C-peptide is the "connecting" peptide released from proinsulin after its cleavage in the pancreatic beta-cell. The increase in C-peptide following intravenous injection of glucagon has been used as a measure of residual pancreatic beta-cell function in diabetics. Patients with little or no increase following stimulation have little if any beta-cell function and require insulin for glucose homeostasis. Diabetic patients with sufficient response to stimulation may show adequate glycemic control without the need for exogenous insulin.



(1) Perform an intravenous injection of 1 mg glucagon.

(2) Collect a serum sample 6 minutes after injection and measure C-peptide levels.



• The C-peptide level used to discriminate between those diabetic patients needing insulin and those who do not need insulin is dependent on the assay method used.

• Laakso et al found that insulin was seldom successfully stopped if the postglucagon C-peptide value was < 1 nmol/L, but that insulin therapy could be successfully stopped with values > 1 nmol/L.

• Patients with C-peptide levels > 0.60 nmol/L can sometimes be maintained without insulin, but often need to have insulin therapy restarted.


Procedural notes:

(1) In newly diagnosed obese diabetics, improvement in C-peptide response can be seen after weight loss to ideal body weight.

(2) C-peptide will also increase about 90 minutes following a post-fasting meal (postprandial) in patients with residual beta-cell function. This is due to the glucagon release induced by the meal.

(3) Since meals can affect C-peptide levels, the timing of glucagon stimulation should be standardized relative to pre-test meals, especially after an overnight fast.

(4) Low glucose levels (< 3.5 mmol/L, < 63 mg/dL) were found to suppress the stimulating action of glucagon on the pancreas almost entirely, so can result in false-negative response.


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