Eight men with untreated type II diabetes were given 480 mL water containing 15 g, 25 g, 35 g, and 50 g fructose orally, in random sequence. The same subjects were given the same volume of water as a control. They also were given 50 g glucose on two occasions for comparative purposes. Plasma glucose, urea nitrogen, and glucagon, and serum insulin, C-peptide, α-amino-nitrogen (AAN), nonesterified fatty acids (NEFA), and triglycerides were determined over the subsequent 5-hour period. The area responses to each dose of fructose were calculated and compared with the water control. The integrated glucose area dose-response was curvilinear, with little increase in glucose until 50 g fructose was ingested. With the 50-g dose, the area response was 25% of the response to 50 g glucose. The insulin response also was curvilinear, but the curve was opposite to that of the glucose curve. Even the smallest dose of fructose resulted in a relatively large increase in insulin, and a near-maximal response occurred with 35 g. The area response to 50 g fructose was 39% of that to 50 g glucose. The C-peptide data were similar to the insulin data. The AAN area response to fructose ingestion was negative. However, the response was progressively less negative with increasing doses. The glucagon area response was positive, but a dose-response relationship was not apparent. The glucagon area response was negative after glucose ingestion, as expected. The urea nitrogen area response was negative, but again, a dose-response relationship to fructose ingestion was not present. This also was true for the NEFA area response. In summary, the circulating glucose, insulin, and C-peptide area dose-responses are not linear. The insulin and C-peptide response is very sensitive to the ingestion of fructose, whereas there is little glucose response until 50 g fructose is given. The glucagon response to fructose is the opposite of that to glucose, and it is very sensitive to fructose ingestion. Thus, hormonal regulation of liver glucose production is different for glucose and fructose. Inhibition of ureogenesis and fatty acid release from adipose tissue also is very sensitive to fructose ingestion, presumably because of a relatively large increase in insulin concentration. The AAN response to progressively larger doses of fructose was paradoxical and not easily explained.
Bibliographical noteFunding Information:
From the Metabolic Research Laboratory and the Section of Endocrinology Metabolism and Nutrition, Minneapolis Veterans Administration Medical Center; and the Departments of Medicine, and Food Science and Nutrition, University of Minnesota, Minneapolis, MN. Supported by Merit Review Research Funds from the Veterans Administration (FQN and MCG), andf unds from the National Daity Board, administered in cooperation with the National Dairy Council. L.A.B., J.T.L., and K.L.P. were Fellows in Endocrinology at the Minneapolis VA Medical Center. Portions of the data have been previously published: Diabetes 39:47A, 1990 (suppl I, abstr 188). Address reprint requests to Frank Q. Nuttall, MD, PhD, Director, Section of Endocrinology, Metabolism, and Nutrition (1 I1 G), Veterans Administration Medical Center, Minneapolis, MN 55417 Copyright Q I992 by H? B. Saunders Company 00260495192/4105-0012$03.00/O