Serum C-peptide Responses Research Articles

A comparison of serum C-peptide response to intravenous glucagon, and urine C-peptide, as indexes of insulin dependence

Serum C-peptide (SCPR) at fasting and after intravenous injection of glucagon was evaluated in diabetic patients with various degrees of insulin dependence, and compared with 24 h urine C-peptide (UCPR). Fasting SCPR did not differ between healthy subjects and sulfonylurea-treated patients (SU) who were considered to have definite non-insulin-dependent diabetes (NIDDM); but was significantly lower in patients with insulin-dependent diabetes (IDDM) (0.24 +/- 0.10 ng/ml in IDDM vs. 1.43 +/- 0.61 ng/ml in SU, P less than 0.001). SCPR reached a peak at 6 min after glucagon injection, except for the IDDM group. The SCPR response at 6 min after 1 mg glucagon injection was significantly lower in the SU (NIDDM) group than in the normal group (2.86 +/- 1.21 v. 4.69 +/- 1.47 ng/ml, P less than 0.001). In the IDDM group, there was no increase of SCPR after glucagon injection. Among diabetic patients, SCPR response to glucagon correlated positively to the amounts of UCPR (P less than 0.001). By analysis of the distribution patterns of SCPR response to intravenous glucagon, SCPR of 1.0 ng/ml and the increment of SCPR of 0.5 ng/ml at 6 min are to be used as cut-off points to differentiate IDDM and NIDDM. These values correspond roughly to the UCPR values below 20 micrograms/day and above 30 micrograms/day, which we previously proposed as indexes to differentiate insulin-dependent and non-insulin-dependent diabetes.

Exercise-induced hepatic glucose output is precisely sensitive to the rate of systemic glucose supply

It has previously been established that a glucose infusion causing hyperglycemia and alterations in the levels of glucoregulatory hormones suppresses the exercise-induced increment in systemic glucose appearance (R a). In an attempt to define the mechanisms responsible for this suppression of R a, five normal subjects were exercised for 60 minutes on a bicycle ergometer at 60% V̇o 2 max on two occasions. On both occasions R a was measured by a nonsteady state technique using a constant infusion of 3- 3H-glucose. On the second occasion, an IV infusion of glucose was administered in a stepwise fashion to simulate in timing and magnitude the measured R a response from the first study. Endogenous glucose production in the second study, estimated by subtracting the amount of glucose infused from the measured R a response, did not increase above basal ( endogenous glucose output response = 0.5 ± 8.4 mmol 60 min v control study 60.2 ± 6.6 mmol 60 min , P < 0.01 ). The suppression of R a was associated with a small but significant effect on venous plasma glucose (increment above basal less than 0.3 mmol/L, P < 0.05) and a significant change in glucose metabolic clearance rate during the second 30 minutes of exercise. Serum insulin, C-peptide, cortisol, growth hormone, and plasma glucagon responses to exercise were not significantly affected by glucose infusion and the ratio of circulating insulin to glucagon was also not affected. These results indicate that hepatic glucose output during exercise is precisely sensitive to glucose supply. The feedback inhibition is presumably mediated by a small increase in plasma glucose but cannot readily be accounted for by changes in glucoregulatory hormones. A direct or indirect non hormonal feedback effect of blood glucose on hepatic glucose output is suggested.

Meal-stimulated C-peptide and insulin antibodies in type I diabetic subjects and their nondiabetic siblings characterized by HLA-DR antigens.

We studied serum C-peptide (CP) response 90 min after a breakfast meal and insulin antibody titers in 171 type I diabetic (IDDM) patients and 272 of their nondiabetic siblings from 169 unrelated families. HLA typing was performed in all participants. In IDDM patients, there was a decline in CP response with increased duration of disease. CP responses of greater than or equal to 1.8 ng/ml were seen significantly less often in patients who were less than 10 yr old at the time of diagnosis of IDDM than in patients who were greater than 10 yr old at the time of diagnosis (8% versus 21%, P less than 0.05). More patients with HLA-DR4 had a CP response greater than or equal to 1.8 ng/ml than did patients who lacked this antigen whether duration of IDDM was less than 10 yr (30% versus 18%, P greater than 0.05) or greater than or equal to 10 yr (15% versus 0%, P less than 0.05). Mean C-peptide was also higher in HLA-DR4-positive patients compared with HLA-DR4-negative patients both when duration of disease was less than 10 yr (1.7 +/- 1.9 versus 1.4 +/- 1.0, P less than 0.01) and greater than or equal to 10 yr (1.2 +/- 1.5 versus 1.0 +/- 0.4, P less than 0.0001). Insulin antibody binding was slightly higher in patients with HLA-DR4 compared with patients lacking this antigen (5.96 +/- 7.20 versus 4.89 +/- 4.74, P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

C-Peptide responses to glucose load in maturity-onset diabetes of the young (MODY).

Pancreatic beta cell responses were measured in obese and nonobese maturity-onset diabetes of the young (MODY) patients by estimating serum immunoreactive insulin (IRI) and C-peptide (CP) during oral glucose tolerance testing (OGTT). The serum CP responses were generally low in MODY patients and more pronounced in obese patients. The IRI responses were heterogenous; some patients had normal and others low responses. It was observed that in several patients there was a relatively higher IRI concentration in comparison with the CP values, as indicated by low CP and normal IRI values. This is suggestive of altered metabolic fates of insulin and CP in the MODY patients.

Significance of spontaneous ketonuria and serum C-peptide levels in obese type II diabetic patients.

Patients with type II diabetes mellitus (type II DM patients) are characteristically obese, hyperinsulinemic, and non-ketosis prone. Recently, we have encountered several obese type II DM patients with either diabetic ketoacidosis or significant ketonuria after insulin withdrawal. There was no evidence of infection, stress, or starvation to explain their ketonuria. Therefore, we assessed serum connecting peptide (C-peptide) response to oral glucose in 14 obese, insulin-treated type II DM patients: 6 with and 8 without episodes of spontaneous ketonuria. The group presenting with ketonuria had low to absent basal and stimulated serum C-peptide responses. The nonketonuric group had higher basal C-peptide (P less than 0.01) concentrations that increased significantly (P less than 0.001) after oral glucose compared with those of the ketonuric group. Clinical characteristics and biochemical control were similar in both groups. Our findings confirm that obese type II diabetes mellitus is a heterogeneous disease with variable fasting and stimulated C-peptide responses. Spontaneous ketonuria could be a feature in the clinical presentation of the patients especially in the presence of both low fasting and stimulated C-peptide levels. The significance of these findings is unclear but suggests individualization in the management of type II DM patients and cautious withdrawal of insulin therapy in such patients. Furthermore, serum C-peptide levels alone cannot be recommended to classify patients into either type I or type II diabetes mellitus.

A prospective analysis of islet-cell cytotoxic antibodies in insulin-dependent diabetic children. Transient effects of plasmapheresis.

We determined the effects of plasmapheresis on cytotoxic antibodies to islet cells in 10 children (aged 11-16 yr) with newly diagnosed insulin-dependent diabetes mellitus (IDDM), as well as the plasma levels of antibodies over the next 30 mo and their relation to serum C-peptide concentrations. Complement-dependent, antibody-mediated cytotoxicity (C'AMC) in plasma was measured in a 51Cr release assay using monolayers of the rat islet cell line RINm5F. Cytotoxic antibodies decreased in most IDDM subjects treated by plasmapheresis four times within 2 wk of diagnosis; however, the decreases were small and lasted less than 2-3 days. Thus, both before and after plasmapheresis, 7 of the 10 IDDM children were C'AMC-positive (51Cr release greater than 2 SD above mean for 13 healthy children). After 18-30 mo, only 2 of the original 7 IDDM children with C'AMC-positive plasmas were still positive, and 1 of the original 3 IDDM children without significant cytotoxicity had become positive. Meal-stimulated serum C-peptide responses, measured from diagnosis to 18-30 mo later, did not correlate with C'AMC values. We conclude that (1) plasmapheresis has only transient effects on islet-cytotoxic antibody levels in children with IDDM; (2) these antibodies decrease in most, but not all, subjects over the first 18 mo after diagnosis; and (3) the level of cytotoxic antibodies in IDDM plasma at diagnosis has no predictive effect on residual B-cell function.

Pancreatic α-Cell Function in Diabetic Hemochromatotic Subjects*

To clarify further the etiology of the carbohydrate intolerance in idiopathic hemochromatosis, we investigated the glucose, insulin, C-peptide, and glucagon responses to arginine (0.5 g/kg) infused during 30 min in lean normal subjects; in insulin-requiring subjects with hemochromatosis, genetic diabetes, and total pancreatectomy; and in nondiabetic cirrhotic subjects without portosystemic shunting. Serum insulin, C-peptide, and glucagon responses (30K antibody) were determined by RIA, and glucose level was determined by a glucose oxidase technique. Hemochromatotic and genetic diabetic subjects had similar basal glucose (157 +/- 25 vs. 168 +/- 40 mg/dl) and C-peptide (0.73 +/- 0.42 vs. 0.65 +/- 0.22 ng/ml) values, with subnormal C-peptide peak responses to stimulation (1.05 +/- 0.38 and 1.40 +/- 0.83 vs. 3.95 +/- 0.4 ng/ml in normals; P less than 0.05). No glucagon or C-peptide response to arginine was seen in any pancreatectomized subject. Similar but excessive glucagon levels were present in hemochromatosis, diabetes, and cirrhosis under basal conditions (166 +/- 24, 232 +/- 111, and 263 +/- 116 vs. 76 +/- 15 pg/ml; P less than 0.05) and after arginine stimulation (782 +/- 80, 834 +/- 123, and 902 +/- 275 vs. 489 +/- 81 pg/ml; P less than 0.05) when compared with normals. The excessive glucagon levels found in hemochromatosis, diabetes mellitus, and cirrhosis contrast to the absent response in pancreatectomized subjects and indicate that generalized islet cell destruction is not the major factor in diabetic hemochromatotic subjects.

Clinical Studies on the Serum C-peptide Responses to Oral Administration of 50g Glucose.

Clinical Studies on the Serum C-peptide Responses to Oral Administration of 50g Glucose.