Multiple aspects of insulin resistance. Comparison of glucose and intermediary metabolite response to incremental insulin infusion in IDDM subjects of short and long duration.

Glucose and intermediary metabolite responses during incremental insulin infusion (basal, 0.005, 0.01, and 0.05 U X kg-1 X h-1) were examined in IDDM subjects with duration of diabetes of greater than 5 yr (group D5: n = 8, duration 13.5 +/- 3.9 yr, mean +/- SD) and less than 1 yr (group D1: n = 8, duration 0.3 +/- 0.1 yr) from diagnosis. Group D5 had significantly elevated basal plasma free-insulin levels (D5 27.4 +/- 9.6, D1 15.5 +/- 9.4 mU/L; P less than .05). Nonetheless, basal blood glucose (D5 13.8 +/- 4.8, D1 7.1 +/- 1.5 mM; P less than .01), plasma nonesterified fatty acid (NEFA) (D5 1.26 +/- 0.12, D1 0.89 +/- 0.10 mM; P less than .01), blood glycerol (D5 0.12 +/- 0.05, D1 0.07 +/- 0.02 mM; P less than .05), and blood ketones (D5 1.25 +/- 0.91, D1 0.26 +/- 0.20 mM; P less than .01) were higher in group D5. During insulin infusion, group D5 had significantly elevated plasma free-insulin (P less than .05) and blood glucose (P less than .01) levels. Isotopically determined glucose turnover showed metabolic clearance rates were significantly diminished in group D5 during all insulin infusions, indicating a marked impairment of peripheral glucose metabolism. In individual subjects the relationship of blood glucose, plasma NEFA, and blood total ketones (log scale) with the simultaneously occurring plasma insulin level (log scale) was linear for each metabolite.(ABSTRACT TRUNCATED AT 250 WORDS)