It has recently been postulated that hyperglycemia per se may contribute to insulin resistance in diabetes. To examine this possibility directly, we measured glucose uptake after 24 h of hyperglycemia (281 ±16 mg/dl) and normoglycemia (99 ± 6 mg/dl) in 10 type I (insulin-dependent) diabetic patients (age 33 ± 3 yr, relative body wt 102 ± 3%) treated with continuous subcutaneous insulin infusion. Hyperglycemia was induced by an intravenous glucose infusion, whereas saline was administered during the control day. During both studies the patient received a similar diet and insulin dose. After hyper- and normoglycemia, a primed continuous infusion of insulin (40 mU · m−2 · min−1) was started, and plasma glucose was adjusted to and maintained at 142 ± 2 and 140 ± 2 mg/dl, respectively, during 60–160 min of insulin infusion. The rate of glucose uptake after hyperglycemia averaged 8.3 ± 1.1 mg · kg−1 · min−1, which was lower than the rate after the normoglycemic period (10.1 ± 1.2 mg · kg−1 · min−1, P < .001). In conclusion, short-term hyperglycemia reduces glucose uptake in type I diabetic patients. Thus, part of the glucose or insulin resistance in these patients may be caused by hyperglycemia per se.

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