Lack of in Vivo Insulin Resistance in Controlled Insulin-Dependent, Type I, Diabetic Patients*

Publisher Website
Google Scholar
Abstract
Although type I diabetic patients are clearly insulin deficient, it is unclear whether they have normal in vivo sensitivity to insulin. Recent studies which suggested that insulin resistance is a common feature of insulin-dependent diabetics have not taken into account their degree of metabolic control or the presence of circulating antibodies. In the present study, we performed multiple euglycemic glucose clamp studies to construct insulin dose-response curves in 5 well controlled and 5 poorly ontrolled type I diabetic patients and 21 age-matched normal subjects. Each study was performed on a separate day at insulin infusion rates of 15, 40, 120, 240, or 1200 mU/M2-min. During the 40 and 120 ¼U/M2 min infusions, steady state insulin levels of 96 ± 8 (±SE) and 285 ± 27 jiU/ml respectively, were achieved within 25 min in normal subjects. In contrast, diabetic subjectsdid not achieve steady state insulin levels (62 ± 8 and 212 ± 16 /¼U/ml) until 90 min of infusion, and insulin antibodies were detectable in the serum of all these patients. The dose-response curve for insulin stimulation of glucose disposal in well controlled diabetic subjects was comparable to that in normal subjects, with half-max00imally effective insulin levels of 84 /¼U/ml in the diabetic patients compared to 70 ¼U/ml in normal subjects and virtually identical maximal rates of glucose disposal (433 ± 11 vs. 411 ± 17 mg/M2min in controls). In contrast, the dose-response curve for poorly controlled diabetic subjects was significantly rightshifted (half-maximally effective insulin level, 112 /xU/ml), with marked reduction in the maximal glucose disposal rate (324 ± 25 vs. 411 ± 17 mg/M2-min in normal subjects).