Abnormalities in Circulating Beta Cell Peptides in Chronic Renal Failure: Comparison of C-Peptide, Proinsulin and Insulin

Abstract

Serum insulin, proinsulin and C-peptidewere measured in six patients with chronicrenal failure and 12 controls in the fasting stateand following oral glucose and iv arginine. Fastinglevels of insulin (0.13 ± 0.05 nM vs. 0.05 ± 0.01 nM),proinsulin (0.12 ± 0.06 nM vs. 0.02 ± 0.01 nM) andC-peptide (3.35 ± 1.35 nM vs. 0.65 ± 0.26 nM) werehigher in patients with chronic renal failure than incontrols, the increase in proinsulin (7.5-fold) andC-peptide (4.9-fold) exceeding that of insulin (2.4-fold). Following glucose, insulin rose 11.7 times(60 min) in controls, while the increment in chronicrenal failure patients was less at 7.5-fold (90 min).C-peptide peaked at 3.7-fold (90 min) in controlsand fell toward basal levels at 240 min. In contrast,in chronic renal failure patients, C-peptide peakedlater (180 min) reaching levels of 7.51 nM (1.9-foldincrease), and at 240 min remained near maximumlevels (7.18 nM). The glucose stimulated C-peptidelevels in patients with chronic renal failure weresignificantly higher (P < 0.001) than controls at alltimes. With arginine stimulation in chronic renalfailure patients, C-peptide and insulin incrementswere much lower, with C-peptide levels again beingsignificantly higher (P<0.01) than in controlsthroughout the test. C-peptide and insulin were highly correlated inthe two tests in controls (r = 0.77 with glucose;r = 0.76 with arginine). In chronic renal failure,the correlation approached significance (0.05 ± ± 0.1) following arginine administration, but did notcorrelate after glucose due to different temporalresponses of the two peptides. Renal dysfunction causes marked changes in serumbeta cell peptide levels, and their relative concentrationsmay vary depending upon the quantitativerole which the kidneys play in their removal.Changes in the relationship of C-peptide to insulinmust be considered when interpreting beta cell functionin diabetics and non diabetics with chronicrenal failure.