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Objective-To compare the distribution of lipid and glucose abnormalities and altered fat distribution among vertically HIV-infected subjects and controls.Design-Cross-sectional multicenter study in HIV-infected (HIVpos) subjects 7-24 years, stratified by Tanner stage and protease inhibitor (PI) use (PI; N=161 and non-PI; N=79) and seronegative controls (HIVneg; N=146).Methods-Measurements included fasting lipids, glucose, insulin, 2-h oral glucose tolerance test, dual-energy X-ray absorptiometry, anthropometry, and ART and medical histories. Multiple linear regression models were used to compare distributions between HIVpos and HIVneg.Results-Both HIVpos groups had long exposures to ART. PI and non-PI had similar current CD4 count and HIV RNA, but PI had lower nadir CD4, higher peak HIV RNA, and more advanced CDC disease stage. In adjusted analyses, both HIVpos groups had significantly lower mean z-scores for height, weight, BMI, and total and limb fat, compared with HIVneg. Mean triglycerides were significantly higher and HDL cholesterol lower in both HIVpos groups relative to HIVneg. PI also had significantly higher mean total, LDL, and non-HDL cholesterol. Mean fasting insulin was higher in both HIVpos groups, and 2-h glucose and insulin were higher in the PI group. Ritonavir was associated with increasing dyslipidemia and altered glucose metabolism. Author Contributions: GMA and KM designed the study and the analyses, with input from the other authors. JL and DJ had primary responsibility for data analysis. AZ, BH and WM contributed to the collection/analysis of clinical and laboratory data. GMA wrote the first draft of the paper but all authors contributed to writing the paper and approved the final version of the paper.Preliminary results of this study were presented at the 9 th International Workshop on Lipodystrophy and Adverse Drug Reactions in Sydney, Australia, July 2007. Conclusions-In a large group of vertically-infected children/youth with extensive ART exposure, height, weight, and total and limb fat were lower than in controls. There was a high prevalence of lipid abnormalities among those on PI and evidence of developing insulin resistance, factors that may accelerate lifetime risk for cardiovascular disease. NIH Public Access

The parenteral multivitamin preparations that are commercially available in the United States (U.S.) meet the requirements for most patients who receive parenteral nutrition (PN). However, a separate parenteral vitamin D preparation (cholecalciferol or ergocalciferol) should be made available for treatment of patients with vitamin D deficiency unresponsive to oral vitamin D supplementation. Carnitine is commercially available and should be routinely added to neonatal PN formulations. Choline should also be routinely added to adult and pediatric PN formulations; however, a commercially available parenteral product needs to be developed. The parenteral multi–trace element (TE) preparations that are commercially available in the U.S. require significant modifications. Single‐entity trace element products can be used to meet individual patient needs when the multiple‐element products are inappropriate (see Summary/A.S.P.E.N. Recommendations section for details of these proposed modifications).

Carnitine has a critical role in energy metabolism. Many of the functions of carnitine are not clearly elucidated and many of the regulatory mechanisms governing carnitine metabolism are ill-defined. Carnitine deficiency can be life threatening but may be resolved with carnitine supplementation. Various groups of individuals in addition to those with the classical carnitine deficiency syndrome may require exogenous carnitine. Carnitine nutriture can no longer be ignored.

Mitochondria play important roles in human physiological processes, and therefore, their dysfunction can lead to a constellation of metabolic and nonmetabolic abnormalities such as a defect in mitochondrial gene expression, imbalance in fuel and energy homeostasis, impairment in oxidative phosphorylation, enhancement of insulin resistance, and abnormalities in fatty acid metabolism. As a consequence, mitochondrial dysfunction contributes to the pathophysiology of insulin resistance, obesity, diabetes, vascular disease, and chronic heart failure. The increased knowledge on mitochondria and their role in cellular metabolism is providing new evidence that these disorders may benefit from mitochondrial-targeted therapies. We review the current knowledge of the contribution of mitochondrial dysfunction to chronic diseases, the outcomes of experimental studies on mitochondrial-targeted therapies, and explore the potential of metabolic modulators in the treatment of selected chronic conditions. As an example of such modulators, we evaluate the efficacy of the administration of L-carnitine and its analogues acetyl and propionyl L-carnitine in several chronic diseases. L-carnitine is intrinsically involved in mitochondrial metabolism and function as it plays a key role in fatty acid oxidation and energy metabolism. In addition to the transportation of free fatty acids across the inner mitochondrial membrane, L-carnitine modulates their oxidation rate and is involved in the regulation of vital cellular functions such as apoptosis. Thus, L-carnitine and its derivatives show promise in the treatment of chronic conditions and diseases associated with mitochondrial dysfunction but further translational studies are needed to fully explore their potential.