title: Gluconeogenesis in moderately and severely hyperglycemic patients with type 2 diabetes mellitus.
abstract: We tested the generally accepted concept that increased gluconeogenesis (GNG) and endogenous glucose production (EGP) are the main reasons for postabsorptive hyperglycemia in patients with type 2 diabetes mellitus (T2DM). GNG was measured with the (2)H(2)O method by use of both the C5-to-C2 ratio (C5/C2, with gas chromatography-mass spectrometry) and the C5-to-(2)H(2)O ratio (C5/(2)H(2)O, with isotope ratio mass spectrometry), and EGP was measured with 3-[(3)H]glucose in 27 patients with T2DM [13 with fasting plasma glucose (FPG) >10 mM and 14 with FPG <10 mM] and in 7 weight- and age-matched nondiabetic controls. The results showed 1) that GNG could be determined accurately with (2)H(2)O by using either C5/C2 or C5/(2)H(2)O; 2) that whereas after an overnight fast of 16 h, GNG was higher in the entire group of patients with T2DM than in controls (6.4 vs. 5.0 micromol. kg(-1). min(-1) or 60.4 vs. 51.4% of EGP, P < 0.02), GNG was within normal limits (less than the mean +/- 2 SD of controls or <65.3%) in 11/14 (79%) patients with mild to moderate hyperglycemia (FPG <10 mM) and in 5/13 (38%) of patients with severe hyperglycemia (FPG 10-20 mM); 3) that elevated GNG in T2DM was associated with a 43% decrease in prehepatic insulin secretion, i.e., with hepatic insulin deficiency; and 4) that FPG correlated significantly with glucose clearance (insulin resistance) (r = 0.70) and with GNG (r = 0.50) or EGP (r = 0.45). We conclude 1) that peripheral insulin resistance is at least as important as GNG (and EGP) as a cause of postabsorptive hyperglycemia in T2DM and 2) that GNG and EGP in T2DM are increased under conditions of significant hepatic insulin deficiency and thus probably represent a late event in the course of T2DM.
authors: Division of Endocrinology/Diabetes/Metabolism, Temple University Hospital, Philadelphia, Pennsylvania 19140, USA. bodengh@tuhs.temple.edu
authors: G
authors: G
authors: Boden
authors: X
authors: X
authors: Chen
authors: T P
authors: TP
authors: Stein
mesh_terms: D000368:Aged; D001786:Blood Glucose / Q000096:biosynthesis; D003903:Deuterium; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D005215:Fasting / Q000502:physiology; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005934:Glucagon / Q000097:blood; D005943:Gluconeogenesis / Q000502:physiology*; D005947:Glucose / Q000493:pharmacokinetics; D006019:Glycolysis / Q000502:physiology; D019382:Human Growth Hormone / Q000097:blood; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D006943:Hyperglycemia / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology; D000078790:Insulin Secretion; D007657:Ketone Bodies / Q000097:blood; D008297:Male; D008875:Middle Aged; D014316:Tritium
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D007657:Ketone Bodies; D014316:Tritium; D019382:Human Growth Hormone; D005934:Glucagon; D003903:Deuterium; D005947:Glucose; D006854:Hydrocortisone