Glucose and intermediary metabolite responses during incremental insulin infusion (basal, 0.005, 0.01, and 0.05 U · kg−1 · h−1) were examined in IDDM subjects with duration of diabetes of >5 yr (group D5: n = 8, duration 13.5 ± 3.9 yr, mean ± SD) and <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 < .05). Nonetheless, basal blood glucose (D5 13.8 ± 4.8, D1 7.1 ± 1.5 mM; P < .01), plasma nonesterified fatty acid (NEFA) (D5 1.26 ± 0.12, D1 0.89 ± 0.10 mM; P < .01), blood glycerol (D5 0.12 ± 0.05, D1 0.07 ± 0.02 mM; P < .05), and blood ketones (D5 1.25 ± 0.91, D1 0.26 ± 0.20 mM; P < .01) were higher in group D5.
During insulin infusion, group D5 had significantly elevated plasma free-insulin (P < .05) and blood glucose (P < .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. At an insulin concentration of 30 mU/L, group D5 had elevated blood glucose (D5 12.4 ± 3.1, D1 4.5 ± 1.0 mM; P < .001), plasma NEFA (D5 0.93 ± 0.26, D1 0.54 ± 0.24 mM; P < .01), and ketone (D5 0.97 ± 0.81, D1 0.07 ± 0.03 mM; P < .02) levels.
The results demonstrate insulin resistance in lipolysis, peripheral glucose metabolism, and possibly hepatic glucose metabolism in long-duration compared with short-duration IDDM.
