Metabolic Effects of Reducing Rate of Glucose Ingestion by Single Bolus Versus Continuous Sipping

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.