We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment.

BackgroundHIV infection occurs in 30% of children with severe acute malnutrition in sub-Saharan Africa. Effects of HIV on the pathophysiology and recovery from malnutrition are poorly understood.MethodsWe conducted a prospective cohort study of 75 severely malnourished Ugandan children. HIV status/CD4 counts were assessed at baseline; auxologic data and blood samples were obtained at admission and after 14 days of inpatient treatment. We utilized metabolomic profiling to characterize effects of HIV infection on metabolic status and subsequent responses to nutritional therapy.FindingsAt admission, patients (mean age 16.3 mo) had growth failure (mean W/H z-score −4.27 in non-edematous patients) that improved with formula feeding (mean increase 1.00). 24% (18/75) were HIV-infected. Nine children died within the first 14 days of hospitalization; mortality was higher for HIV-infected patients (33% v. 5%, OR = 8.83). HIV-infected and HIV-negative children presented with elevated NEFA, ketones, and even-numbered acylcarnitines and reductions in albumin and amino acids. Leptin, adiponectin, insulin, and IGF-1 levels were low while growth hormone, cortisol, and ghrelin levels were high. At baseline, HIV-infected patients had higher triglycerides, ketones, and even-chain acylcarnitines and lower leptin and adiponectin levels than HIV-negative patients. Leptin levels rose in all patients following nutritional intervention, but adiponectin levels remained depressed in HIV-infected children. Baseline hypoleptinemia and hypoadiponectinemia were associated with increased mortality.ConclusionsOur findings suggest a critical interplay between HIV infection and adipose tissue storage and function in the adaptation to malnutrition. Hypoleptinemia and hypoadiponectinemia may contribute to high mortality rates among malnourished, HIV-infected children.

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IntroductionSuboptimal diet and physical inactivity downgrade the putative benefits of Antiretroviral Therapy (ART) among People Living with HIV (PLWH). However, there is paucity of literature on dietary intake and cardiometabolic profiles of PLWH in Uganda.MethodsA cross-sectional study among PLWH in Uganda was conducted. Dietary intake was assessed using a 24h recall method of 2 non-consecutive days. The short International Physical Activity Questionnaire assessed participants' physical activity. Fasted blood samples were analyzed for Fasting Blood Glucose (FBG), total cholesterol, LDL-c, HDL-c and triglycerides. Blood pressure and anthropometric measurements were performed following step 2 of the WHO STEPS.Results253 patients completed in this study. A high prevalence of low HDL-c (31.9%), abdominal obesity (44.5%), high BMI (51.6%), raised FBG (45.3%), high SBP (31.5%), elevated triglycerides (26.4%) and metabolic syndrome (28%) was found. More women were identified with metabolic syndrome (31.5%) than men (19.2%). Low prevalence of high LDL-c (4.7%) and total cholesterol (9.8%) was found. Diets had a high carbohydrate (65.8 ± 10.4) E% and fiber intake (30.1 ± 12.7) g with minimal PUFA (6.1 ± 2.3) E%, fruits and vegetables (1.4 servings). High proportions were found of unmet intake for vitamin A (38.2%), B1(48.8%), B2 (29.6%), B12 (29%), folate (61.4%), Ca (76%), Zn (53.1%) and Mg (41.7%). Mean MET min was 6,700 ± 5,509 and over 68% of the participants had >3,000 MET min.ConclusionOur findings reveal a high prevalence of metabolic disturbances among PLWH in Uganda and further highlight that their diets are suboptimal with low fruits and vegetable intake