Urinary C-peptide Excretion Research Articles

Glucose, insulin and C-peptide kinetics during an oral glucose tolerance test in patients with chronic liver disease.

To elucidate the mechanism of glucose intolerance in patients with chronic liver disease(CLD), we measured the levels of plasma glucose, insulin and C-peptide during oral glucose tolerance test and urinary excretion of C-peptide per 24 hours during a weight maintenance diet in 20 patients with CLD who had fasting plasma glucose(FBS) of less than 100 mg/dl.The patients with CLD who had normal FBS(FBS less than 100 mg/dl) were divided into two groups by the National Diabetes Data Group Criteria: one with abnormal glucose tolerance (abnormal GTT, Group 1) and the other with normal glucose tolerance (normal GTT. Group 2). Group 1 patients showed significantly higher plasma insulin (p<0.02 and p<0.01, respectively) and C-peptide concentrations (p<0.01) in the fasting state and 2 hours after a 75gram oral glucose loading (PP2) than group 2 patients. Urinary excretion of C-peptide per 24 hours was also higher in group 1 patients than in group 2 patients (p<0.01). Group 2 patients demonstrated similar plasma insulin, C-peptide and urinary excretion of C-peptide per 24 hours to normal subjects (p>0.05).These results suggest that patients with CLD who had normal FBS can be divided into two groups by oral glucose tolerance test(GTT) and those with abnormal GTT have hyperinsulinemia the mechanism of which is insulin hypersecretion from pancreatic B-cell.

Basal and 24-h C-peptide and insulin secretion rate in normal man.

An understanding of the metabolic abnormalities rising from inappropriate insulin delivery in diabetic patients demands a knowledge of 24-h and basal insulin secretion rates in normal man. We have used biosynthetic human C-peptide to determine its kinetic parameters in 10 normal subjects and applied these to measurements of plasma concentrations in the same subjects to determine pancreatic secretion rate. Metabolic clearance rate measured by stepped primed infusion of biosynthetic human C-peptide at rates of 10, 19 and 26 nmol/h was 4.7 +/- 0.7 (+/- SD) ml X kg-1 X min-1, and was independent of infusion rate. Fractional clearance (T1/2, 26 +/- 3 min) and distribution volume (0.178 +/- 0.039 l/kg) were calculated from the decline in concentration after cessation of the highest rate infusion. Basal insulin secretion calculated from the C-peptide metabolic clearance rate and plasma concentrations for the period 02.00 to 07.00 hours was 1.3 +/- 0.4 U/h. Over 24 h total insulin secretion on a standard high carbohydrate diet was 63 +/- 15 U, calculated from the area under the C-peptide concentration curve. Basal insulin secretion, therefore, accounted for 50 +/- 8% of total insulin secretion. Although only 5.6 +/- 1.1% of C-peptide was detected in 24-h urine collections, urinary C-peptide excretion was significantly related to 24-h C-peptide secretion (r = 0.74, p less than 0.02).

The urinary C-peptide excretion in normal healthy children.

The 24 h urinary C-peptide excretion was determined in 137 normal healthy children, 52 girls and 85 boys, 3-15 years of age. No significant difference was found between boys and girls. Median value of urinary C-peptide for boys and girls was 0.24 nmol/kg/24 h with a range of 0.07-0.61 nmol/kg/24 h. Urinary C-peptide correlated positively and significantly with age, weight, height, body surface area and the 24 h urinary creatinine excretion. Since the values of C-peptide excretion were not normally distributed they were log transformed and plotted against body weight. The linear regression and the 95% confidence limits were then calculated. Girls at puberty, 11-15 years of age, had significantly higher C-peptide excretion per kg body weight and per body surface area than younger girls, 3-10 years of age. Boys 13-15 years of age had significantly higher C-peptide excretion per body surface area than younger boys, 5-12 years of age. This indicates that children during the maximal growth spurt have an increased insulin secretion as measured by urinary C-peptide per body surface area.

Changes in 24 hr Urinary C-peptide Excretion and Serum C-peptide Response after Meal Load in Non-Insulin Dependent Diabetic Patients Following Treatment

Changes in 24 hr Urinary C-peptide Excretion and Serum C-peptide Response after Meal Load in Non-Insulin Dependent Diabetic Patients Following Treatment

High 24-hour urinary C-peptide excretion in non-insulin dependent diabetes mellitus.

The 24-hour urinary C-peptide excretion (UCPR) is a useful means of estimating total daily insulin secretion. To evaluate the daily insulin secretion rate in non-insulin dependent diabetes mellitus (NIDDM), we measured UCPR in 22 patients with NIDDM and 18 normal subjects. The mean (±SD) UCPR in the patients with NIDDM was 115.4±40.2 ug/day and that in normal subjects was 56.7±22.0 ug/day respectively with significantly higher values in the patients with NIDDM (P<0.0001). UCPR was positively correlated with body fat mass determined by measurement of skin fold thickness in both groups [r=0.51 in patients with NIDDM (n=22; p<0.02) and r=0.55 in normal subjects (n=18; p<0.02)], and was higher in NIDDM patients, even with the same degree of fat mass. There was no significant correlation between UCPR and body muscle mass both in the patients with NIDDM and normal subjects [r=0.16 in patients with NIDDM (n=22; p>0.1) and r=0.16 in normal subjects (n=18; p>0.1)]. This result suggested that the total daily insulin secretion rate in NIDDM be increased to compensate insulin resistance, especially that induced by adipose tissues.

Evidence of an accelerated B-cell destruction in HLA-Dw3/Dw4 heterozygous children with type 1 (insulin-dependent) diabetes.

The possible association between residual B-cell function and specific HLA antigens in Type 1 (insulin-dependent) diabetes was studied in a cross-sectional series of 144 diabetic children and adolescents, as well as in a prospective series of 44 newly diagnosed diabetic subjects who were observed for the initial 2 years of their diabetes. In the cross-sectional study, the HLA-Dw3/Dw4 heterozygotes had a lower mean serum C-peptide concentration during 1980, 0.03 +/- 0.01 nmol/l (mean +/- SEM) vs. 0.09 +/- 0.01 nmol/l (p less than 0.02), as well as a lower 24-h urinary C-peptide excretion, 0.27 +/- 0.06 nmol/m2 vs. 1.34 +/- 0.19 nmol/m2 (p less than 0.05), than the other subjects. In addition, the Dw3/Dw4 heterozygotes had a clinical remission of shorter duration, 113 +/- 47 days vs. 203 +/- 22 days (p less than 0.05), and a higher mean glycosylated haemoglobin level during 1980, 14.8 +/- 0.05% vs. 13.7 +/- 0.2% (p less than 0.05), than those without the Dw3/Dw4 combination. In the prospective study the serum C-peptide concentrations were of the same magnitude in the Dw3/Dw4 heterozygotes and the other subjects during the first month. Subsequently the C-peptide concentrations in the subjects with the Dw3/Dw4 combination started to decrease 2 months earlier than in the other subjects. The Dw3/Dw4 children had a significantly lower serum C-peptide concentration at 21 months, 0.01 +/- 0.01 nmol/l vs. 0.13 +/- 0.02 nmol/l (p less than 0.01), and at 24 months, 0.03 +/- 0.01 nmol/l vs. 0.12 +/- 0.02 nmol/l (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Use of urinary C-peptide to estimate insulin secretion during starvation.

The usefulness of measurements of urinary C-peptide excretion in indirectly assessing integrated insulin secretion during starvation was studied in eight obese subjects during a 72-h fast. Blood and urine samples were collected at 12-h intervals for measurement of insulin and C-peptide immunoreactivity. After 60 h, serum insulin and plasma C-peptide levels declined 47% and 37%, respectively, and the values were highly correlated (r = 0.8; P less than 0.001). By 72 h, urinary C-peptide excretion had declined to 70% of the level in the first 12-h period. The urinary clearance of C-peptide was not altered by starvation. A highly significant correlation was found between urinary C-peptide and C-peptide secretory rate (P less than 0.001). The molar ratio of plasma C-peptide to insulin remained constant during the fasting period. These data indicate that basal insulin secretion can be added to the list of physiological conditions in which beta-cell secretion can be effectively evaluated by urinary C-peptide measurement.

The effect of age and body size on the urinary excretion of C-peptide from birth to 14 years of age.

The daily excretion of C-peptide in the urine was measured in 105 healthy infants and children from birth to 14 years of age. For technical reasons no studies were performed from 1-3 years of age. The excretion of C-peptide showed a close positive correlation with age and weight. The relationship with weight was already apparent in the 1st days of life. The C-peptide/weight and the C-peptide/creatinine ratios were constant throughout most of childhood with the exception of the age range of 1 month-1 year when the C-peptide/creatinine was significantly higher. In obese children the C-peptide/weight and C-peptide/creatinine ratios were similar to those found in children with normal weight. In growth hormone deficiency these ratios were low and increased during the 1st week of growth hormone therapy. It is concluded that urinary C-peptide is a reliable indicator of integrated insulin production and gives new information about insulin secretion in various conditions.

Effect of diet restriction on 24-hr urinary C-peptide excretion in non-insulin dependent non-obese diabetic subjects.

Changes in insulin secretory responses by diet restriction were analyzed in non-insulin-dependent non-obese diabetic subjects (NIDDM-NO) as well as in healthy volunteers by determining 24-hr urinary C-peptide immunoreactivity (24-hr UCPR). Insulin sensitivity for glucose utilization was measured by using cyclic somatostatin. Overnight fasting plasma glucose concentrations decreased in NIDDM-NO; however, 24-hr UCPR was reduced in both NIDDM-NO and healthy controls by diet restriction (25 kcal/kg) for 14 days. The level of 24-hr UCPR was higher but insulin sensitivity was lower in NIDDM-NO as compared with those in healthy controls. Therefore, diet restriction may be effective in controlling hyperglycemia and hypersecretion of insulin in NIDDM-NO, but it alone may not improve the reduced insulin sensitivity.

Relationships between insulin secretion, insulin action, and fasting plasma glucose concentration in nondiabetic and noninsulin-dependent diabetic subjects.

The relationships between insulin secretion, insulin action, and fasting plasma glucose concentration (FPG) were examined in 34 southwest American Indians (19 nondiabetics, 15 noninsulin-dependent diabetics) who had a broad range of FPG (88-310 mg/100 ml). Fasting, glucose-stimulated, and meal-stimulated plasma insulin concentrations were negatively correlated with FPG in diabetics but not in nondiabetics. In contrast, fasting and glucose-stimulated plasma C-peptide concentrations did not decrease with increasing FPG in either group and 24-h urinary C-peptide excretion during a diet of mixed composition was positively correlated with FPG for all subjects (r = 0.36, P less than 0.05). Fasting free fatty acid (FFA) was correlated with FPG in nondiabetics (r = 0.49, P less than 0.05) and diabetics (r = 0.77, P less than 0.001). Fasting FFA was also correlated with the isotopically determined endogenous glucose production rate in the diabetics (r = 0.54, P less than 0.05). Endogenous glucose production was strongly correlated with FPG in the diabetics (r = 0.90, P less than 0.0001), but not in the nondiabetics. Indirect calorimetry showed that FPG was also negatively correlated with basal glucose oxidation rates (r = -0.61, P less than 0.001), but positively with lipid oxidation (r = 0.74, P less than 0.001) in the diabetics. Insulin action was measured as total insulin-mediated glucose disposal, glucose oxidation, and storage rates, using the euglycemic clamp with simultaneous indirect calorimetry at plasma insulin concentrations of 135 +/- 5 and 1738 +/- 59 microU/ml. These parameters of insulin action were significantly, negatively correlated with FPG in the nondiabetics at both insulin concentrations, but not in the diabetics although all the diabetics had markedly decreased insulin action. We conclude that decreased insulin action is present in the noninsulin-dependent diabetics in this population and marked hyperglycemia occurs with the addition of decreased peripheral insulin availability. Decreased peripheral insulin availability leads to increased FFA concentrations and lipid oxidation rates (and probably also increased concentrations of gluconeogenic precursors) that together stimulate gluconeogenesis, hepatic glucose production, and progressive hyperglycemia.

Clinical application of the 24-H urinary C-peptide excretion rate and its relationship to metabolic control in diabetics.

In this study, we evaluated in normal subjects, insulin-dependent (IDD) and non-insulin-dependent (NIDD) diabetics, the diurnal urinary C-peptide excretion rate (CPR-U) and its relationship to serum C-peptide concentration and glucose:C-peptide molar ratio, and to the common parameters of metabolic control. The CPR-U (and CPR-U/g creatinine) were significantly lower in IDD and higher in NIDD compared to control subjects. Moreover, a good and significant correlation with serum C-peptide concentrations and the glucose:C-peptide ratio in diabetic subjects as well as in controls and diabetics considered together was found. A slight but significant correlation was present in diabetic subjects between CPR-U and body mass index (r = 0.45), 24-h glycosuria (r = 0.36), HbA1 levels (r = 0.31), post-prandial glucose concentrations (r = 0.26) and per cent glucose variation after each meal (r = 0.34). No differences were found in CPR-U and the degree of metabolic control between obese and non-obese NIDD. In conclusion, CPR-U may be a useful and simple method of defining the secretory activity of the B-cell. Metabolic control in diabetics is slightly correlated to the degree of B-cell function as evaluated by the diurnal excretion rate of C-peptide in urine.

A METHOD FOR EARLY DETECTION OF GRAFT FAILURE IN PANCREAS TRANSPLANTATION

Pancreatic transplantation is intended to normalize carbohydrate metabolism in insulin-dependent diabetics by restoring endogenous insulin release, and it is usually performed together with kidney transplantation in patients with end-stage renal failure. A major problem in these patients is the daily control of the grafted pancreas because traditional measurements do not appear to be adequate to evaluate pancreatic function. Aiming at early detection of graft failure, we have analyzed in 8 such patients and in 20 nondiabetic kidney-grafted patients (a control group) the following variables: 24-hr glycosuria (absolute values, or values after natural logarithmic transformation) and 24-hr urinary C-peptide excretion (corrected for 24-hr urinary creatinine). These measurements, considered alone, did not detect pancreatic graft failure; for instance, glycosuria can depend on immunosuppressive steroid treatment, and it was often found even in the control group. On the contrary, the ratio Ln 24-hr glycosuria: 24-hr urinary C-peptide varied from 0.00 to 0.18 in the control group and in normally working pancreatic grafts; when the pancreatic grafts failed, however, as confirmed by arteriographic evidence, histologic findings, or dynamic endocrine tests, this ratio rose far higher than 0.18, reaching values as high as 12.2. Use of this ratio provides a simple technique for daily evaluation of pancreatic graft function and for early detection of graft failure.

Urinary C-peptide: a simple measure of integrated insulin production with emphasis on the effects of body size, diet, and corticosteroids.

C-Peptide is secreted from the beta-cell in equimolar quantities with insulin. Since a fraction of C-peptide is excreted in the urine, measurement of C-peptide in timed urine collections is a simple indirect measure of integrated insulin production. Normal subjects were studied to determine the effects of diet and oral prednisone on urinary C-peptide excretion. In subjects on a defined diet, there is a positive correlation of urinary C-peptide with body weight. When insulin production is increased after oral prednisone, there is also a positive correlation with body mass index and percent ideal body weight. Prednisone increases plasma glucose, immunoreactive insulin, and serum and urinary C-peptide levels beginning 8-12 h after oral administration. This effect of prednisone is most marked in the postprandial state. Diets high in carbohydrate and protein result in significantly more insulin production, as measured by urinary C-peptide, than isocaloric diets with low protein or carbohydrate composition.

The improved response in endogenous insulin due to continuous subcutaneous infusion of insulin therapy in juvenile diabetes.

We investigated the relationship between the recovery or improved response of endogenous insulin and the control of blood glucose in juvenile diabetes (IDDM) treated with the continuous subcutaneous infusion of insulin (CSII). (1) It is unlikely that the decrease in endogenous insulin secretion over several years following onset of IDDM in 43 subjects was uniform in terms of urinary c-peptide (u-CPR) excretion. (2) In 27 newly diagnosed cases of IDDM, the group receiving CSII (n = 18) showed more satisfactory results, including greater stability of blood glucose, a more rapid decrease in insulin requirements and an earlier improvement in u-CPR compared to the control group who were receiving conventional subcutaneous insulin therapy (n = 9). (3) U-CPR increased with the improvement in blood glucose control within 2 to 4 wks of the initiation of CSII in 6 of 8 already-treated cases of IDDM, while daily insulin requirements did not differ significantly before and after CSII. Since short-term CSII therapy improved u-CPR response by normalizing blood glucose not only in newly diagnosed but also known diabetic, therapy should be directed toward the long-term intensive control of blood glucose in order to maintain the potency of endogenous insulin secretion especially in newly-diagnosed cases of insulin secretion especially in newly-diagnosed cases of IDDM.

Correlation of urinary excretion of C-peptide with the integrated concentration and secretion rate of insulin

Correlation of urinary excretion of C-peptide with the integrated concentration and secretion rate of insulin

The protein-sparing action of protein feeding: absence of relationship to insulin secretion

The influence of a 2-day fast was compared with that of a modified fast (1.5 g beef protein hydrolysate per kg body wt) on nitrogen metabolism and insulin secretion in three normal young men. During the fast urinary urea excretion indicated a negative nitrogen balance of 10 to 12 g daily in each subjects. With protein feeding nitrogen equilibrium was approached in each instance. Insulin secretion as indicated by the urinary excretion of C-peptide dropped profoundly with fasting to levels which averaged just 13 to 22% of the control base-lines and remained at about these levels during the protein feeding. The fact that this sensitive indicator of insulin secretion disclosed no significant difference during fasting and protein feeding provides strong evidence that the protein-sparing influence of protein feeding cannot be ascribed to the decline in insulin secretion.

Sustained insulin-induced remissions of juvenile diabetes by means of an external artificial pancreas.

Remission of diabetes was attempted in 12 recent acute onset ketosis-prone juvenile diabetes after short term (5 +/- 1 days) but excellent blood glucose control by the external artificial beta-cell. The comparison group comrised patients undergoing traditional treatment (n = 28). Nine (75%) persistent (over 3-14 months of duration) although partial (oral drugs required) remissions were obtained in the former group as compared to 3 (11%) in the latter group (p less than 0.05). Cases which showed remissions after insulin infusion had a plasma insulin response to IV glucagon still present before insulin infusion, and a daily urinary C-peptide excretion significantly enhanced after (p less than 0.01). Urinary C-peptide/blood glucose remained improved during the remission period. Thus, early effective treatment by means of the artificial pancreas may break the vicious circle hyperglycaemia-insulin depletion-hyperglycaemia and lead to frequent and sustained remissions of juvenile diabetes.