insulin concentrations: the influence of the timing of extraction of insulin antibodies.

Plasma insulin concentrations of insulin-treated diabetic patients must be measured after removal of insulin antibodies, usually by precipitation with polyethylene glycol (PEG). Details of the procedure vary between laboratories; commonly, frozen plasma is thawed and incubated at 37 degrees C to restore a presumed equilibrium between free and antibody bound insulin before extraction. The present study was designed to investigate methodological factors that could affect the measured free insulin concentration. In normal subjects PEG extraction of globulins did not disturb measurement of insulin concentrations, whether carried out after incubation for 2 h at 37 degrees C, or storage at -20 degrees C, in either order. Freezing or incubation of PEG extracts of plasma from insulin-treated patients also failed to disturb the measured concentrations of free insulin. When plasma from patients was incubated for 2 h after storage, a marked scatter (51-272%) of measured results occurred when compared to bedside extraction. This problem was not overcome by buffering with HEPES or storage at a lower temperature (-40 degrees C). Incubation at 0 degrees C also severely disturbed the apparent concentrations. Incubation of plasma before extraction and freezing also disturbed the measured result, a problem not corrected by maintaining near physiological pH. Total insulin concentrations measured on acid extracts were not disturbed by any of these manoeuvres. The temperature of centrifugation of blood at the time of venepuncture did not influence the result.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide↗