THE CONTRIBUTION OF PROINSULIN AND DES-31,32 PROINSULIN TO THE HYPERINSULINEMIA OF DIABETIC AND NONDIABETIC CIRRHOTIC-PATIENTS

We used specific, monoclonal antibody-based, two-site immunoradiometri c assays to test the hypothesis that serum levels of proinsulin and de s-31,32 proinsulin would be increased in cirrhosis, particularly in th ose with overt diabetes. A 75-g oral glucose tolerance test was perfor med after an overnight fast in eight cirrhotic patients with diabetes (fasting blood glucose, 7.8 +/- 2.2 [SE] mmol/L), seven nondiabetic ci rrhotic patients, and eight normal control subjects. Easting serum imm unoreactive insulin levels were approximately six times higher in cirr hotics than in controls, but were not different between diabetic and n ondiabetic cirrhotic patients. After oral glucose, the incremental are a under the serum insulin concentration curve was 3,475 +/- 1,009 pmol .L(-1).h in nondiabetic cirrhotic patients, significantly higher than in controls (761 +/- 48, P < .001) or diabetic cirrhotic patients (881 +/- 186, P < .05). Easting serum proinsulin levels in diabetic cirrho tic patients (24.0 +/- 5.7 pmol/L) were higher than in controls (2.3 /- 0.5, P < .001) or nondiabetic cirrhotic patients (4.4 +/- 0.8, P < .005). Easting serum levers of des-31,32 proinsulin were also much hig her in diabetic cirrhotic patients than in nondiabetic cirrhotic patie nts or controls (P < .02 and P < .005, respectively). Easting proinsul in plus des-31,32 proinsulin constituted 12.5% +/- 1.4% of serum immun oreactive insulin in diabetic cirrhotics, higher than in nondiabetic c irrhotics (3.7% +/- 0.5%, P < .001) and normal controls (7.8% +/- 1.5% , P = .035). The fasting proinsulin to C-peptide molar ratio was signi ficantly higher in diabetic cirrhotic patients (25.1 +/- 8.6) than in controls (6.3 +/- 1.4) or nondiabetic cirrhotic subjects (4.9 +/- 1.4; P < .05 for both). In diabetic cirrhotic patients, proinsulin correla ted with fasting blood glucose levels (r = .95, P < .001), as did des- 31,32 proinsulin (r = .87, P < .01), proinsulin as a proportion of imm unoreactive insulin (r = .82, P < .02), and the proinsulin to C-peptid e molar ratio (r = .87, P < .005). Proinsulin levels were increased in both diabetic and nondiabetic cirrhotic patients, but a disproportion ate elevation relative to insulin and C-peptide was seen only in diabe tic patients. Compared with findings in type II diabetes, the changes in proinsulin as a proportion of total immunoreactive insulin were sma ll (< 15%) because insulin clearance is impaired in cirrhosis. Copyrig ht (C) 1995 by W.B. Saunders Company