Assessment of insulin action in man: role of hyperglycemia

The effect of hyperglycemia on insulin-induced glucose metabolism (M) was investigated in healthy subjects using sequential clamp protocols at constant insulin + somatostatin infusions and varying plasma glucose. During euglycemia (4.8 mmol/l) M increased from 5.6 to 12.5 mg·kg−1·min−1 with increasing plasma insulin (0.34-3.00 nmol/l). At increasing glucose (6.7 mmol/l), M further increased (9.7 to 19.2 mg·kg−1·min−1) with the plasma insulin level (0.41 to 2.99 nmol/l). At a plasma glucose level of 9.8 mmol/l insulin (0.42 to 3.17 nmol/l) was still effective to increase M (13.7 to 25.2 mg·kg−1·min−1). Regression analysis showed that hyperglycemia does not only increase the maximal insulin-stimulated M, but also decreases the insulin concentration causing a half maximum effect. During prolonged clamp studies M increased by about 10% per h, independent by the plasma glucose level. We conclude that hyperglycemia increases M by increasing insulin responsiveness as well as insulin sensitivity. Data derived from euglycemic clamp studies alone are of limited value with respect to the assessment of insulin action.