Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM.
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 (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 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 less than 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 less than 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 less than 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 less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 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.
Mitrakou
A
A
Department of Medicine, University of Pittsburgh School of Medicine, PA.
Kelley
D
D
Veneman
T
T
Jenssen
T
T
Pangburn
T
T
Reilly
J
J
Gerich
J
J
D000284:Administration, Oral; D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000032:analysis; D002245:Carbon Dioxide / Q000097:blood; D002250:Carbon Radioisotopes; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000008:administration & dosage / Q000378:metabolism*; D006801:Humans; D006943:Hyperglycemia / Q000209:etiology / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007773:Lactates / Q000097:blood; D008099:Liver / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009132:Muscles / Q000378:metabolism*; D010100:Oxygen / Q000097:blood; D013997:Time Factors
D001786:Blood Glucose; D002250:Carbon Radioisotopes; D007328:Insulin; D007773:Lactates; D002245:Carbon Dioxide; D005947:Glucose; D000409:Alanine; D010100:Oxygen