Renal metabolism of C-peptide in patients with early insulin-dependent diabetes mellitus.

Renal metabolism of C-peptide was studied in 6 patients with early insulin-dependent diabetes mellitus (IDDM) with residual beta cell activity and in 11 nondiabetic subjects by the arterial-venous difference technique both in the postabsorptive state and for 80 min after ingestion of an amino acid mixture (0.8 g/kg). Urinary C-peptide (Cp) excretion, glomerular filtration rate and renal plasma flow were also measured. In the postabsorptive state in IDDM, renal uptake of Cp is reduced, while its urinary excretion and clearance are significantly increased. As a result, net renal extraction is markedly reduced. In contrast to controls, renal uptake and net extraction of C-peptide after amino acid ingestion do not increase in patients; the peritubular uptake evident in normal subjects is not detectable. Urinary excretion and clearance of Cp remain significantly higher in IDDM patients. In both groups, renal uptake of C-peptide is directly related to its renal load: however, in IDDM, the increase in Cp uptake for each increment in renal load is 35% lower than in controls (p < 0.001). Furthermore, as opposed to controls, urinary Cp excretion is not correlated with its arterial levels. Therefore IDDM patients have marked defects in renal handling of endogenous Cp, regarding both the amount metabolized by renal tissue and that reabsorbed by tubular cells. These data indicate an early alteration in the diabetic kidney that also impairs the reliability of urinary Cp evaluation as an index of residual beta cell activity in IDDM patients.