To clarify whether type I diabetes is characterized by insulin resistance, insulin-mediated glucose metabolism (M; milligrams per kg/min) was estimated by means of the glucose clamp technique in 5 insulin-dependent patients and 6 normal subjects. Three glucose clamps were carried out under different metabolic conditions. Free insulin plateaux were similar during each clamp in both groups. The first clamp was performed in normal subjects after an overnight fast [blood glucose, 80 ± 3 mg/dl (mean ± SEM)] and in diabetic patients 18 h after insulin withdrawal (blood glucose, 366 ± 47 mg/dl). Diabetic patients had a M value (4.25 ± 0.74) not different from normals (5.38 ± 0.63; P = NS). The second clamp was done with the same glycemic values (~125 mg/dl) in both groups. M increased to 8.07 ± 1.06 (P < 0.01) in the normal subjects and decreased to 2.87 ± 0.50 (P = NS) in the diabetic patients. The M value in the diabetic patients was lower than that in the normal subjects (P < 0.05). The third clamp was performed in 3 diabetic patients after 1 month of treatment with continuous sc insulin infusion. The mean blood glucose level was 88 ± 6 mg/dl, and M was 3.23 ± 0.38, significantly lower than that of the normal subjects in the basal state (P < 0.05). No differences were found in insulin binding to erythrocytes. The mean plasma clearance rate (milliliters per m2/min) of free insulin was the same in both groups (428 ± 113 in normal subjects and 354 ± 83 in diabetic patients). Basal endogenous glucose production was higher in the diabetics (3.13 ± 0.48 mg/kg.min) than in the normal subjects (1.71 ± 0.57). During the clamp, however, endogenous glucose production was similarly inhibited (~95%) in both groups. Multiple glucose clamp studies were also performed at three different insulin infusion rates (21, 73, and 760 mU/m2.min, respectively) to generate an insulin-dose response curve for glucose disposal in 6 diabetic patients treated with continuous sc insulin infusion for at least 6 months. This allowed investigation of the effect of chronic strict insulin therapy leading to normal glucose and intermediary metabolite levels and identification of the cellular mechanism of insulin resistance. A significant reduction of the maximal glucose disposal rate (10.7 ± 0.5 mg/kg.min) was found in these diabetic patients compared to that in normal subjects (14.9 ± 1.0; P < 0.05). No difference was found in the half-maximally effective insulin levels. The inhibition-competition curve for insulin binding to erythrocytes was the same in both groups. These data indicate that insulin resistance is a feature of type I diabetes. The impairment of insulin action is related to a postreceptor defect, which was not normalized by 6 months of strict insulin therapy.
Insulin-mediated glucose disposal in type 1 diabetes: evidence for insulin resistance
DEL PRATO, STEFANO;
1983-01-01
Abstract
To clarify whether type I diabetes is characterized by insulin resistance, insulin-mediated glucose metabolism (M; milligrams per kg/min) was estimated by means of the glucose clamp technique in 5 insulin-dependent patients and 6 normal subjects. Three glucose clamps were carried out under different metabolic conditions. Free insulin plateaux were similar during each clamp in both groups. The first clamp was performed in normal subjects after an overnight fast [blood glucose, 80 ± 3 mg/dl (mean ± SEM)] and in diabetic patients 18 h after insulin withdrawal (blood glucose, 366 ± 47 mg/dl). Diabetic patients had a M value (4.25 ± 0.74) not different from normals (5.38 ± 0.63; P = NS). The second clamp was done with the same glycemic values (~125 mg/dl) in both groups. M increased to 8.07 ± 1.06 (P < 0.01) in the normal subjects and decreased to 2.87 ± 0.50 (P = NS) in the diabetic patients. The M value in the diabetic patients was lower than that in the normal subjects (P < 0.05). The third clamp was performed in 3 diabetic patients after 1 month of treatment with continuous sc insulin infusion. The mean blood glucose level was 88 ± 6 mg/dl, and M was 3.23 ± 0.38, significantly lower than that of the normal subjects in the basal state (P < 0.05). No differences were found in insulin binding to erythrocytes. The mean plasma clearance rate (milliliters per m2/min) of free insulin was the same in both groups (428 ± 113 in normal subjects and 354 ± 83 in diabetic patients). Basal endogenous glucose production was higher in the diabetics (3.13 ± 0.48 mg/kg.min) than in the normal subjects (1.71 ± 0.57). During the clamp, however, endogenous glucose production was similarly inhibited (~95%) in both groups. Multiple glucose clamp studies were also performed at three different insulin infusion rates (21, 73, and 760 mU/m2.min, respectively) to generate an insulin-dose response curve for glucose disposal in 6 diabetic patients treated with continuous sc insulin infusion for at least 6 months. This allowed investigation of the effect of chronic strict insulin therapy leading to normal glucose and intermediary metabolite levels and identification of the cellular mechanism of insulin resistance. A significant reduction of the maximal glucose disposal rate (10.7 ± 0.5 mg/kg.min) was found in these diabetic patients compared to that in normal subjects (14.9 ± 1.0; P < 0.05). No difference was found in the half-maximally effective insulin levels. The inhibition-competition curve for insulin binding to erythrocytes was the same in both groups. These data indicate that insulin resistance is a feature of type I diabetes. The impairment of insulin action is related to a postreceptor defect, which was not normalized by 6 months of strict insulin therapy.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
