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Biomedical subjects

I Hanning

Publications and source records attributed to I Hanning.

32 records · Page 2Linked to original sources
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↗
PubMed1985

The effect of mixing human soluble and human crystalline zinc-suspension insulin: plasma insulin and blood glucose profiles after subcutaneous injection.

The effect of mixing human soluble insulin with two newly developed formulations of human crystalline zinc-suspension insulin was studied in two groups of 8 normal and 6 diabetic subjects. Mixing Human Actrapid with Human Ultratard and Humulin-S with Humulin-Zn, for 60 s before subcutaneous injection, significantly blunted the rise in free insulin levels (p less than 0.05) and the onset of action of the short-acting insulins (p less than 0.01). The loss of solubility that occurs on mixing these insulins, with the consequent loss of the rapid acting component, may diminish their therapeutic usefulness in the control of post-prandial blood glucose.

Adult↗
PubMed1985

A comparison of 3 methods for assessing insulin sensitivity in subjects with normal and abnormal glucose tolerance.

The euglycaemic clamp, insulin sensitivity test with somatostatin, and insulin sensitivity test without somatostatin, were compared as in vivo methods of assessing insulin sensitivity. Fifteen subjects with varying degrees of glucose tolerance were studied. Somatostatin was not found to influence the assessment of insulin sensitivity by the insulin sensitivity test. When glucose disposal was expressed as metabolic clearance rate significant strong correlations were found between the euglycaemic clamp technique and the insulin sensitivity test with (r = 0.90) and without (r = 0.83) somatostatin. The effects of the tests on intermediary metabolism were also similar, and all 3 tests showed a similar impairment of insulin sensitivity in subjects with abnormal glucose tolerance. The insulin sensitivity test without somatostatin thus provides a simple and economical tool for studying insulin sensitivity.

Adult↗
PubMed1984

A comparison of the artificial pancreas (glucose controlled insulin infusion system) and a manual technique for assessing insulin sensitivity during euglycaemic clamping.

Two main methods are available for assessing insulin sensitivity with the hyperinsulinaemic euglycaemic clamp technique: one employs a glucose-controlled insulin infusion system (the Biostator) with automatic feedback control; the second depends on frequent glucose measurement and the use of an algorithm and a pocket calculator ('manual') to determine the glucose infusion rate. The amount of glucose infused is a measure of insulin sensitivity. The efficiency of the two methods was compared in nine normal subjects (seven lean, two obese). After an overnight fast subjects were infused with insulin at 50 mU X kg-1 X h-1 for 2 h; this rate was doubled during the first 10 min for the manual technique. Blood glucose averaged 4.7 +/- 0.1 and 4.8 +/- 0.1 mmol/l from 0 to 120 min for Biostator and manual techniques and did not deviate significantly from the desired level. Variability of the clamp was also similar over the same period (coefficient of variation 5.1 +/- 0.6% and 6.4 +/- 0.7%, Biostator and manual). Glucose infused to maintain steady state from 60 to 120 min was higher, however, with the manual than the Biostator method (5.7 +/- 0.6 versus 4.4 +/- 0.6 mg X kg-1 X min-1, p less than 0.01) even when the loading dose was omitted, although the two methods correlated closely (p less than 0.05). Glucose infusion rate varied more from minute to minute with the Biostator (coefficient of variation 28.8 +/- 3% versus 12.2 +/- 2.1%). Steady-state serum insulin levels (30-120 min) were the same during both methods.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1984

Factors governing the human immune response to injected insulin.

Seventy-nine patients were observed prospectively during their initial period of treatment with conventional bovine insulins. Insulin antibody levels 6 months after starting insulin therapy did not correlate with age, gender or beta cell function at onset of treatment. Patients who required soluble insulin in addition to isophane insulin developed higher levels of insulin antibody. Patients bearing the HLA-B8, DR3 and C4AQO alleles had lower levels of insulin antibody, whereas those bearing DR7 produced significantly higher levels. Other alleles at the C4A, C4B, C2, factor B or Gm loci did not appear to have a significant effect on insulin antibody production. The hyporesponsiveness of B8/DR3/ C4AQO -positive individuals probably reflects a non-specific abnormality of immunity whereas the enhanced responsiveness of those positive for DR7 suggests the presence of a specific immune response gene for insulin.

Adolescent↗
PubMed1984

The mechanism of action of guar gum in improving glucose tolerance in man.

Experiments were carried out in human volunteers to investigate the mechanism by which guar gum improves glucose tolerance. Guar reduced both plasma glucose and insulin responses to an oral glucose load, and delayed gastric emptying. However, there was no correlation between changes in individual blood glucose responses and changes in gastric emptying rates induced by guar. With a steady-state perfusion technique, glucose absorption was found to be significantly reduced during perfusion of the jejunum with solutions containing guar, but returned to control values during subsequent guar-free perfusions. Preperfusing the intestine with guar did not affect electrical measurements of unstirred layer thickness in the human jejunum in vivo. Experiments in vitro established that glucose diffusion out of a guar/glucose mixture was delayed under conditions of constant stirring. We conclude that guar improves glucose tolerance predominantly by reducing glucose absorption in the small intestine. It probably does this by inhibiting the effects of intestinal motility on fluid convection.

Adolescent↗
PubMed1984

Continuous intraperitoneal insulin infusion in the management of severely brittle diabetes--a metabolic and clinical comparison with intravenous infusion.

We report a comparison of continuous intraperitoneal insulin infusion (CIPII) and continuous intravenous insulin infusion (CIVII) in 6 diabetic patients in whom severe hyperglycaemia and ketoacidosis could not be prevented with subcutaneous or intramuscular insulin. In the short term both methods were equally effective in maintaining glycaemic control. Blood glucose, glycerol, and 3-hydroxybutyrate levels were normal but lactate and pyruvate levels remained elevated with both treatments. Insulin requirements were significantly lower on CIPII than CIVII (70 vs 113 U/day, p less than 0.01). Intraperitoneal insulin delivery was associated with near physiological peripheral plasma insulin profiles in 3 patients. In the longer term CIVII was associated with frequent septicaemia and thrombosis, and was successful in preventing hospitalization for 6 months or more in only one patient. Despite technical problems with CIPII complications were less serious and hospital admission due to metabolic decompensation was prevented for 6 months or more in 3 patients. When subcutaneous insulin delivery is unsuccessful in the management of brittle diabetes, CIPII should be considered rather than CIVII because it is more likely to be successful and less likely to cause serious complications.

Adolescent↗
PubMed1984

A comparison of the effects of semisynthetic human insulin and porcine insulin on transmembrane ion shifts and glucose metabolism during euglycaemic clamping.

Disturbances of potassium, calcium, phosphate and magnesium homeostasis in diabetes mellitus are well documented. We have compared the effects of semisynthetic human and pancreatic porcine insulin on transmembrane shifts of these ions, and on glucose metabolism, at two insulin infusion rates, 20 and 50 mU/kg/h, during euglycaemic clamping for 2 h in 6 normal volunteers. The glucose requirements and the changes in blood metabolite concentrations were not significantly different during the porcine and human insulin infusions. Serum potassium levels, however, showed a significant greater decline with infusions of porcine insulin (4.2 +/- 0.1 to 3.5 +/- 0.1 mmol/l) compared with human insulin (4.2 +/- 0.1 to 3.7 +/- 0.1 mmol/l) at 50 mU/kg/h (P less than 0.05). Potassium levels were significantly lower during the porcine insulin infusion at 105 and 120 min and at 15 and 30 min after stopping the infusion. Electrocardiographic T-wave voltage decreased during the porcine and human insulin infusion by 0.13 +/- 0.02 and 0.10 +/- 0.01 mV, respectively (P less than 0.02). Changes in serum levels of magnesium, calcium, phosphate, and red blood cell concentrations of magnesium and 2,3-DPG, were not significantly different between the insulins. Thus a small but significant greater decline in potassium levels with similar glucose requirements was found during iv administration of porcine insulin compared with human insulin.

Animals↗
PubMed1983

Intermediate acting insulin given at bedtime: effect on blood glucose concentrations before and after breakfast.

Six C-peptide deficient diabetics receiving twice daily mixtures of short and intermediate acting insulins were selected for study because of persistently raised blood glucose concentrations before and after breakfast. They were investigated to assess the effect of moving their evening injection of intermediate acting insulin to bedtime. The patients' usual twice daily insulin treatment was optimised and compared with the bedtime regimen during inpatient metabolic studies and an outpatient crossover study. With the conventional injection regimen blood glucose concentration rose sharply from 0500 to reach a fasting mean value of 10 +/- SE 1 . 6 mmol/l (180 +/- 29 mg/100 ml) and 16 . 8 +/- 2 . 2 mmol/l (303 +/- 40 mg/100 ml) after breakfast. By contrast, when the evening dose of intermediate acting insulin was delayed until bedtime the nocturnal rise in blood glucose concentration started later and was significantly lower both fasting (7 . 5 +/- 1 . 1 mmol/l (135 +/- 20 mg/100 ml); p less than 0 . 02) and after breakfast (13 . 2 +/- 1 . 4 mmol/l(238 +/- 25 mg/100 ml); p less than 0 . 02). Fasting blood concentrations of ketone bodies (3-hydroxybutyrate) were also significantly decreased. Plasma free insulin concentrations showed the predicted changes in five of the six patients. Blood glucose profiles collected over four months during the outpatient study confirmed the beneficial effect of giving intermediate acting insulin at bedtime.

Adult↗
PubMed1983

Insulin sensitivity in hyperthyroidism: measurement by the glucose clamp technique.

Sensitivity to porcine insulin has been compared in overnight fasted hyperthyroid and control subjects using a euglycaemic clamp technique. Basal values for blood glucose, lactate, pyruvate, alanine, serum insulin and C-peptide were similar in the two groups, whilst blood glycerol (hyperthyroid 0.11 +/- 0.02 (mean +/- S.E.) vs. control 0.06 +/- 0.01 mmol/l, P less than 0.01) and blood 3-hydroxybutyrate (0.28 [0.03-0.79, range ]vs 0.09 [0.01-0.29 ]mmol/l, P less than 0.05) were increased in hyperthyroidism. During the 2 hour insulin infusion (0.05 U/kg/h), serum insulin plateaued at the same level (44 +/- 4 vs 44 +/- 1 mU/l) and insulin metabolic clearance rates were similar (1.21 +/- 0.10 vs 1.25 +/- 0.03 l/min). Serum C-peptide levels also decreased by similar amounts (40 +/- 8 vs 47 +/- 6%). The amount of glucose infused to maintain euglycaemia was identical during the second hour of insulin infusion (290 +/- 50 vs 330 +/- 30 mg/kg) as were the increments in lactate and pyruvate concentrations. Blood glycerol values decreased in both groups although values in hyperthyroid patients remained significantly higher than in controls. 3-Hydroxybutyrate concentrations fell to similar values in the two groups. These findings suggest that insulin-stimulated glucose metabolism and inhibition of ketogenesis are normal in hyperthyroidism.

3-Hydroxybutyric Acid↗
PubMed1982

A comparison of the activity and disposal of semi-synthetic human insulin and porcine insulin in normal man by the glucose clamp technique.

The activity of semi-synthetic human insulin has been compared with porcine insulin in normal man using an euglycaemic glucose clamp at two different insulin infusion rates. In the two hour infusion insulin levels plateaued for both types of insulin at 44-48 mU/l (infusion rate 0.05 U kg body weight-1 h-1) and 22-24 mU/1 (0.02 U kg-1 h-1), giving identical metabolic clearance rates. The glucose delivery required to maintain euglycaemia in the second hour of insulin infusion was 13.9 +/- 2.1 g (mean +/- SEM) and 14.7 +/- 1.5 g (NS) at the lower dose for porcine and human insulins respectively, and 27.1 +/- 2.5 and 28.0 +/- 2.9 g (NS) at the higher dose. The potency ratio for human, compared with porcine, insulin was 1.06 +/- 0.12. No differences were seen in the time of onset of action of the insulins, serum half-life or distribution space. The responses of blood lactate, pyruvate, alanine, glycerol and 3-hydroxybutyrate were identical. No untoward reactions occurred. The activity and disposal of this semi-synthetic human insulin are indistinguishable from porcine insulin in normal euglycaemic man.

Adult↗
PubMedDate not supplied

The oral glucose tolerance test (OGTT): effect of rate of ingestion of carbohydrate and different carbohydrate preparations.

The glucose load of the oral glucose tolerance test (OGTT) is well standardized. However, recommendations on rate of ingestion and nature of the load are vague. In this study the effect on blood glucose, serum insulin, C-peptide, and plasma gastric inhibitory polypeptide (GIP) of giving 75 g glucose in 300 ml over 1 and 10 min (G1 and G10) was investigated in six subjects. In five an isocaloric amount of partially hydrolyzed starch (Hycal) was also used (H1 and H10). The fast glucose intake, compared with the slow ingestion, resulted in an earlier rise in blood glucose levels, accompanied by a faster serum insulin and C-peptide response. Between 90 and 135 min blood glucose concentrations were significantly higher after the 10-min glucose intake. At 120 min blood glucose levels were 5.5 +/- 0.5 and 4.7 +/- 0.5 mmol/L, respectively, for G10 and G1 (P less than 0.05). In the first half hour after slow and fast Hycal intake no differences were seen in blood glucose, serum insulin, and C-peptide levels. Between 45 and 120 min blood glucose levels were significantly higher after the 10-min Hycal intake. At 120 min blood glucose levels were 5.3 +/- 0.2 and 4.4 +/- 0.1 mmol/L, respectively, for H10 and H1 (P less than 0.01). Except for a faster rise in glucose and insulin levels after glucose loading in 1 min, no further differences were found, when compared with Hycal. No significant differences were seen in the GIP responses. Thus differences in rates of ingestion can cause significant differences in later results. A standard time for glucose ingestion should be specified.

Adult↗
PubMedDate not supplied

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↗