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Biomedical subjects

O K Faber

Publications and source records attributed to O K Faber.

At least 73 records · Page 4Linked to original sources
PubMed1978

Heterogeneity of circulating human C-peptide.

Values reported for serum C-peptide immunoreactivity in healthy individuals vary considerably. To assess factors that contribute to this finding, three human C-peptide assay systems were developed utilizing three distinct antisera that react differently with various C-peptide fragments. Preparations of natural pancreatic and synthetic human C-peptide standards were compared immunologically in these systems. The curves of the natural C-peptide and the synthetic preparations were not identical. The relative immunoreactivity of each standard varied, depending on the particular antiserum used. Serum C-peptide concentrations varied when measured in the different assay systems. Furthermore, the results of dilution and recovery tests and stability of the C-peptide during storage showed differences among the three assays. Gel filtration of serum indicated heterogeneity within the major C-peptide peak, and in addition, a smaller peak of lower molecular weight material was present in some samples. Although degradation of serum C-peptide may occur during storage, fragments of C-peptide may also be secreted or arise during in-vivo metabolism. Thus, the present studies indicate the need for careful standardization and checking of each particular assay system before its use in clinical studies.

C-Peptide↗
PubMed1978

Kinetics of human C-peptide in man.

A review of studies concerned with the metabolism of human C-peptide showed that the kidney is the major organ in C-peptide removal. The turnover rate of C-peptide was similar to that of proinsulin but considerably slower than that of insulin. An analysis of corresponding C-peptide and insulin concentrations in normal subjects after the administration of oral glucose or intravenous glucagon was used to define the relationships between the two peptides. These results show that different peripheral vein concentrations of insulin may correspond to identical C-peptide concentrations, depending on sampling conditions.

C-Peptide↗
PubMed1978

Residual beta-cell function and its metabolic consequences.

Improvement in the sensitivity and specificity of the C-peptide immunoassay and studies of larger groups of patients have increased our knowledge of the importance of residual beta-cell function and its metabolic consequences in insulin-treated diabetic patients. During the first five to 10 years after the onset of diabetes mellitus residual beta-cell function is demonstrable in the majority of insulin-treated patients irrespective of the severity of the initial symptoms and only partly dependent on the patient's age at diagnosis. Residual beta-cell function facilitates good control. Stable patients have a higher C-peptide concentration in plasma than unstable ones, but unmeasurable C-peptide is not always associated with poor control. More data are needed before the full significance of an even minimal reserve of beta-cell function is elucidated. It also remains to be shown whether the reductive in beta-cell function in diabetic patients has a qualitative as well as quantitative component.

C-Peptide↗
PubMed1978

Prevalence of residual beta-cell function in insulin-dependent diabetics in relation to age at onset and duration of diabetes.

The influence of the age at onset as well as the duration of disease on the prevalence of residual beta-cell function was studied in insulin-dependent diabetic patients. Two hundred and sixty-seven patients presented at an early age (10-19.9 years) and 158 patients had a late onset (30-39.9 years of age). beta-cell function was evaluated by measuring serum C-peptide immunoreactivity. Fifty-six patients (21.0 per cent) in the early-onset group and 64 (40.5 per cent) in the late-onset group had residual beta-cell function. The prevalence of residual beta-cell function was almost 100 per cent during the first two years of disease and was lower thereafter in diabetics with early onset. About 15 per cent of all patients with a duration between 15 and 35 years had residual beta-cell secretory function.

Adolescent↗
PubMed1978

Plasma C-peptide in uraemic patients.

The kidney has been suggested as the main organ for the degradation of C-peptide. This hypothesis was tested in subjects with normal fasting blood glucose concentration and varying degrees of renal failure. Forty-nine subjects with endogenous creatinine clearance ranging from 0--25 ml/min were studied. The basal steady state concentrations of C-peptide (CP) and the immunoreactivity of insulin (IRI) were determined in plasma from fasting patients. The average IRI was similar to that found in normal subjects while a higher CP was found in all patients but two. The average CP in the nephrectomized patients was six times higher than the mean CP in normal subjects (0.35 pmol/ml). There was a significant inverse correlation between clearance and CP (r = 0.51, P less than 0.001) with the highest CP in nephrectomized patients. It is concluded that the increased CP in renal failure, and especially the markedly increased CP in the nephrectomized group supports the hypothesis of the kidney being the organ mainly responsible for the degradation of C-peptide also in man.

Adult↗
PubMed1977

Hyperinsulinism of hepatic cirrhosis: Diminished degradation or hypersecretion?

The breakdown of proinsulin in the pancreatic beta cell yields insulin and C-peptide which are secreted in equimolar amounts. Unlike insulin, C-peptide is not degraded significantly by the liver, so that its measurement should give a better assessment of insulin secretion than estimation of peripheral insulin levels alone; particularly in the presence of hepatic dysfunction. Plasma C-peptide and insulin response to an oral glucose load have therefore been assessed in 14 cirrhotic and 7 normal subjects. Cirrhotic patients were divided into hyperinsulinaemic and normoinsulinaemic groups based on fasting plasma-insulin concentrations. Fasting blood-blucose and plasma-C-peptide concentrations were the same in normal and cirrhotic subjects, suggesting that basal pancreatic insulin secretion was the same in all subjects. Thus the C-peptide/insulin ratio was significantly decreased in hyperinsulinaemic subjects (2-13 +/- 0-31, compared with 4-63 +/- 0-48 in controls). After oral glucose, the two groups of cirrhotic patients showed the same glucose intolerance. C-peptide concentrations were also the same but insulin concentrations were markedly increased in the hyperinsulinaemic group. It is suggested that pancreatic insulin secretion is not increased in cirrhosis and that the peripheral hyperinsulinism is due solely to decreased hepatic insulin degradation secondary to either spontaneous portal-systemic shunting or to parenchymal damage.

Administration, Oral↗
PubMed1977

B-cell function and blood glucose control in insulin dependent diabetics within the first month of insulin treatment.

Seventeen insulin dependent diabetics were studied after two to four weeks of insulin treatment in a situation approximating to their normal daily life. Some endogenous insulin secretion, assessed by plasma C-peptide determinations, was present in all. Plasma C-peptide concentration was positively correlated with the blood glucose concentration and increased after breakfast, lunch and dinner (p less than 0.01); both peak values and relative increases were lower than those observed in normal subjects (p less than 0.01). The highest insulin secretory capacity was found in subjects with the least unstable blood glucose concentration (r=0.57, p less than 0.03), and these patients required the smallest insulin doses (r=0.54, P less than 0.04). These findings demonstrate the metabolic importance of a preserved B-cell function.

Adolescent↗
PubMed1977

Prevalence of residual B-cell function in insulin-treated diabetics evaluated by the plasma C-etide response to intravenous glucagon.

In 83 insulin-treated diabetics the influence of the duration of insulin treatment on the prevalence of residual insulin secretion was examined by determining the plasma C-peptide concentration before and after intravenous injection of 1 mg of glucagon. In 64 patients, plasma C-etide concentration was also determined before and after a standard meal. There was a good correlation between the C-peptide response to glucagon and to the meal (r = 0.67; p less than 0.0001) suggesting that the glucagon test will predict the B-cell response during everyday life. The predictive value of a positive glucagon test was 84% and of a negative test 100%. A preserved, but reduced, B-cell function was demonstrable in 36 of 83 patients. Residual B-cell function was most frequent in the patients with the shortest duration of diabetes. The metabolic importance of endogenous insulin was demonstrated by the significantly lower insulin requirement in the patients with residual B-cell function.

Blood Glucose↗
PubMed1977

Heterogeneity of circulating C-peptide.

Serum C-peptide levels vary when measured with different immunoassay systems. In order to assess the factors contributing to this finding, serum C-peptide was measured in two assays utilizing different antisera, but the same standards and labeled peptide. The antisera were characterized with synthetic C-peptide fragments and their reactivities towards some of these fragments differed. The results of dilution and recovery tests and stability of the C-peptide during storage showed differences between the two assays. Gel filtration experiments indicated heterogeneity within the major C-peptide peak, and, in addition, a smaller peak of lower molecular weight material was present in some sera. Although degradation of serum C-peptide may occur during storage or with freezing and thawing, fragments of C-peptide may also be secreted or arise during in vivo metabolism.

Animals↗
PubMed1977

C-peptide response to glucagon. A test for the residual beta-cell function in diabetes mellitus.

Pancreatic beta-cell secretory activity was measured in 17 patients with insulin-dependent diabetes mellitus of less than 19 months' duration and in 10 nondiabetic subjects by means of the peripheral plasma C-peptide response to 1 mg. of glucagon I.V. The C-peptide response to a meal was also measured in the diabetic patients. Residual beta-cell function was present in all the diabetic patients as indicated by significant amounts of C-peptide in plasma. Significant increases in C-peptide were observed in 16 after glucagon stimulation and in 15 after the meal. Both absolute and relative increase in C-peptide were reduced in the diabetic patients. The increase in C-peptide was correlated to the fasting C-peptide concentration both after glucagon (r=0.86, p less than 0.001) and after the meal (r=0.66, p less than 0.01). The responses to the meal and to glucagon were correlated (r=0.77, p less than 0.005), indicating a high predictive value of the glucagon test as to how the beta-cells will respond during normal daily life.

Adolescent↗
PubMed1976

Production of antisera to synthetic benzyloxycarbonyl-C-peptide of human proinsulin.

Antisera to the C-peptide of human proinsulin were obtained by immunizing guinea pigs with synthetic benzyloxycarbonyl-C-peptide conjugated to human albumin with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide. In three series of 10, the animals were injected with C-peptide conjugated to albumin in the molar ratio of 23 : 1, 15 : 1, and 4 : 1, respectively. Antibodies to human C-peptide were present in all the surviving 25 animals. Fifteen of the antisera were suitable for measuring C-peptide concentrations lower than 0.10 pmol/ml. The antisera demonstrated an increasing immunogenicity with increasing molar ratio of C-peptide to albumin in the conjugate. In the fourth series, ten guinea pigs immunized with benzyloxycarbonyl-C-peptide ionically bound to QAE-Sephadex A-25 did not produce detectable antibodies to C-peptide. A qualitative evaluation of the radioimmunoassay by use of the antiserum with the highest titer and sensitivity, "M 1230", revealed a mean intra-assay and inter-assay coefficient of variance of 3.2 and 9.6%, respectively.

Animals↗
PubMed1975

The effect of chloramphenicol and sulphaphenazole on the biotransformation of cyclophosphamide in man.

1 The metabolism of cyclophosphamide was investigated before and following treatment with chloramphenicol (five subject) and sulphaphenazole (seven subjects). 2 The biotransformation of cyclophosphamide was retarded after chloramphenicol treatment as indicated by prolongation in the mean serum half-life from 7.5 h to 11.5 h combined with decreased peak activity and integrated concentrations of metabolites. 3 In the sulphaphenazole treated subjects the rate of biotransformation of cyclophosphamide was significantly inhibited in two, unaltered in three and enhanced in two. The inconsistency of the results is discussed.

Aged↗
PubMedDate not supplied

Diurnal profiles of intermediary metabolites in insulin-dependent diabetes and their relationship to different degrees of residual B-cell function.

Diurnal profiles of blood metabolites, insulin and C-peptide were measured in 18 insulin dependent diabetics with less than 2-year duration of disease. Seventeen of the 18 patients had endogenous insulin secretion. A significant inverse correlation was found between mean C-peptide and mean blood glucose. Patients with maximal C-peptide equal to or above 0.30 pmol/ml had a better degree of control evaluated from mean blood glucose in spite of being treated with less insulin compared to patients with less B-cell function. The mean concentrations of alanine, lactate, glycerol and beta-hydroxybutyrate were not different in patients with CPR equal to or above 0.30 pmol/ml compared to patients with less CPR. The highest concentration in blood hydroxybutyrate for all the patients was seen in the fasting state, and the disappearance rate of blood hydroxybutyrate after breakfast was inversely correlated with the residual B-cell function. During the study period the mean insulin concentration in the diabetics and the normals was the same, but the brisk increase in insulin concentration related to meals was decreased or lost in the diabetics. Compared to normals the mean blood glucose, beta-hydroxybutyrate and glycerol were higher in the diabetics and the diurnal changes were grossly abnormal. No difference was found in alanine concentration and mean lactate concentration, but the increase in lactate seen after meals in normals was lost in the diabetics. The results confirm that other metabolites than glucose are abnormal in diabetics and that residual B-cell function has metabolic consequences for other metabolites than glucose during daily life conditions.

3-Hydroxybutyric Acid↗