Is exogenous fructose metabolism truly insulin independent?

Although fructose is widely regarded as an insulin-independent fuel source, its in vivo conversion to glucose represents a theoretical limitation to its clinical usefulness in diabetics, particularly if given in large doses. To determine whether small amounts of fructose can be well utilized in the setting of insulinopenia, we administered a low-dose fructose infusion (4.2 g/hr) to a fasting type 1 diabetic patient receiving continuous subcutaneous insulin at a dose that had previously maintained stable euglycemia for 72 hr (plasma glucose = 80-110 mg/dl). Despite the low infusion rate (less than 20% of calorie requirement), fructose caused an immediate and marked rise in plasma glucose (to 370 mg/dl after 27 hr). Glucose loss in the urine and accumulation in plasma could account for fully half of the administered hexose load. Thus, the utilization of even small quantities of exogenous fructose is profoundly impaired under hypoinsulinemic conditions. It is misleading to regard fructose as a truly insulin-independent fuel source.