Metabolic Effects of Reducing Rate of Glucose Ingestion by Single Bolus Versus Continuous Sipping DAVID J.A. JENKINS, THOMAS M.S. WOLEVER, ANTHONY M. OCANA, VLADIMIR VUKSAN, STEPHEN C. CUNNANE, MARK JENKINS, GERALD S. WONG, WILLIAM SINGER, STEPHEN R. BLOOM, LAWRENCE M. BLENDIS, AND ROBERT G. JOSSE Modifying the rate of absorption has been proposed as a therapeutic principle of specific relevance to diabetes. To demonstrate clearly the metabolic benefits that might result from reducing the rate of nutrient delivery, nine healthy volunteers took 50 g glucose in 700 ml water on two occasions: over 5-10 min (bolus) and at a constant rate over 3.5 h (sipping). Despite similar 4-h blood glucose areas, large reductions were seen in serum insulin (54 ± 10%, P < 0.001) and C-peptide (47 ± 12%, P < 0.01) areas after sipping, together with lower gastric inhibitory polypeptide and enteroglucagon levels and urinary catecholamine output. There was also prolonged suppression of plasma glucagon, growth hormone, and free-fatty acid (FFA) levels after sipping, whereas these levels rose 3-4 h after the glucose bolus. An intravenous glucose tolerance test at 4 h demonstrated a 48 ± 10% (P < 0.01) more rapid decline in blood glucose (K g ) after sipping than after the bolus. Furthermore, FFA and total branched-chain amino acid levels as additional markers of insulin action were lower over this period despite similar absolute levels of insulin and C-peptide. These findings indicate that prolonging the rate of glucose absorption enhances insulin economy and glucose disposal. Diabetes 39:775-81, 1990 W e have recently demonstrated that increased meal frequency results in a 20% reduction in daylong insulin secretion associated with marked falls in low-density lipoprotein choles- terol and apolipoprotein B in healthy volunteers (1). It is increasingly recognized that delaying nutrient absorption is a useful therapeutic approach in treatment of metabolic dis- ease, especially diabetes (2). Yet, despite the potential prac- tical utility of this approach, the mechanisms involved remain unclear (3,4). All previous studies that have focused on ways of slowing absorption have achieved this by alterations in major dietary components or the use of pharmacological agents. Although enzyme inhibitors, soluble fibers and foods that produce low glycemic responses, may work partly by delaying absorption, they introduce too many ex- traneous variables to permit clear interpretation of the mech- anism. It is known that differences in protein quantity or type may result in alterations in insulin secretion (5), a-glucosi- dase inhibitors may reduce the total amount of carbohydrate absorbed (6), and fermentation of soluble fiber may influence carbohydrate metabolism secondary to short-chain fatty acid generation (7). We have therefore attempted to clarify this issue by designing a paradigm in which only the rate of nutrient delivery was altered. RESEARCH DESIGN AND METHODS On two separate occasions after an overnight fast, nine healthy male volunteers (aged 37 ± 3 yr, 105 ± 3% ideal body wt; 8) took 50 g glucose in 700 ml of water. On one morning, the drink was consumed in 5 min (bolus), and on another, it was sipped at an even rate of 50 ml/0.25 h over 3.5 h (sipping). The tests were taken in random order. Four hours after the start of glucose ingestion, 100 ml of 5% dex- trose (Baxter Travenol, Deerfield, IL) was given intravenously into a forearm vein over 2 min (intravenous glucose tolerance test [IVGTT]). Previous 5-g IVGTT studies have shown this to raise the blood glucose by ~2 mM and serum insulin by 20 |jiU/ml in healthy subjects (9,10). Venous and capillary blood samples were obtained at 0, 0.5, 1, 2, 3, and 4 h and thereafter at 5-min intervals for the remaining 0.5 h. Complete urine collections over the 4.5-h experimental period were obtained from the last six volunteers. One hundred to 120 ixl of capillary blood was collected into a tube containing From the Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, the Division of Endocrinology and Metabolism, St. Michael's Hos- pital, the Division of Gastroenterology, Toronto General Hospital, Toronto, Ontario, Canada; and the Department of Endocrinology, Royal Post Graduate Medical School, London, England, United Kingdom. Address correspondence and reprint requests to David J.A. Jenkins, De- partment of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario M5S 1A8, Canada. Received for publication 7 August 1989 and accepted in revised form 13 March 1990. DIABETES, VOL. 39, JULY 1990 775 Downloaded from http://diabetesjournals.org/diabetes/article-pdf/39/7/775/357660/39-7-775.pdf by guest on 04 November 2022