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We know that Insulin is secreted as a prohormone, proinsulin which is cleaved by a
membrane pro tease into a biologically active substance insulin and equimolar amounts of C-peptides a relatively inert molecule, with no known bioactivity.
C-peptide is a peptide molecules with 30-40 aminoacid linked with peptide bonds. This
variation in chain length is due to proinsulin which itself is a 78-86 A. A. containing molecules once C-peptide are secreted by B-cell into the circulation, they are little affected by hepatic extraction, Strikingly in contrast to insulin, which can be extracted by liver during first pass phenomenon to a variable amount. Sometimes exceeding half of the total insulin secreted, while C-peptides find their way into circulation. It is due to this difference the usual C-peptide level is 30-130 u/ml almost five times the normal insulin level in blood.
Clinocal indications of C-peptide estimation
It is stressed repeatedly that meticulous glycemic control can delay or prevent the rapid
progress of chronic complications of diabetes e.g. retinopathy, neuropathy, nephropathy. This control is achieved by either OHA or exogenous insulin therapy. On the other hand injudicious use of their agent or insulin also increases the risk of cardiovascular mortality through increased atherogenesis. So we should be well informed about the patients insulin need or to say endogenous insulin secreting capacity. Which can be easily judged by C-peptide assays and other stimulation test (glucagon stimulation test, tolbutanmide stimulation test)
Uses :
1. Evaluation of B-cell reserve
2. Delineation of IDDM patients :- Patients is who have little C-peptides in their blood are
better controlled with exogenous insulin therapy than those who do not, thus helping to
assess the severity of IDDM. The beginning and honeymoon phase of type I diabetes
mellitus can be assessed by C-peptide assay.
3. Ill-controlled Glycemia :- Wide fluctuations in plasma glucose show inverse relationship
with C-peptide assay.
4. Differential diagnosis of hypoglycemia due to insulinoma from other causes of
hypoglycemia.
Hypoglycemia C-peptide
a. Insulinoma + Increases
b. Exogenous , + Decrease
c. Factitious
hypoglycemia
(medical health
workers etc) + Decrease
d. Sulfonyl urea + Increase
Hence in sulphonylurea induced hypoglycemia serum OHA drug levels will be
confirmatory in addition to increased C-peptide levels.
5. Adequacy of Pancreatectomy for malignant insulinoma Serial C-peptide level
measurement is done so as to rule out recurrence.
6. Judging the efficacy of OHA :- Sulfonylurea have endogenous insulin as well as C-
peptide secretion.
7. Brittle diabetes: If C-peptide levels are decreased the ill-managed diabetes is due to
exhaustion of B-cells and exogenous insulin is required for further m/m. If C-peptide level is not much reduced the problem is with patient dietary and therapeutic compliance.
8. Evaluation of role of liver in glucose homeostasis
C-peptide assay : Problems ;
1. Antibodies against proinsulin are also cross reactive with C-peptides, so as to increase
11/2 of C-peptide, thus false elevation may occur. Conditions, which can lead to this, are, Insulinomas, CRF, Thyrotoxicious, cirrhosis acromegaly and obesity. These antibodies can be removed by ethyleneglycol leaving C-peptide free in solution which can be easily estimated.
Causes of increase C-peptide level in blood
a. Insulinoma
b. Cushing's disease.
c.. Insulin resistant stated eg. NIDDM (early stage)
d. Acromegaly - anti insulin antibodise
e. Drugs - Sulfonyl urea (Metformin / Glipizide etc)
Quinine / Pentamidine / Disopyramide
f. Tumors,
g. Dietary factors, leucine / arginine / ? Zinc.
Decrease C-peptide level
Insulinopenic states
a. Acute pancreatitis
b. Chronic pancreatitis
c. Total pancreartectomy
d. IDDM - B-cell destrucion (Auto immune insulitis)
e. NIDDM - B-cell exhaustion
f. Drugs - B-blockers / PZA. etc.
Diazoxide / Streptozocin)
g. Ca-pancreas
h. Tumor infiltration (metastatic)
i. Portal vein Thrombosis / Fibrosis
Contra indication of C - Peptide assay : 1)IHD, 2)Epilepsy, 3) CVA etc.
May cause false elevation of C-peptide.
REFERENCES
1. MMS Ahuja - Insulin in Relation to Diabetes. Practice of Diabetes Mellitus Page
26,1983. Edited by MMS Ahuja; Vikas Publication, New Delhi.
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