The quantification of gluconeogenesis (GNG) by (2)H2O and [2-(13)C]glycerol and the mass isotopomer dilution analysis of glucose does not involve assumptions regarding the enrichment of the oxaloacetate precursor pool. To compare these two methods we measured GNG in six healthy postabsorptive males under identical, strictly standardized, eucaloric conditions, once after oral administration of (2)H2O and once during a primed continuous infusion of [2-(13)C]glycerol. Endogenous glucose production (EGP) was measured by infusion of [6,6-(2)H(2)]glucose. EGP was not different after (2)H2O administration or during [2-(13)C]glycerol infusion (12.2 +/- 0.7 vs. 11.7 +/- 0.3 micromol/kg.min). However, GNG measured after (2)H2O administration was significantly higher than that during [2-(13)C]glycerol infusion (7.4 +/- 0.7 vs. 4.9 +/- 0.6 micromol/kg.min; P = 0.03), representing approximately 60% and 41% of EGP, respectively. The (2)H2O study was repeated during primed continuous infusion of unlabeled glycerol, showing that infusion of glycerol at the rate used in the [2-(13)C]glycerol method does not affect the measurement of GNG with (2)H2O, viz. 7.4 +/- 0.7 without glycerol vs. 7.6 +/- 0.9 micromol/kg.min with glycerol, representing approximately 60% vs. 62% of EGP. In conclusion, GNG measured by (2)H(2)O yields higher results than those measured by [2-(13)C]glycerol. This discrepancy is not merely caused by infusion of glycerol per se. Rather, the discrepancy between both methods probably relates to conceptual problems in underlying assumptions in one or both methods.

Most obese men have hepatic insulin sensitivity within the range of non-obese controls, but below-normal peripheral insulin sensitivity, that is, insulin resistance. Fasting insulin (>74 pmol l(-1) with current insulin immunoassay) may be used for identification of insulin-resistant (or metabolically unhealthy) obese men in research and clinical settings.

Objective: Bariatric surgery has rapid metabolic effects on glucose metabolism before the occurrence of clinically significant weight loss. This suggests an acute effect of the surgery itself, e.g., resulting from bypassing the nutrient flow from the proximal gastrointestinal tract. Rapid effects of Roux-en-Y gastric bypass surgery (RYGB) on glucose metabolism were defined. Design and Methods: Glucose metabolism and total triglyceride hydrolysis in the basal state and during a hyperinsulinemic euglycemic clamp using stable isotopes 2 weeks were studied before and after RYGB. Results: Eighteen pre-menopausal women scheduled for RYGB were included. 2 weeks after RYGB median weight loss was 7.8 kg. Basal insulin and glucose levels decreased after surgery. Endogenous glucose production (EGP) was lower after surgery. In addition, insulin levels were lower during the clamp after surgery, suggesting enhanced clearance. Hepatic and peripheral insulin sensitivity did not change. Free fatty acid (FFA) levels increased after surgery both in the basal state and during the first step of the clamp. Total triglyceride hydrolysis did not change in the basal state and tended to be higher during hyperinsulinemia. Conclusions: Within 2 weeks, RYGB reduces basal EGP as well as insulin and glucose levels without an acute beneficial effect on hepatic or peripheral insulin sensitivity. The latter may be explained by higher rates of lipolysis and exposure to FFA induced by the hypocaloric state.

No abstract