Fructose and diabetes

Abstract

The metabolic effects of fructose have been studied in one healthy subject and in eight diabetic patients by observing their metabolic balance while feeding them continuously with a synthetic liquid diet containing fructose as the sole carbohydrate. In each case treatment with insulin was stopped. The mixture was pumped through a tube into the gastrointestinal tract at a slow, constant rate around the clock. Fructose given in this way was completely utilized or stored; none was recovered from the blood or the urine. During continuous feeding with fructose the blood glucose in each patient stabilized at his own particular fasting level, never below it. Glycosuria diminished, or disappeared if the fasting level was below the renal threshold. Coincidentally with the improved utilization of carbohydrate, potassium and phosphate were retained in considerable amounts. By continuously providing a carbohydrate such as fructose which can be utilized without insulin by the patient with diabetes, it was possible in the milder cases to correct or improve the overproduction of acetone, the negative nitrogen balance and the loss of weight, in the complete absence of exogenous insulin. Since no fructose was present in the peripheral blood its effects apparently originated within the liver. These findings confirm and extend those of others in animal experiments, and strongly suggest that the abnormalities of fat and protein metabolism in diabetes are not due to lack of insulin per se but are caused by the impairment of normal utilization of carbohydrate which occurs with insulin deficiency. Fructose was not effective in severe diabetes characterized by high fasting blood glucose levels, intense glycosuria and rapid onset of severe ketosis. Reasons are given for attributing the ineffectiveness of fructose in these patients to an accelerated rate of hepatic glucose release, so that no gain in the amount of carbohydrate available within the liver cell can occur. Knowledge of the mechanisms governing the rate of release of glucose from the liver cells is fragmentary. It is our opinion that the therapeutic usefulness of fructose is slight. Its continuous or very frequent administration is not practical under ordinary circumstances. Of greater importance is the fact that while it bypasses the defect in hepatic glucose uptake, it does not inhibit the accelerated rate of hepatic glucose release. In the severely diabetic patient the latter appears to be a significant metabolic lesion.