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Session 34 Oral Abstract Session Late Breakers II Session Time: Thursday, 9:30 am - 11:45 am Room 4B

10:15   LB12. Analysis of Gluconeogenesis Using Stable Isotopes in Patients with HIV B. C. Weis1, D. Margolis*1&2, M. E. Merritt1, S. C. Burgess1, and C. R. Malloy1&2 1Univ. of Texas Southwestern Med. Ctr., Dallas and 2Dallas Veterans Affairs Med. Ctr., TX Background: There is increasing awareness of HIV-related metabolic disorders, including hypertriglyceridemia. Classical methods using intravenous radiotracers for measuring metabolism are not practical for outpatient studies. Recently, nuclear magnetic resonance (NMR) methods have been introduced for analysis of gluconeogenesis using stable isotopes. This study was designed with 2 objectives: to demonstrate an outpatient protocol using oral isotopes and NMR analysis of serum glucose and to quantify the glycerol contribution to the pool of gluconeogenic precursors in the liver. Methods: All subjects enrolled were HIV-positive and on therapy including at least 1 protease inhibitor. Criteria for admission into the lipoatrophy group was the observation of marked facial and peripheral adipose wasting. The control group did not show similar changes. At 0700 after an overnight fast, subjects received oral deuterium oxide (5 g/kg body water) and 13C-labeled propionate (10 mg/kg body weight). Blood (30 mL) was drawn 4 hours later. Plasma glucose was derivatized for proton-decoupled 2H- and 13C-NMR spectroscopy. Results: 5 subjects with HIV and lipoatrophy were compared to 5 age-and gender-matched subjects with HIV but no evident lipoatrophy. Based on the deuterium NMR spectra of control patients, glucose released by the liver originated from glycogen (39±17%), glycerol( 7.9±7.2%), and the citric acid cycle (53.8±10%). Among lipoatrophy patients, hepatic glucose production was derived from glycogen (45.2±10%), glycerol (19.6±5.8%), and the citric acid cycle (35.3±10.6%). The carbon spectra confirmed significant flux from the TCA cycle into glucose production. The fractional contribution of glycogen to hepatic glucose production was not different between the 2 groups, but relative gluconeogenesis from glycerol was increased among patients with lipoatrophy (p <0.05). Conclusions: After administration of oral 2H- and 13C-enriched tracers, NMR spectra of plasma glucose provides an efficient method of assessing relative fluxes in key pathways involved in gluconeogenesis. In a small number of HIV-positive patients, the physical findings of lipoatrophy were associated with an increased fractional contribution of glycerol to hepatic gluconeogenesis after an overnight fast.

©2002 9th Conference on Retroviruses and Opportunistic Infections