Urinary C-peptide Excretion Research Articles

Effects of Hemipancreatectomy on Insulin Secretion and Glucose Tolerance in Healthy Humans

Pancreatic tissue obtained by hemipancreatectomy from healthy living related donors has been transplanted into recipients with Type I diabetes mellitus. To determine the metabolic consequences of this procedure for the donors, we carried out oral glucose-tolerance testing and 24-hour monitoring of serum glucose levels and urinary C-peptide excretion as a measure of insulin secretion in 28 donors, both before and one year after hemipancreatectomy. The mean fasting serum glucose level was significantly higher one year after the procedure (mean +/- SD, 5.4 +/- 0.9 vs. 4.9 +/- 0.5 mmol per liter; P less than 0.003), as was the serum glucose value two hours after the administration of glucose (8.7 +/- 2.9 vs. 6.5 +/- 1.0 mmol per liter; P less than 0.001). The fasting serum insulin level was significantly lower one year after hemipancreatectomy (33.0 +/- 21.6 vs. 38.4 +/- 21.6 pmol per liter; P less than 0.05), as was the area under the insulin curves during the oral glucose-tolerance test (52,554 +/- 22,320 vs. 76,230 +/- 33,354 pmol per liter per minute; P less than 0.04). The mean 24-hour serum glucose-profile value was higher at one year, and the 24-hour urinary C-peptide excretion was lower in the 17 donors who underwent these studies. Seven of the 28 donors had abnormal glucose tolerance one year after hemipancreatectomy; however, insulin secretion in these 7 donors was indistinguishable from that in the 21 donors who had normal glucose tolerance. All 28 donors had fasting serum glucose concentrations lower than 7.8 mmol per liter, and their mean 24-hour plasma glucose levels remained within the normal range. We conclude that in healthy donors hemipancreatectomy results in a deterioration of insulin secretion and glucose tolerance, as measured one year later. Further study is required to ascertain whether the development of clinical diabetes mellitus is a risk inherent in hemipancreatectomy.

Dietary carbohydrate content determines responsiveness to growth hormone in energy-restricted humans.

To determine if diet composition influences responses to GH, we fed 11 obese women diets containing 12 Cal/kg ideal BW (IBW) for 2 5-week study intervals. Nonprotein calories were supplied to 6 subjects as 72% carbohydrate (high carbohydrate diet), and 5 subjects received 80% of their nonprotein calories as lipid (high lipid diet). Protein intake was constant (1.0 g/kg IBW) in both groups. During 1 study interval we gave injections of GH (0.1 mg/kg IBW) every other day for 3 weeks (weeks 2-4), and in the other interval injections of vehicle were given. Subjects ingesting the high carbohydrate diet excreted significantly less urinary nitrogen [660.2 +/- 124.1 mmol/day (mean +/- SD)] than those who received high lipid (794.2 +/- 198.5 mmol/day; P less than 0.001), and GH injections reduced nitrogen excretion in the high carbohydrate subjects (532.8 +/- 123.8 mmol/day), but not in the high lipid subjects (743.7 +/- 126.6 mmol/day). The subjects receiving the high carbohydrate diet had a significant increase in serum insulin-like growth factor-I (IGF-I; from 36.2 +/- 9.7 to 55.9 +/- 6.6 nmol/L) and urinary C-peptide excretion (from 43.9 +/- 25.6 to 60.8 +/- 29.4 nmol/day) in response to GH. The IGF-I response attenuated slowly over the 3-week treatment interval. On the other hand, the high lipid group had lesser increases in IGF-I (from 31.0 +/- 6.5 to 41.7 +/- 8.8 nmol/L) and C-peptide excretion (from 24.3 +/- 28.9 to 29.8 +/- 32.8 nmol/day), and IGF-I concentrations declined to control values after only 5 days of GH injection. We believe that this initial IGF-I response was due to an antecedent 35-Cal balanced diet. The mean increment in serum FFA 4 h after GH injection was significantly less in subjects fed the high lipid diet (0.53 +/- 0.40 meq/L) than in those fed the high carbohydrate diet (0.83 +/- 0.43 meq/L). GH injections produced more body fat loss than injections of vehicle whether expressed as percent body fat lost (GH, 3.7 +/- 1.0%; vehicle, 2.8 +/- 0.7%, P less than 0.05) or as the fraction of weight lost as fat (fat loss/weight loss; GH, 0.81 +/- 0.13; vehicle, 0.64 +/- 0.08; P less than 0.005). There was an inverse correlation between the percentage of body fat lost and mean urinary C-peptide excretion during GH injections (r = -0.70; P less than 0.05), suggesting that stimulation of insulin secretion by GH might antagonize the tendency of GH to promote fat loss.(ABSTRACT TRUNCATED AT 400 WORDS)

Hypocholesterolemic effect of vegetable protein in a hypocaloric diet

Eleven obese volunteers took part in a 12-week study during 8 weeks of which 2 meals of their control 1000 kcal diets were replaced by a soya based liquid formula (1 month) or a milk based liquid formula (1 month). The mean weight loss per month was 2.5 kg ( P < 0.05). On the soya formula total and LDL cholesterol levels were reduced significantly over the month by 10.0 ± 2.7% ( P < 0.01) and 17.5 ± 5.6% ( P < 0.02), respectively. Neither the milk based formula or the control low calorie diet lowered serum cholesterol significantly over the diet period. No change was seen in serum triglycerides on any of the 3 diets. No difference was seen between treatments in 24-h urinary C-peptide excretion. The results indicated that use of a vegetable protein supplement in a weight loss program which induced moderate weight loss was associated with a reduction in blood lipids, whereas moderate weight loss on a control low calorie diet or milk based formula was not.

Sensitivity and Reproducibility of Urinary C‐peptide as Estimate of Islet B‐cell Function in Insulin‐treated Diabetes

The aims of the present study were to evaluate the ability of urinary C-peptide determination to demonstrate presence of residual insulin secretion, and to evaluate the reproducibility of urinary C-peptide excretion in 125 insulin-treated diabetic patients. C-peptide was determined in two consecutive 24-h urine specimens and related to plasma C-peptide 6 min after the intravenous injection of 1 mg glucagon. The detection limit of C-peptide in plasma was defined analytically (greater than or equal to 0.02 nmol l-1) and from pancreatectomized patients (greater than or equal to 0.06 nmol l-1), and in urine only analytically (greater than or equal to 0.1 nmol l-1). If the analytical detection limit of plasma C-peptide was used as indicator of residual insulin secretion, islet B-cell function was preserved in all patients. In patients with stimulated plasma C-peptide levels from 0.02- less than 0.06 nmol l-1 no increase was found in plasma C-peptide values after stimulation with glucagon. This unresponsiveness of islet B-cells is in good agreement with the existence of a biological detection limit of C-peptide in plasma of 0.06 nmol l-1. Using this biological plasma C-peptide detection limit, 49 of 125 patients were without residual insulin secretion. In contrast to this, only 7 patients were diagnosed as C-peptide nonsecretors using the analytical detection limit of urinary C-peptide. Eighty-four per cent of patients considered to have Type 1 (insulin-dependent) diabetes with a duration of diabetes of more than 15 years had detectable C-peptide in the urine.(ABSTRACT TRUNCATED AT 250 WORDS)

Studies on urinary C-peptide excretion in normal children and children with insulin-dependent diabetes mellitus

In 115 normal children (3 to 14 years old) and 143 children with insulin-dependent diabetes mellitus (6 to 15 years old), the urinary C-peptide immunoreactivity) was measured for evaluation of the pancreatic B cell function. The urinary C-peptide excretions during O-GTT corresponded to the change of serum C-peptide levels in normal children (n = 27) and the mean value of the excretions in younger children was significantly low. Age did not significantly affect basal serum C-peptide levels (ng/ml) and urinary C-peptide excretions (micrograms/h) before O-GTT, but significant differences in serum sigma C-peptide (ng/ml) and urinary C-peptide (micrograms/3 h) during O-GTT were noted between the younger group and the older group (p less than 0.01). In 39 normal children on an inactive routine, mean values of the 24 h urinary C-peptide for children aged from 3 to 6, 7 to 10 and from 11 to 14 years old, were 28.2 +/- 12.6 micrograms/day, 32.3 +/- 8.4 micrograms/day and 37.6 +/- 10.6 micrograms/day (mean +/- SD) respectively with significant differences according to age (younger group vs older group, p less than 0.05). The effects of daily routine on 24 h urinary C-peptide were studied in normal children. In children on an active routine, the C-peptide excretion was significantly less than in the same individuals on an inactive routine (26.9 +/- 9.9 micrograms/day vs 34.3 +/- 14.5 micrograms/day, p less than 0.01). In children with insulin-dependent diabetes mellitus, 24 h urinary C-peptide excretion was studied to evaluate residual pancreatic B cell function. Urinary C-peptide was measurable in 47 of the 143 diabetic children, suggesting that most of the pancreatic B cells had deteriorated in the other 96 patients. In the 96 patients without B cell function, the averages of daily dose of insulin and 24 h-U.glucose/TAG ratio were significantly higher than those in the 47 patients who had pancreatic B cell function estimated by measuring urinary C-peptide (p less than 0.001). In additional studies on the 43 diabetic children with residual pancreatic B cell function, who had had the disease for five years or less, the 24 h urinary C-peptide excretion (micrograms/day) correlated weakly but significantly with the duration of the disease (r = -0.28, p less than 0.05). Patients who had had the disease longer and who were controlled with larger doses of insulin had less of the 24 h urinary C-peptide.(ABSTRACT TRUNCATED AT 400 WORDS)

Metabolic Effect of Hemipancreatectomy in Donors: Preoperative Prediction of Postoperative Oral Glucose Tolerance

Between November 1977 and January 1987, 55 transplantations of pancreas segments from living donors related to their recipients were performed at the University of Minnesota. A preliminary analysis of metabolic test results in donors tested 1 yr after hemipancreatectomy showed an increase in mean glucose and a decrease in mean insulin values during oral glucose tolerance tests (OGTTs) in 18 donors, a 14% increase in the mean of the mean glucose levels during 24-h metabolic profiles in 12 donors, and a decrease of 45% in the mean 24-h urinary C-peptide excretion in 21 donors. Including the studies performed postdonation, 11 of 31 (35%) donors developed an abnormal OGTT result. In a retrospective analysis, preoperative results of intravenous glucose tolerance tests (IVGTTs) and cortisone-stimulated OGTTs were found to be statistically significant predictors of an abnormal OGTT after hemipancreatectomy. The mean of the 5- to 50-min IVGTT insulin values was the best predictive test. With the cutoff value set at 62 microU/ml, this test result had a sensitivity of 100%, a specificity of 83%, and a positive predictive value of 75% for identifying donors who developed an abnormal OGTT. The sum of the 5- and 10-min IVGTT insulin (cutoff 140 microU/ml) had a sensitivity of 100%, a specificity of 67%, and a predictive value of only 60%, whereas the delta-insulin had values of 86, 71, and 60%, respectively. Both the IVGTT mean insulin and the sum of the 5-min and 10-min insulin test results were 100% predictive of an abnormal test (0% risk), but the IVGTT mean insulin excluded the lowest proportion of otherwise suitable donors (a low "false-alarm" rate). The IVGTT mean insulin can be used to identify or exclude potential donors who would develop an abnormal OGTT result should hemipancreatectomy be performed.

Urinary C-peptide: a useful tool for evaluating the endogenous insulin reserve in cohort and longitudinal studies of diabetes in childhood.

Increasing research into the remission phase of type I diabetes mellitus stresses the importance of a non-traumatic and reliable method for the evaluation of endogenous insulin production. We compared 24-h urinary C-peptide excretion (UCE) with plasma C-peptide values before and after stimulation with 1 mg glucagon in 24 type I diabetic children. Fasting plasma C-peptide values and stimulated plasma C-peptide values showed a linear correlation with 24 h UCE. Mean plasma C-peptide levels correlated inversely with the exogenous insulin dose. A slightly better correlation was found between the exogenous insulin dose and 24 h UCE. Control data of 24 h UCE were obtained from healthy siblings. A linear correlation with age was found up to 10 years of age above which UCE values seem to reach a plateau. This effect of age, as well as the frequency of sampling was taken into account in the derivation of 95% reference intervals for UCE. The measurement of 24 h UCE appears to be a useful parameter to assess endogenous insulin production in diabetic children, provided that age is taken into account.

Factors influencing the magnitude, duration, and rate of fall of B-cell function in type 1 (insulin-dependent) diabetic children followed for two years from their clinical diagnosis.

The pattern of fall in B-cell function measured as plasma and 24 h urinary C-peptide excretion, as well as levels of islet cell antibodies, insulin antibodies and metabolic parameters, were followed for two years in 39 children aged 1-17 years prospectively from clinical onset of Type 1 (insulin-dependent) diabetes. At onset 32/36 patients had measurable plasma C-peptide (median 0.13 nmol/l). Maximum values of fasting and postprandial plasma C-peptide were reached at a median duration of three months. Thereafter both plasma and urinary C-peptide declined linearly. The median value of the rate of fall in postprandial plasma C-peptide was 0.019 nmol.1-1.month-1. Age at onset was positively correlated to the maximum value of postprandial plasma C-peptide in each patient (rs = 0.57, p = 0.0001) and throughout the observation time positively correlated to fasting and postprandial C-peptide and to the 24 h urinary C-peptide excretion (rs range 0.35-0.70, p = 0.03-0.0001). The rate of fall of postprandial C-peptide was unrelated to age at onset and was strikingly parallel in different age groups. Islet cell antibodies were present in 87% of the patients at onset and decreased to 38% at 24 months. Islet cell antibody titres were not correlated to age at onset or to plasma or urinary C-peptide at any single observation. However, islet cell antibody negative patients had significantly higher (p less than 0.05) postprandial plasma C-peptide values at 1, 9, and 12 months of duration, compared to islet cell antibody positive patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin antibodies in diabetic children before treatment: a marker for islet B-cell destruction?

Insulin antibodies were measured in the sera of 28 newly diagnosed diabetic children (age 8.0 +/- 4.0 (+/- SD) years) prior to insulin therapy and after 3, 6, 9, and 12 months. The levels at diagnosis and after 12 months were compared to endogenous insulin production at onset and after 12 to 14 months. Endogenous insulin production was evaluated through the measurement of 24-h urinary C-peptide excretion, fasting plasma C-peptide levels and plasma C-peptide levels after glucagon stimulation. Insulin antibodies were detected in 29% of the patients (8 out of 28). In all but one patient antibodies binding porcine and human insulin were detected. No relationship was found between the presence of antibodies binding human or porcine insulin at diagnosis and age. After 1 year 27 out of 28 patients presented insulin antibodies. No relationship was found between the presence of insulin antibodies before therapy and 1 year after therapy. Insulin antibodies prior to diagnosis showed no relationship with the urinary C-peptide excretion at diagnosis (with antibodies 67 +/- 27%, without antibodies 76 +/- 11%). However, after 1 year significantly lower urinary C-peptide excretions were found in patients with insulin antibodies prior to therapy (with antibodies, 17 +/- 7%, without antibodies, 31 +/- 5%, p less than 0.02). Peak plasma C-peptide levels after 1 year were possibly lower in patients with insulin antibodies before treatment (with antibodies 0.17 +/- 0.06 nmol/l, without antibodies 0.26 +/- 0.04 nmol/l, p less than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)

Day-long integrated serum insulin and C-peptide profiles in patients with NIDDM. Correlation with urinary C-peptide excretion.

To determine whether non-insulin-dependent diabetes mellitus (NIDDM) is characterized by day-long hypoinsulinemia, we measured 24-h serum profiles for glucose, insulin, and C-peptide by use of a constant-rate blood-withdrawal technique in diabetic and control subjects fed isocaloric meals. When only lean subjects were considered, diabetic subjects (relative body weight 0.99 +/- 0.3) and control subjects (relative body weight 0.95 +/- 0.03) had similar 24-h integrated serum insulin concentrations (13.4 +/- 2.5 vs. 16.1 +/- 2.0 microU/ml, P NS) due to the offsetting effects of increased basal levels and decreased postprandial responses in NIDDM. In contrast, both basal and meal-stimulated insulin levels were decreased in obese NIDDM subjects (relative body weight 1.39 +/- 0.07) compared with obese control subjects (relative body weight 1.60 +/- 0.08), resulting in a 61% reduction in the 24-h integrated insulin value (18.7 +/- 1.5 vs. 48.4 +/- 13.7 microU/ml). Thus, the capacity to increase 24-h integrated serum insulin as a function of relative body weight was impaired in NIDDM subjects (r = 0.27, P NS) compared with control subjects (r = .70, P less than .01). In contrast, 24-h integrated C-peptide was decreased (P less than .01) in both lean (0.92 +/- 0.13 pM/ml) and obese (1.52 +/- 0.19 pM/ml) NIDDM patients compared with the respective control groups (1.50 +/- 0.13 and 3.03 +/- 0.44 pM/ml). The molar ratio of 24-h integrated C-peptide to insulin was diminished in lean but not obese NIDDM compared with control subjects. A 3-wk period of intensive insulin therapy led to normalization of the mean 24-h integrated insulin (but not integrated serum C-peptide) value in NIDDM compared with a control group that had an identical mean relative body weight. The 24-h urinary C-peptide measured on the same day as the serum profile was correlated (P less than .01) with both the 24-h integrated serum insulin (r = .69) and C-peptide (r = .67) concentrations in control subjects but not in NIDDM subjects (r = .20 and .04, respectively, P NS). Additionally, the urinary clearance of C-peptide was increased in NIDDM (38.1 +/- 7.8 vs. 20.4 +/- 1.7 ml/min in control subjects, P less than .05) and varied with treatment status (26.0 +/- 4.6 ml/min after insulin therapy).(ABSTRACT TRUNCATED AT 400 WORDS)

Day-long integrated serum insulin and C-peptide profiles in patients with NIDDM. Correlation with urinary C-peptide excretion

Day-long integrated serum insulin and C-peptide profiles in patients with NIDDM. Correlation with urinary C-peptide excretion

Effects of lack of exercise on insulin secretion and action in trained subjects.

We employed the hyperglycemic clamp technique to investigate the effects of short-term inactivity on insulin secretion in nine (8 men, 1 woman) well-trained subjects. A 3-h hyperglycemic clamp (plasma glucose approximately 180 mg/100 ml) was performed approximately 16 h after a usual training bout and again 14 days after stopping exercise training. There was no significant change in body composition during this short period of inactivity. The mean plasma insulin response to an identical glycemic stimulus was 67% higher after 14 days without exercise (45 +/- 7 after vs. 27 +/- 4 microU/ml before stopping exercise training). Marked increases in the early (0-10 min, 150 +/- 28 vs. 101 +/- 15 microU.ml-1.min) and late (10-180 min, 6,051 +/- 1,257 vs. 3,521 +/- 749 microU.ml-1.min) incremental insulin areas were observed as a result of the physical inactivity. Incremental areas for C-peptide were also elevated significantly in the inactive state for early (12 +/- 2.0 vs. 7 +/- 1 ng.ml-1.min) and late (567 +/- 90 vs. 467 +/- 85 ng.ml-1.min) phases. Urinary excretion of C-peptide increased from 12.1 +/- 1.5 ng/240 min in the exercising state to 21.8 +/- 3.6 ng/240 min in the inactive state. Rates of whole body glucose disposal were not different between exercising and inactive states, indicating a large increase in resistance to the action of insulin. These findings indicate that the decreased insulin secretory response to a glucose stimulus in people who exercise regularly is a relatively short-term effect of exercise.

Urinary C-peptide in the neonate correlates both to maternal glucose tolerance and to fetal size at birth.

In 18 women with gestational diabetes the variables of an oral glucose tolerance test (fasting and 2-hour blood glucose values and area under the blood glucose curve) performed in the last trimester of pregnancy correlated significantly with the urinary C-peptide excretion during the first 12 hours of the life (r = 0.47, 0.71, and 0.60, respectively). In a combined group with 28 type II pregnant diabetic women there was also a significant correlation between the urinary C-peptide excretion of the infants and their skinfold. Assay of the urinary C-peptide excretion of the neonate, reflecting its insulin production, seems to be a sensitive parameter to study the influence of the maternal carbohydrate metabolism in the offspring.

The beta-cell response to glucagon and mixed meal stimulation in non-insulin dependent diabetes.

The aim of this study was to evaluate the correlations of the C-peptide and insulin responses after stimulation with glucagon intravenously as well as the 24-h urinary excretion of C-peptide to the C-peptide response to a standard mixed meal in 30 patients with non-insulin dependent diabetes mellitus (NIDDM). Fasting plasma C-peptide as well as the C-peptide and insulin responses to glucagon, showed similar but only modest correlations with the C-peptide response to the meal. Urinary C-peptide showed no correlation with the C-peptide response to the meal, but correlated modestly with fasting plasma C-peptide (r = 0.55, p less than 0.01). The C-peptide and insulin responses after meal stimulation correlated modestly inversely with HbA1. In conclusion, measurement of C-peptide in fasting state, as well as measurements of C-peptide and insulin after glucagon stimulation, only modestly predict the C-peptide response to physiologic stimulation in NIDDM. Twenty-four-hour urinary C-peptide excretion does not predict this response. Patients with NIDDM seem to show a better metabolic control if they have a more pronounced beta-cell response to physiologic stimulation.

The effect of short-term basal insulin supplementation with human ultralente insulin on diurnal glycemic control in NIDDM patients

The effect of short-term insulin treatment with a long-acting insulin preparation, Ultratard HM (U-HM) was investigated in eight non-insulin-dependent diabetes mellitus (NIDDM) patients whose previous glycemic control using diet was judged unsatisfactory. The treatment consisted of one daily pre-breakfast injection of U-HM (0.3 IU/kg) for 8 days. Glycemic control, assessed by mean plasma glucose (PG) daily profile and M-value, was improved significantly after U-HM treatment (mean PG and M-value, before: 223 +/- 19 mg/dl, 38.2; on the last day of U-HM: 151 +/- 11 mg/dl, 16.3; P less than 0.001; P less than 0.05). Serum insulin (IRI) reached a peak at 14:30 h during U-HM treatment, and mean IRI level increased during U-HM treatment (before: 14.0 +/- 2.8; during U-HM: 19.9 +/- 2.7 microU/ml). The mean C-peptide (CP) level decreased during U-HM treatment. Daily urinary CP excretion also decreased during U-HM treatment (before: 52.7 +/- 4.2; during U-HM: 34.8 +/- 4.2 micrograms/24 h). The data indicated that a single daily injection of U-HM was effective to improve whole-day glycemic control in NIDDM patients.

Hyperglycemic effects of hydrochlorothiazide and propranolol. A biochemical and ultrastructural study.

The authors studied the glycemic disturbances provoked by two antihypertensive drugs, propranolol and hydrochlorothiazide, administered alone or in combination to normal and diabetic rats, using biochemical and ultrastructural parameters. It was found that hydrochlorothiazide raised fasting glucose concentration significantly; propranolol alone caused an insignificant rise of glucose, but significantly aggravated the effect of hydrochlorothiazide with an additive interaction. The ultrastructural findings, as well as the urinary C-peptide excretion, confirmed that the glycemic effects should not be thought to be due to a direct action of the drugs used on the endocrine pancreas.

Renal Metabolism of C-Peptide in Man*

Renal metabolism of C-peptide was studied in nine nondiabetic nonobese patients with normal renal function by the arterial-venous difference technique before and after the oral administration of an amino acid mixture simulating an animal protein meal. In the basal state, the kidney removed 25.7 +/- 7.5% (+/- SD) of the arterial plasma C-peptide. Renal uptake was approximately 7-fold greater than urinary excretion, and thus, more than 85% of the amount extracted was metabolized by the kidney. Renal C-peptide clearance was very high and approximated the glomerular filtration rate, whereas urinary C-peptide clearance was only 14% of its renal clearance. Shortly after amino acid ingestion, arterial C-peptide levels increased by 107%, and C-peptide renal fractional extraction, uptake, and net metabolism also increased markedly (67%, 278%, and 328%, respectively); urinary clearance and excretion did not change. Renal clearance became 2-fold greater than the glomerular filtration rate, indicating that in this phase the kidney removed substantial amounts of C-peptide from peritubular blood as well as by filtration. Both renal uptake and urinary excretion of C-peptide were related to its arterial levels (P less than 0.001 and P less than 0.05, respectively), but renal uptake increased much more than urinary excretion for each increment in arterial C-peptide levels. These results indicate that renal C-peptide metabolism is considerable in the postabsorptive state and is even more marked during the postprandial period. The kidney, therefore, plays a key role in both the regulation of circulating plasma levels and the metabolic clearance of C-peptide.

Reproducibility of beta-cell function estimates in non-insulin-dependent diabetes mellitus.

We evaluated the reproducibility of different estimates of endogenous insulin secretion in 30 patients with non-insulin-dependent diabetes mellitus (NIDDM). Fasting blood glucose concentration was similar on the 2 days of study. The coefficients of variation of fasting plasma C-peptide, plasma C-peptide 6 min after the injection of 1 mg i.v. glucagon, and the increment in plasma C-peptide after glucagon were 16.0, 14.8 and 24.1%, respectively. The coefficients of variation of the corresponding plasma insulin values were 19.2, 24.8, and 34.8%, respectively. The coefficient of variation of 24-h urinary C-peptide excretion was 22.1%. Because fasting plasma C-peptide correlated closely with plasma C-peptide 6 min after glucagon (test 1: r = .70, P less than .01; test 2: r = .76, P less than .01), it seems that these two values can be used equally well as assessment of beta-cell function in NIDDM. In conclusion, fasting plasma insulin, fasting plasma C-peptide, and plasma C-peptide 6 min after glucagon stimulation showed a similar and acceptable degree of reproducibility. Plasma insulin 6 min after glucagon and increments in plasma insulin and C-peptide, as well as urinary C-peptide, seem to be less reproducible.

Insulin production following injury and sepsis.

It is known that alterations in insulin metabolism following injury and infection result in depression of insulin levels and the development of insulin resistance. In order to further study insulin during septic and traumatic stress, we estimated insulin production in control (Group 1, n = 6), postoperative (Group 2, n = 5), and postoperative-septic (Group 3, n = 8) human subjects by measuring the 24-hour urinary C-peptide excretion. In addition, basal and peak glucose and insulin levels in response to a standard (0.5 gm/kg) intravenous glucose stimulus were measured immediately thereafter to determine if insulin levels reflected insulin production. Basal insulin for Groups 1, 2, and 3 (16 +/- 8.4, 10 +/- 3.4, 9.5 +/- 4.4 microU/ml +/- SD, respectively) were not substantially different. Peak insulin response to glucose infusion declined from Groups 1 to 3 (51 +/- 14, 42.4 +/- 31, 20.4 +/- 6.8 microU/ml, respectively) with Group 3 exhibiting a significantly decreased mean peak level compared to the other groups. Corresponding C-peptide excretion rates increased from Groups 1 to 3 (28.3 +/- 15.3, 63.7 +/- 27.6, 121.3 +/- 95.2 micrograms/day, respectively) with Group 3 exhibiting a significantly (p less than 0.05) higher level than Group 1. These data suggest that low insulin levels which may be evident in injured or septic patients not in shock reflect increased clearance and not decreased production.(ABSTRACT TRUNCATED AT 250 WORDS)

Urinary C-peptide excretion at onset of insulin dependent diabetes mellitus in children.

The 24-hour urinary excretion of C-peptide and the plasma C-peptide concentration were measured at the onset of insulin dependent diabetes mellitus (IDDM) in children. The excretion of C-peptide was twice as high as that found in normal control subjects, whereas the plasma C-peptide values were markedly lower, indicating increased urinary leakage of C-peptide in this phase of the disease. In the diabetic children under seven years of age the mean value of C-peptide excretion was clearly lower than in the older children.