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1 Division of Endocrinology/Diabetes/Metabolism and the General Clinical Research Center, Temple University Hospital, Philadelphia, Pennsylvania 19140; and the 2 Department of Surgery, University of Medicine and Dentistry of New Jersey, School of Osteopathic Medicine, Stratford, New Jersey 08084
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 2H2O method by use of both the C5-to-C2
ratio (C5/C2, with gas chromatography-mass spectrometry) and the
C5-to-2H2O ratio
(C5/2H2O, with isotope ratio mass
spectrometry), and EGP was measured with 3-[3H]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 2H2O by using either C5/C2 or
C5/2H2O; 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 µmol · kg
1 · min1 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.
endogenous glucose production; insulin resistance; prehepatic insulin secretion; deuterated water method
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