C-peptide measurement

Katzeff HL, Savage PJ, Barclay-White B, Nagulesparan M, Bennett PH. C-peptide measurement in the differentiation of type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus. Dia-betologia 1985 28 264-8. 

It has been suggested that the easiest way to differentiate between type 1 and type 2 DM is by measuring C-peptide levels. Type 1 diabetics have C-peptide levels below 1 ng/mL (0.33 nmol/L), whereas those with type 2 disease will have values greater than 1 ng/mL (0.33 nmol/L). 

Diagnosis of hypoglycaemia requires that blood glucose concentration be measured before treatment. If the cause is uncertain, samples can be taken to measure the concentrations of insulin, insulin antibodies, and pancreatic C-peptide before the administration of glucose. 

Several tests use glucagon to diagnose endocrine disorders. In patients with type 1 diabetes mellitus, a classic research test of pancreatic beta-cell secretory reserve uses 1 mg of glucagon administered as an intravenous bolus. Because insulin-treated patients develop circulating anti-insulin antibodies that interfere with radioimmunoassays of insulin, measurements of C-peptide are used to indicate beta-cell secretion. 

Chelation of 32 with the 17-residue peptides 33 and 34 (Scheme 20) results in up to 80 and 50% helix, respectively, at 21 °C, as measured by CD spectroscopy. Without the metal complex, 33 is 45% helical, while uncomplexed 34 exhibits the CD spectrum of a random coil structure.11771 Helix induction results from the loss of conformational flexibility of the peptides upon complexation. 

In 17 patients, in whom fasting blood samples were taken immediately before transplantation and at 1 and 3 months after transplantation for measurement of HbA, insulin, C-peptide, free fatty aids, lipids, urea, and creatinine, the incidence of diabetes mellitus was high (47%)... 

With this assay, basal insulin values of 5-15 pU/mL (30-90 pmol/L) are found in normal humans, with a peak rise to 60-90 U/mL (360-540 pmol/L) during meals. Similar assays for measuring all of the known hormones of the endocrine pancreas (including C-peptide and proinsulin) have been developed. 

Insulin [IN suh lin] is a small protein consisting of two polypeptide chains that are connected by disulfide bonds. It is synthesized as a precursor protein (pro-insulin) that undergoes proteolytic cleavage to form insulin and peptide C, both of which are secreted by the p-cells of the pancreas.4 [Note Normal individuals secrete less pro-insulin than insulin, whereas NIDDM patients secrete high levels of the prohormone. Since radioimmunoassays do not distinguish between the two insulin types, NIDDM patients may have lower levels of the active hormone than the assay indicates. Thus measurement of circulating C peptide provides a better index of insulin levels.]... 

Ideally biomarkers of activity should be identified at various times over the course of the study to support the pharmacodynamic activity (e.g., normalization of insulin, improvement in beta cell function as measured by C-peptide level, or control of glucose following transplantation of P pancreatic islet cells) improvement of motor coordination in mice with spinal cord damage following transplant of neurons or repair of heart function (e.g., functional measures such as LV ejection fraction, pressure volume loops, ventricular pressure and heart wall thickness). Such markers may also be useful in subsequent clinical... 

The most definitive laboratory test to distinguish type 1 from type 2 diabetes is the C-peptide assay, which is a measure of endogenous insulin production. With type 2 diabetes, proinsulin can be split into insulin and C-peptide lack of C-peptide indicates type 1 diabetes. The presence of anti-islet antibodies (to glutamic acid decarboxylase, insulinoma associated peptide-2 or insulin) or absence of insulin resistance (determined by a glucose tolerance test) is also suggestive of type 1. 

FIGURE 4.7 Plasma glucose levels after a glucagon injection. Normal (9) and diabetic (O) human subjects were injected with 1.0 mg of glucagon. Plasma glucose and C-peptide levels were measured before and at the indicated times following the injection. (Redrawn with permission from Marchesini ei a ., 1985.)... 

C. Fierens, D. Stockl, D. Baetens, A.P. De Leenheer, L.M. Thieapotal, Application of a C-peptide ESIAsotope dilution-LC-MS-MS measurement procedure for the evaluation of five C-peptide immunoassays for urine, J. Chromatogr. B, 792 (2003) 249. 

Kudolo (37) studied the effect of 3-month ingestion of a GBE on pancreatic (3-cell function. Having taken a 3-month course of GB, 20 normal, healthy subjects were given an oral glucose tolerance test, and fasting plasma insulin and C-peptide were measured. Fasting plasma insulin area under the... 

Clinical Utility of Measuring Insulin, Proinsulin, C-Peptide, and Glucagon... 

Box 25-1 lists the clinical conditions in which hormones that regulate glucose, namely insulin, proinsulin, C-peptide, and glucagon, have been measured. Although there is interest in the possible clinical value of measurement of the concentrations of insulin and its precursors, the assays are useful primarily for research purposes. There is no role for routine testing for insulin, proinsulin, or C-peptide in patients with diabetes mellitus. It must be emphasized that the diagnostic criteria for diabetes mellitus do not include measurements of hormones, which remain predominantly research tools. 

High proinsulin concentrations are usually noted in patients with benign or malignant j3 ceil tumors of the pancreas. Most patients with fl-cell tumors have increased insuhn, C-peptide, and proinsulin concentrations, but occasionally only proinsulin is increased because the tumors have defective conversion of proinsulin to insulin. Despite its low biological activity, proinsuHn production may be adequate to produce hypoglycemia. In addition, a rare form of familial hyperproinsulinemia, produced by impaired conversion to insulin, has been described. Measurement of proinsulin can... 

Accurate measurement of proinsulin has been difhcult for several reasons the blood concentrations are low antibody production is difficult most antisera cross-react with insulin and C-peptide, which are present in much higher concentrations the assays measure intermediate cleavage forms of proinsulin and reference preparations of pure proinsulin are not readily available. However, a more sensitive nonequiUb-rium RIA method for measuring proinsiilin was developed by adsorbing the initial antiserum with biosynthetic human C-peptide coupled to agarose to eliminate cross-reactivity with C-peptide.An enzyme-linked immunosorbent assay (ELISA) has been described that employs an antibody to C-peptide as the coating antibody and antiinsulin antibody for detection. The detection limit is 0.25 pmol/L. ... 

Measurement of C-peptide has a number of advantages over insulin measurement. Because hepatic metabolism is negligible, C-peptide concentrations are better indicators of P-ceU ffinction than is peripheral insulin concentration. Furthermore, C-peptide assays do not measure exogenous insulin and do not cross-react with insulin antibodies, which interfere with the insulin immunoassay. 

Monitoring Therapy. Measurement of C-peptide can be used to monitor patients response to pancreatic surgery. C-peptide should be undetectable after a radical pancreatectomy and should increase after a successful pancreas or islet cell transplant. 

Measurements of urine C-peptide are useful when a continuous assessment of (3-ceU function is desired or frequent blood sampling is not practical. The 24-hour urine C-peptide content (in the absence of renal failure, which produces increased levels) correlates well with fasting serum C-peptide concentration or with the sum of C-peptide concentrations in sequential specimens after a glucose load. However, the fraction of secreted C-peptide that is excreted ill the urine exhibits high intersubject and intrasubject variability, limiting the value of urine C-peptide as a measure of insulin secretion. ... 

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