Contribution of Abnormal Muscle and Liver Glucose Metabolism to Postprandial Hyperglycemia in NIDDM

Abstract

To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with [¹⁴C]glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O₂, and CO₂ (with forearm calorimetry). In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (R_a) and disappearance (R_d), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1–1.5 h after glucose ingestion, plasma glucose increased by ∼8 mM in NIDDM vs. ∼3 mM in nondiabetic subjects (P < 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects (45.1 ± 2.3 vs. 34.4 ± 1.5 g, P < 0.01), but glucose Rd was not significantly different in NIDDM (35.1 ± 2.4 g) and nondiabetic (33.3 ± 2.7 g) subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 ± 1.1 vs. 6.8 ± 1.0 g, P < 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 ± 1.5 vs. 27.5 ± 0.9 g, P < 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 ± 3.5 vs. 41.0 ± 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 ± 1.0 vs. 5.2 ± 0.3 g in nondiabetic subjects, P < 0.01), and less was stored (11.7 ± 1.3 vs. 16.9 ± 1.5 g, P < 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM.