Insulin-mediated glucose uptake in nondialyzed and dialyzed uremic insulin-dependent diabetic subjects

A three-step euglycemic insulin clamp was performed in six matched groups: nine healthy subjects, 10 insulin-dependent diabetic (IDD) subjects with normal kidney function, 10 nondiabetic uremic subjects, six nondialyzed uremic IDD subjects, seven uremic IDD subjects on chronic hemodialysis (HD), and six uremic IDD subjects on chronic ambulatory peritoneal dialysis (CAPD). Insulin was infused sequentially at rates of 0.5 (step 1), 2.0 (step 2), and 4.0 (step 3) mU X kg-1 X min-1. Each dose was given for 120 min; however, in the IDD subjects with fasting hyperglycemia, step 1 of the clamp was slightly extended. Average serum free insulin levels at steady state ranged from 22 to 342 microU/ml and were comparable in all groups. Step 3 glucose infusion rate (GIR), the last 30 min of the infusion period, was extremely suppressed in nondialyzed uremic IDD subjects, amounting to 53% of that in healthy subjects (7.7 +/- 0.7 versus 14.4 +/- 0.9 mg X kg-1 X min-1, P less than 0.001) indicating severe insulin resistance in peripheral tissues. As expected, step 3 glucose disposal was also reduced in IDD subjects with normal kidney function (12.4 +/- 0.6 mg X kg-1 X min-1) and nondiabetic uremic subjects (9.2 +/- 0.6 mg X kg-1 X min-1) as compared with healthy subjects (P = 0.06 and P less than 0.001, respectively). The pronounced impairment of insulin responsiveness in nondialyzed uremic IDD subjects was almost equal to the sum of the defects in nondiabetic uremic and IDD subjects with normal kidney function.(ABSTRACT TRUNCATED AT 250 WORDS)