Mechanisms for abnormal postprandial glucose metabolism in type 2 diabetes.
To assess mechanisms for postprandial hyperglycemia, we used a triple-isotope technique ([\3-(3)H]glucose and [(14)C]bicarbonate and oral [6,6-dideutero]glucose iv) and indirect calorimetry to compare components of glucose release and pathways for glucose disposal in 26 subjects with type 2 diabetes and 15 age-, weight-, and sex-matched normal volunteers after a standard meal. The results were as follows: 1) diabetic subjects had greater postprandial glucose release (P<0.001) because of both increased endogenous and meal-glucose release; 2) the greater endogenous glucose release (P<0.001) was due to increased gluconeogenesis (P<0.001) and glycogenolysis (P=0.01); 3) overall tissue glucose uptake, glycolysis, and storage were comparable in both groups (P>0.3); 4) glucose clearance (P<0.001) and oxidation (P=0.004) were reduced, whereas nonoxidative glycolysis was increased (P=0.04); and 5) net splanchnic glucose storage was reduced by approximately 45% (P=0.008) because of increased glycogen cycling (P=0.03). Thus in type 2 diabetes, postprandial hyperglycemia is primarily due to increased glucose release; hyperglycemia overcomes the effects of impaired insulin secretion and sensitivity on glucose transport, but intracellular defects persist so that pathways of glucose metabolism are abnormal and glucose is shunted away from normal sites of storage (e.g., liver and muscle) into other tissues.
Woerle
Hans J
HJ
Department of Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Szoke
Ervin
E
Meyer
Christian
C
Dostou
Jean M
JM
Wittlin
Steven D
SD
Gosmanov
Niyaz R
NR
Welle
Stephen L
SL
Gerich
John E
JE
D000409:Alanine / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D005990:Glycerol / Q000097:blood; D050261:Glycogenolysis / Q000502:physiology; D006019:Glycolysis / Q000502:physiology; D006801:Humans; D006943:Hyperglycemia / Q000097:blood / Q000378:metabolism; D007328:Insulin / Q000097:blood; D019344:Lactic Acid / Q000097:blood; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction; D019518:Postprandial Period / Q000502:physiology*; D014781:Viscera / Q000378:metabolism; D014867:Water / Q000378:metabolism
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D014867:Water; D002245:Carbon Dioxide; D019344:Lactic Acid; D005934:Glucagon; D005947:Glucose; D000409:Alanine; D005990:Glycerol