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Biomedical subjects

C Binder

Publications and source records attributed to C Binder.

At least 145 records · Page 8Linked to original sources

Continuous subcutaneous insulin infusion: comparison of plasma insulin profiles after infusion or bolus injection of the mealtime dose.

To help optimize meal-time blood glucose control in diabetic patients by continuous subcutaneous insulin infusion we have studied plasma insulin profiles in six normal subjects, suppressing endogenous insulin secretion with somatostatin. Insulin was administered subcutaneously either as a bolus or by high-rate infusion. Mean infusion profiles were similar on the two occasions, with peak levels at 75 and 90 min respectively, and a linear decline to 34% and 36% of peak concentrations at 5 h. Bolus injection resulted in a faster rise in insulin concentration, more consistent with physiological requirements. It is concluded that bolus delivery would be similar in effect while mechanically simpler to achieve than infusion, when part of a dual rate subcutaneous infusion system. The dose should be given 30 min before meals, if peak insulin concentrations are to be coincident with those found physiologically. Insulin concentrations remain high in the post-absorptive phase.

Adult↗

Practical clinical value of the C-peptide response to glucagon stimulation in the choice of treatment in diabetes mellitus.

In order to discriminate between insulin-dependent and non-insulin-dependent patients, serum C-peptide concentration was determined using antiserum M1230 in the fasting state and 6 min after an i.v. injection of 1 mg glucagon in 215 patients treated with insulin and 53 treated with diet and oral antidiabetics. A patient was considered well controlled without insulin when fasting blood glucose was below 8 mmol/l and when glucosuria was absent. After re-evaluation of therapy in hospital it was found that the majority of patients with a post-stimulatory serum C-peptide concentration above 0.60 pmol/ml appeared to have non-insulin-dependent diabetes mellitus. When fasting C-peptide was used, a great overlap was found between the two treatment groups. During evaluation of therapy in hospital, 6 previously insulin-treated patients could be well treated with diet and tablets and 6 diet- and tablet-treated patients required insulin. The glucagon test seems to be of value in the outpatient clinic to discriminate non-insulin-dependent from insulin-dependent patients.

Adult↗

Very early changes in circulating T3 and rT3 during development of metabolic derangement in diabetic patients.

Alterations in circulating iodothyronines were studied in 15 juvenile type diabetic patients during the development of metabolic derangement after withdrawal of insulin. By means of measurements of circulating C peptide, one group of patients with and one without residual beta-cell function had been selected. In both groups there was a gradual decrease in serum T3 during the 12-hour period studied after withdrawal of insulin, while an increase in serum rT3 was observed after 4-6 hours. The alterations in serum T3 and the metabolic derangement were significantly more pronounced in patients without than with residual beta-cell function.

C-Peptide↗

Development of bone mineral loss in insulin-treated diabetes: a 1 1/2 years follow-up study in sixty patients.

The change in bone mass during 1 1/2 years was determined in a longitudinal study of sixty adult insulin-treated diabetic out-patients. During the study period the mean bone mass decreased by 1.30 +/- 0.28 (SEM)% (P less than 0.001), to a mean value of 91.0 +/- 1.7% of normal (P less than 0.001). The rate of bone loss was significantly higher in patients with 1-6 years of diabetes (n = 29, bone loss: 1.96 +/- 0.32%/1 1/2 years) than in patients with longer duration of the disease (n = 31, bone loss: 0.61 +/- 0.44%/1 1/2 years, P less than 0.02). The endogenous insulin secretion estimated with the glucagon-stimulated serum C-peptide concentration decreased during the observation period in 58.6% of the patients with 1-6 years of diabetes compared to 16.1% among patients with 7-11 years of diabetes (P less than 0.002). The rate of bone mineral loss was almost 3 times higher in the twenty-two patients in whom endogenous insulin secretion had deteriorated (2.12 +/- 0.30%/1 1/2 years) than in the thirty-eight patients without as well as with unchanged or increased insulin secretion (0.78 +/- 0.39%/1 1/2 years, P less than 0.01). In twenty patients with an increased insulin dose during the study period the mean bone mineral loss was 2.05 +/- 0.36%/1 1/2 years compared to a mean bone mineral loss of 0.91 +/- 0.38%/1 1/2 years in the forty patients with unchanged or decreased insulin dosage (P less than 0.05). This longitudinal study further supports the hypothesis that the bone mineral loss in insulin-treated diabetic patients begins with the onset of clinical diabetes and that its development is associated with the deterioration of the beta-cell function and with the increment in insulin dosage. The rate of bone mineral loss is high during the first few years of clinical diabetes, but levels off with increasing duration of the disease.

Adult↗

Decreased insulin removal contributes to hyperinsulinemia in obesity.

Peripheral plasma insulin and C-peptide concentrations during oral glucose tolerance tests were measured in 7 severely obese and 12 normal weight nondiabetic subjects. The insulin and C-peptide levels as well as incremental areas under the plasma curves were 2--5 times higher in the obese subjects (P less than 0.05). The C-peptide to insulin molar ratios as well as the relation between incremental areas under the plasma curves of the two peptides were used as relative measures of the hepatic insulin extraction. They were both reduced in the obese subjects, which suggests that decreased insulin removal may contribute to the hyperinsulinemia of obesity. Sixty minutes after the oral glucose load, all of the obese patients had higher peripheral venous insulin concentrations compared with those found in normal subjects with similar C-peptide levels. This suggests that the reduced insulin extraction is not entirely explained by increased beta-cell secretory activity, but is also a specific consequence of obesity.

Blood Glucose↗

Sensitivity of insulin secretion to feedback inhibition by hyperinsulinaemia.

The ability of insulin to inhibit its own secretion was examined in 15 normal subjects given an intravenous infusion of insulin in a dose of 0.25, 0.50, 1.0, 5.0 or 10.0 mU/kg/min for two hours. Arterial plasma insulin concentration achieved during the infusion segregated into three levels of hyperinsulinaemia: 35 +/- 1 (mean +/- SEM), 87 +/- 15 and 828 +/- 210 muU/ml. Plasma glucose concentration was kept constant at the basal level by a variable glucose infusion. Fasting C-peptide (0.29 +/- 0.02 pmol/ml) fell significantly in all subjects during hyperinsulinaemia and reached a concentration of 0.19 +/- 0.03 pmol/ml at 60 min and 0.14 +/- 0.03 at 120 min after the start of the insulin infusion. The C-peptide response was not related to the infusion dose nor to the steady state plasma insulin concentration. It is concluded that (a) basal insulin secretion as evaluated from C-peptide measurements is inhibited by small (24 +/- 3 muU/ml) physiological elevations in plasma insulin concentration independent of changes in plasma glucose, and (b) supraphysiological or even pharmacological elevations in plasma insulin do not result in a further decrease in endogenous insulin secretion above that achieved with mild hyperinsulinaemia.

Adult↗

Islet-cell antibodies and beta-cell function in insulin-dependent diabetics.

Residual insulin secretion and islet-cell antibodies were studied in 399 insulin-dependent diabetics with age at onset of between 10--19.9 years (248 patients) or 30--39.9 years (151 patients). We found the prevalence of islet-cell antibodies to be independent of residual beta-cell function as measured by serum C-peptide and age at onset. The cause and role of the persistence of islet-cell antibodies in insulin-dependent diabetics remain obscure.

Adolescent↗

Importance of insulin absorption, subcutaneous blood flow, and residual beta-cell function in insulin therapy.

The interaction between variation in insulin absorption and beta-cell function was studied as well as the possible relation between subcutaneous blood flow through the region of injection and the variability in insulin absorption. The results indicate that the dose of insulin, the type of insulin preparation and the local blood flow influence the insulin absorption. Residual endogenous insulin secretion, governed by the blood glucose values, serves as a modulator.

Adult↗

Beta-cell function and metabolic control in insulin treated diabetics.

In a random one day study beta-cell function was evaluated in 210 insulin treated diabetics by the serum C-peptide concentration 6 min after iv injection of 1 mg of glucagon. Sixty-five patients (31%) had residual beta-cell function. As a group these patients were characterized by having a higher age at onset of diabetes (P less than 0.01), a shorter duration of disease (P less than 0.01) and by receiving a smaller dose of insulin (P less than 0.01). However, their quality of metabolic control did not differ from the patients without beta-cell function. Although the concentrations of post-stimulatory C-peptide correlated inversely with both the 24-hour glycosuria (P less than 0.01) and the fasting blood glucose concentrations (P less than 0.02), only a subgroup with C-peptide concentrations exceeding 0.30 pmol/ml showed a definitely better degree of metabolic control than those without beta-cell function. As this subgroup also received the smallest dose of insulin these observations suggest that maintenance of beta-cell function above this level facilitates good metabolic control. Evidence is presented suggesting that measurements of the 24-hour glycosuria undertaken in a diabetes clinic create a too optimistic impression of the quality of metabolic control during every day life.

Adolescent↗

Insulin secretory reserve in insulin dependent patients at time of diagnosis and the first 180 days of insulin treatment.

Eleven newly diagnosed insulin dependent patients were studied before and during the first 16 h after start of insulin treatment. All the patients were found to have significant amounts of C-peptide in plasma indicating residual insulin secretion. The fall in blood glucose after start of insulin therapy was followed by a parallel decrease in C-peptide (R = 0.99, P < 0.01) suggesting that the beta-cells may respond to variation in blood glucose. Eight of the patients were studied 1, 4, 7, 14, 90 and 180 days after start of insulin therapy. During the first 90 days of treatment an increasing maximal C-peptide concentration was found after a standard breakfast test meal. Two thirds of this improvement i beta-cell function was found after the initial 14 days with an average increase in maximal C-peptide of 260 per cent. The sensitivity to glucose improved.

Adolescent↗

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↗

C-peptide response to glucagon in diabetics with and without complications.

Beta cell function has been studied by measurement of C-peptide responses to intravenous glucagon in 11 diabetics with advanced complications and compared with nine long-term diabetics without complications. The majority had no C-peptide responses, but there was evidence of beta cell function in one patient from each group. These observations suggest that some factor other than continuing beta cell function is involved in the complications of insulin-requiring diabetics.

Adult↗

Lipid metabolites and nitrogen balance after abdominal surgery in man.

The relation of lipid metabolism to nitrogen balance was studied in patients having undergone abdominal surgery and was compared with control subjects who had fasted for a similar period. The patients had lower circulating concentrations of glycerol, non-esterified fatty acids and ketone bodies. There were inverse correlations between blood alanine and ketone body concentrations in both patients (r = -0.64, P less than 0.01) and controls (r = -0.58, P less than 0.01). Nitrogen excretion by patients (12.7 mmol/kg body weight/day +/- 1.4 s.e. mean) was greater than by controls (9.2 mmol kg(-1)d(-1) +/- 0.8, P less than 0.05), but a more marked difference was noted for urinary methyl histidine excretion of 5.1 +/- 0.5 mmumol kg(-1) d(-1) by patients and only 2.5 +/- 0.3 mumol kg(-1) d(-1) by controls (P less than 0.01), a disparity indicative of more active protein turnover after surgery.

Abdomen↗

Bone loss in diabetes: effects of metabolic state.

The significance of different risk factors for the development of bone loss in diabetes mellitus was evaluated in a cross sectional study of 215 insulin treated diabetic outpatients. Bone mineral content in the forearms was measured by photon absorptiometry and the metabolic status was evaluated by three indices: residual B-cell function, insulin dosage and fasting blood glucose. The mean bone mineral content was reduced to 90.2% of sex- and age-matched normal mean values (P less than 0.001). Stratification of the patients showed that bone mineral content was 99.3% of that found in sex- and age matched normal subjects in the group with residual B-cell function, low insulin dosage and low fasting blood glucose; it was only 79.3% of normal in the group with no detectable insulin secretion, high insulin dosage and more severe hyperglycaemia. Thus, residual insulin secretion and the quality of metabolic control are major factors in determining bone mineral content in insulin treated diabetic patients.

Blood Glucose↗