Direct methods for measuring the secretion rate of insulin are too cumbersome for clinical application. Since C-peptide is secreted in an equimolar ratio with insulin and is excreted into the urine, measuring the urinary excretion rate of C-peptide (U-C) could serve as an indicator of its secretion rate (SR-C) if its urinary clearance (UCI-C) is constant and unaffected by plasma C-peptide concentration, body mass, or diabetes.

We measured clearance ratios of C-peptide/creatinine (CR) in the fasting state and integrated 0–1, 1–3, and 3–5 h after 100 g of glucose p.o. as well as over a full 24-h in eight obese, eight lean, and six maturity-onset diabetic subjects. CR did not differ significantly when values in the fasting state were compared with those in the postprandial periods and was therefore unaffected by plasma C-peptide concentration. Furthermore, CR was similar in the lean, obese, and diabetic subjects. SR-C, determined as the product of the metabolic clearance rate of C-peptide and its fasting or integrated plasma concentrations, correlated significantly with U-C in all the subjects (r = 0.87, P < 0.0001). The correlation of U-C with SR-C in the diabetic subjects alone was also significant (r = 0.88, P < 0.0001). In conclusion, our data support the use of U-C as an indirect measure of SR-C and therefore of SR-I.