HYPERGLYCEMIA FACILITATES URINARY-EXCRETION OF C-PEPTIDE BY INCREASING GLOMERULAR-FILTRATION RATE IN NON-INSULIN-DEPENDENT DIABETES-MELLITUS

We have evaluated the feasibility of monitoring the 24-hour urinary ex cretion rate of C-peptide (U-CPR) as a measure of integrated beta-cell function in patients with non-insulin-dependent diabetes mellitus (NI DDM). In 37 normoalbuminuric patients, U-CPR of 117.9 +/- 9.1 mu g/d ( mean +/- SEM) during the poorly controlled glycemic phase (fasting pla sma glucose [FPG], 171 +/- 7 mg/dL; hemoglobin A(1c) [HbA(1c)], 8.8% /- 0.4%) was significantly higher than the value of 83.3 +/- 13.7 mu g /d (P < .001) during the well-controlled phase (FPG, 135 +/- 6 mg/dL; HbA(1c) 7.0% +/- 0.2%), although the plasma insulin response to meals was lower during the former phase (53.3 +/- 6.3 mu U/mL) versus the la tter phase (65.7 +/- 6.6, P < .005). Endogenous creatinine clearance ( Ccr) was significantly elevated during the poorly controlled phase (10 5.4 +/- 7.3 v 88.7 +/- 4.7 mL/min, P < .005). In 26 microalbuminuric p atients, the plasma insulin response was greater during good glycemic control, but U-CPR did not differ between the two phases. Ccr was comp arable at two phases in this group (92.7 +/- 7.4 v 91.1 +/- 5.9 mL/min , NS). U-CPR correlated positively with Ccr in both groups (r = .593, P < .001 in normoalbuminuria; r = .585, P < .001 in microalbuminuria). In addition, when biosynthetic human C-peptide was infused intravenou sly at an identical rate in two healthy subjects, resulting steady-sta te plasma levels of CPR were lower, and fractional U-CPR was higher du ring the moderately hyperglycemic phase versus the euglycemic phase. T he calculated metabolic clearance rate (MCR) of C-peptide was found to be increased in the presence of hyperglycemia. These results suggest that hyperglycemia enhances U-CPR through an increase of glomerular fi ltration rate (GFR), and therefore U-CPR as an index of residual beta- cell function in diabetes should be used cautiously. Copyright (C) 199 5 by W.B. Saunders Company