Hellerstein MK, Neese R, Papageorgopoulos C, Hoh R; International Conference on AIDS.
Int Conf AIDS. 1996 Jul 7-12; 11: 332 (abstract no. Tu.B.2387).
University of California, Berkeley, CA. Fax: 510-642-0535. E-mail: march@nature.berkeley.edu.
Objective: We measured several kinetic processes in men with AWS and normal controls, using stable isotope/mass spectrometric techniques. Methods: Processes included lipolysis, hepatic de novo lipogenesis (DNL) and cholesterol (C) synthesis; hepatic glucose production, pathways of glycogen synthesis, and gluconeogenesis (GNG), by dilution or mass isotopomer methods. Kinetic processes were compared to soluble TNF receptor I and II, IGF-1, triglycerides and lean body mass (LBM) response to nutritional supplementation. Results: Compared to HIV-negative controls (Ctrls), abnormalities of mean values in AWS were observed for lipolysis (n = 18) (25% elevated), resting energy expenditure (n = 115) (13% increased), substrate cycling (n = 15) (elevated, but thermogenically insignificant at less than 20kCal/day); DNL (n = 73) (markedly increased, especially in fed state, but highly variable among subjects and not accounting for body composition differences quantitively); C synthesis (n = 25) (increased, despite low serum C, indicating increased losses not reduced synthesis); glucose production (n = 28) (slightly increased in a subset but normally suppressable by iv glucose); direct glycogen synthesis pathway (n = 12) (reduced rather than increased, excluding surplus hepatic glucose balance is not as explanation for increased DNL); GNG (n = 17) (increased in subset, perhaps representing a nitrogen-depleting process). Increased DNL or other kinetic abnormalities did not correlate with TNF RI or II, TNF levels, IGF-1, C synthesis, Peripheral blood mononuclear cell cytokine release, triglyceride or cholesterol concentrations. Increased DNL was the most useful metabolic parameter for prediction of LBM response to nutrients (higher DNL, worse LBM response, r2 = 0.46). Conclusions: We conclude that, (1) The pattern of lipid and CHO abnormalities is most consistent with cytokine effects rather than dietary effects (more increased DNL in fed state than fasted, as observed for TNF and glycogen stores in animals; increased C synthesis, GNG, lipolysis; reduced direct pathway); (2) Circulating cytokines are not useful measurements; (3) DNL is a useful prognostic measure, presumably by reflecting cytokine presence; (4) These metabolic changes do not explain altered body composition or energy expenditure quantitatively but by reflecting underlying metabolic abnormality; (5) Marked inter-individual variability may reflect pathogenic heterogeneity for AWS and prove useful in patient stratification.
Publication Types:
Keywords:
- Abnormalities, Multiple
- Body Composition
- Diet
- Diet, Fat-Restricted
- Energy Metabolism
- Fasting
- Gluconeogenesis
- Glucose
- HIV Wasting Syndrome
- Humans
- Lipids
- Lipolysis
- Male
- Triglycerides
- abnormalities
- metabolism
Other ID:
UI: 102218488
From Meeting Abstracts