Non-invasive tracing of liver intermediary metabolism in normal subjects and in moderately hyperglycaemic NIDDM subjects. Evidence against increased gluconeogenesis and hepatic fatty acid oxidation in NIDDM

To lest whether gluconeogencsis is increased in non-insulin-dependent diabetic (NIDDM) patients we infused (post-absorptive stale) healthy subjects and NIDDM patients with [6,6-H-2(2)]glucose (150 min) and (3-[C-13]lactate (6 h), Liver glutamine was sampled with phenylacetate and its labelling pattern determined (mass spectrometry) after purification of the glutamine moiety of urinary-phenylacetyl-glutamine, After correction for (CO2)-C-13 re-incorporation (control test with (NaHCO3)-C-13 infusion) this pattern was used to calculate the dilution factor (F) in the hepatic oxaloacetate pool and fluxes through liver Krebs cycle. NIDDM patients had increased lactate turnover rates (16.18 +/- 0.92 vs 12.14 +/- 0.60 mu mol.kg(-1).min(-1), p < 0.01) and a moderate rise in glucose production (EGP) (15.39 +/- 0.87 vs 12.52 +/- 0.28 mu mol.kg(-1).min(-1), p = 0.047), Uncorrected contributions of gluconeogenesis to EGP were 31 +/- 3 % (control subjects) and 17 +/- 2 % (NIDDM patients), F was comparable (1.34 +/- 0.02 and 1.39 +/- 0.09, respectively) and the corrected percent and absolute contributions of gluconeogenesis were not increased in NIDDM (25 +/- 3 % and 3.8 +/- 0.5 mu mol.kg(-1).min(-1)) compared to control subjects (41 +/- 3 % and 5.1 +/- 0.4 mu mol.kg(-1).min(-1)). The calculated pyruvate carboxylase over pyruvate dehydrogenase activity ratio was comparable (12.1 +/- 2.6 vs 11.2 +/- 1.4), Lastly hepatic fatty oxidation, as estimated by the model, was not increased in NIDDM (1.8 +/- 0.4 vs 1.6 +/- 0.1 mu mol.kg(-1).min(-1)), In conclusion, in the patients studied we found net evidence of increased hepatic fatty oxidation, or, despite the increased lactate turnover rate, an increased gluconeogenesis.