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Biomedical subjects

C Binder

Publications and source records attributed to C Binder.

At least 163 records · Page 9Linked to original sources

Variation in 125I-insulin absorption and blood glucose concentration.

The absorption of monocomponent porcine 125I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily 125I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the 125I-insulin dose. A significant correlation (p less than 0.05) was found between insulin absorption and blood glucose concentration. Insulin absorption rates were relatively high before all hypoglycaemic episodes and reactive hyperglycaemia was only observed when relatively low insulin absorption rates followed the hypoglycaemic attack. The results show that lability in some insulin dependent diabetics is explained by variation in insulin absorption.

Absorption↗

Pancreatic beta cell secretion during oral and intravenous glucose administration.

The contribution of decreased hepatic insulin extraction to the relative hyperinsulinemia after oral glucose load as compared to intravenous glucose load was studied in 6 normal weight male volunteers by means of an analysis of the relationship between peripheral venous concentrations of insulin and C-peptide following similar glycemic stimuli after oral and intravenous glucose administration. The incremental areas under the insulin and C-peptide curves were higher during oral as compared to intravenous glucose administration, 436 (251--762) per cent and 267 (124-378) per cent respectively (mean and range). The ratio between corresponding incremental areas of insulin and C-peptide were 53 (17--103 per cent higher during oral glucose load. These findings suggest that the augmented peripheral insulin levels after oral glucose administration are caused by a combination of increased beta cell secretion and decreased hepatic insulin extraction.

Adult↗

Bone mineral loss in insulin-treated diabetes mellitus: studies on pathogenesis.

To elucidate pathogenetic factors of bone mineral loss in diabetes mellitus, bone mineral content (BMC), glucose and calcium homeostasis were evaluated in a cross-sectionsl study of 215 insulin-treated diabetics. BMC declined 10% during the first 5 years of diabetes. This coincided with cessation of insulin secretion, deterioration of metabolic control and raising urinary calcium excretion rates of calcium and phosphorus. BMC was inversely correlated to fasting blood glucose (P less than 0.02), to glycosuria (P less than 0.02) and to insulin requirement (P less than 0.002), and positively to the glucagon-stimulated serum C-peptide levels (P less than 0.005). Urinary excretion rates of calcium and phosphorus correlated positively with the degree of hyperglycaemia (P less than 0.001) and glycosuria (P less than 0.001). The skeletal calcium loss corresponded to the excess of urinary excretion during the phase of BMC reduction. There was no evidence of secondary hyperparathyroidism. The relationship between bone loss and disturbed glucose homeostasis indicates that diabetic bone loss is secondary to the metabolic abnormalities, possibly acting directly on bone.

Adolescent↗

Diurnal profiles of serum insulin, C-peptide and blood intermediary metabolites in insulin treated diabetics, their relationship to the control of diabetes and the role of endogenous insulin secretion.

The 24-hour profiles of blood metabolites, serum free and total insulin, and C-peptide were measured in 16 insulin dependent diabetics, and then analysed in order to compare the effects of the presence or absence of residual endogenous insulin secretion and the presence of good or bad diabetic control as judged by the levels of blood glucose or total ketone bodies. Retention of endogenous insulin secretion, responsive to meals, and changes in the level of blood glucose and serum free insulin, were detected in nine patients, its presence having important effects in maintaining metabolic regulation closer towards normal. Despite the fact that apparently well controlled diabetics were selected for the study, the diurnal changes of the levels of blood metabolites, serum free and total insulin and their interrelationships were all grossly abnormal. The levels of both the blood total ketone bodies and the blood glucose were found to be a poor guide to the presence or absence of other metabolic abnormalities of diabetes. High levels of blood total ketone bodies appeared to have a protein sparing effect.

Adult↗

Osteopenia in insulin treated diabetes mellitus. Its relation to age at onset, sex and duration of disease.

Bone mineral content was measured by photon absorptiometry in 215 insulin treated diabetic out-patients aged 7--70 years. As bone mass increases until the age of 20--25 years, patients were so selected that all remained within the same phase of bone mineral storage throughout the entire course of their diabetes. Other criteria for exclusion were diseases or drugs interfering with mineral metabolism and previous use of oral antidiabetic agents. As a group the patients demonstrated a bone mineral deficit of 9.8% compared with sex- and age-matched controls (P less than 0.001). Comparison between patients who had developed diabetes before the age of 20 years and after that of 25 years revealed deficits of 14% and 7%, respectively (P less than 0.001). Sex differences were not observed. The initiation of osteopenia seemed to coincide with the onset of clinical diabetes mellitus, and significantly reduced bone mineral content was observed after 2 years of diabetes (P less than 0.001). After 3--5 years the osteopenia appeared to attain a stable level.

Adolescent↗

The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus.

Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these 'CPR-secretors' there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p less than 0.005) and amylase (r = 0.7, p less than 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.

Adolescent↗

A comparison between diabetics receiving a high or low daily insulin dosage.

Two groups of 8 diabetics, similar in many aspects, who required high (greater than or equal to 128 units) or low (less than or equal to 32 units) total daily insulin dosage were compared during a 24 hour period. C-peptide secretion was detected in all but one of the low dose group, but only in two of the high dose group. No significant differences in serum free and total insulin concentrations were detected and the patterns of blood metabolites were also similar, apart from higher blood glycerol concentrations in the low dose group. No significant differences in the binding characteristics of the antiinsulin antibodies were detected.

C-Peptide↗

Kinetics of human connecting peptide in normal and diabetic subjects.

The metabolic clearance rate (MCR) of synthetic human connecting peptide (C-peptide) was measured with a single-dose injection technique in six normal and seven diabetic subjects and with a constant infusion technique in one normal subject. The MCR of C-peptide did not differ in normal subjects (4.4 ml/min per kg; range, 3.7-4.9) and in diabetic subjects (4.7 ml/min per kg; range, 3.7-5.8). Employment of both techniques in one subject gave similar MCR. The average half-life of C-peptide in plasma calculated from the last 1-h period of the single-dose injection studies was longer in the insulin-dependent diabetics (42.5 min; range, 39.4-48.5) than in the normal subjects (33.5 min; range, 24.9-45.3). These results indicate that the beta-cell secretory capacity of normal and insulin-dependent diabetic subjects can be compared by measuring the C-peptide concentration in peripheral venous plasma. The difference in the half-life of C-peptide in plasma between diabetics and normals suggests an altered kinetics of the disappearance of the peptide, while the overall metabolism, as expressed by the MCR, is similar.

Adult↗

HLA antigens in a family with maturity-onset type diabetes mellitus.

In a family with maturity-onset type of diabetes mellitus inherited as a dominant, autosomal trait (MODY), the HLA genotypes were compared with the glucose tolerance and the plasma insulin response to oral glucose. In the members with impaired glucose tolerance, the plasma insulin response was of the insulino-tardic type, while those with normal or borderline glucose tolerance had a normal plasma insulin response. HLA tissue typing for A, B, C and D series antigens carried out in 19 of the members showed no association between specific HLA antigens and imparied glucose tolerance. Moreover, when analysing the segregation of the disease and the HLA characters, several recombinants between MODY and HLA would have to be postulated if the gene(s) for this form of diabetes mellitus should be closely linked to the HLA locus.

Adolescent↗

Characterization of seven C-peptide antisera.

The plasma C-peptide immunoreactivity (CPR) in 10 normal subjects varied considerably when measured with different antisera in parallel assays. The CPR level correlated with the blank "CPR" value measured in plasma devoid of C-peptide and to a lesser degree with the sensitivity of the standard curves obtained with the individual antisera. Storage of plasma samples at different temperatures and for different lengths of time before the analyses were carried out resulted in further variation in the CPR results. This was caused by a time- and temperature-dependent fall in CPR, which was more pronounced with some antisera than with others. This sensitivity to storage of plasma did not correlate with the antigenic characteristics of the antisera as determined by their reactivity with 11 specific fragments of the C-peptide molecule. The contribution of human proinsulin to the CPR concentration relative in normal subjects was considered to be negligible even though the relative immunoreactivity of human proinsulin and C-peptide ranged from 11 to 143 per cent among these antisera. These results suggest that differences in C-peptide antisera are a major reason for the variation in the concentration of circulating CPR as measured in different C-peptide immunoassays.

Animals↗

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↗

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↗

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↗

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↗

Hypomagnesemia, a risk factor in diabetic retinopathy.

The serum magnesium concentration was measured in 71 insulin-treated diabetic outpatients who had had the disease for 10 to 20 years. The patients were divided into two subgroups according to the severity of their retinopathy. As a whole the patients exhibited a definite hypomagnesemia (P less than 0.001) that was most pronounced in the subgroup having the severest degree of retinopathy (P less than 0.01). The subgroups were comparable regarding known risk factors implicated in diabetic retinopathy. Thus, hypomagnesemia appears to be an additional risk factor in the development and progress of this complication.

Adolescent↗

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↗