Lower Preprandial Insulin and Altered Fuel Use in HIV/Antiretroviral-Exposed Infants in Cameroon
Year: 2015
Type: article
Study design: Observational Study
Abstract: CONTEXT: Intrauterine HIV/antiretroviral (ARV) and postnatal ARVs are known to perturb energy metabolism and could have permanent effects on future metabolic health. Such maladaptive effects could be mediated by changes in mitochondrial function and intermediary metabolism due to fetal and early-life ARV exposure in HIV/ARV-exposed uninfected (HEU) infants. OBJECTIVE: The objective of the study was to understand the relationship(s) between mitochondrial fuel use (assessed via acylcarnitines and branched chain amino acids) and preprandial insulin in infants exposed to in utero HIV/ARV plus postnatal zidovudine or nevirapine compared with HIV/ARV-unexposed uninfected (HUU) infants. DESIGN: This was a prospective cohort study with the following three groups: 1) intrauterine HIV/ARV/postnatal zidovudine-exposed (HEU-A), 2) intrauterine HIV/ARV/postnatal nevirapine-exposed (HEU-N), and 3) HUU infants. Principal component analysis and linear regression modeling were performed to assess the association between in utero HIV/ARV exposure and infant insulin. SETTING: The study was conducted at Cameroonian urban antenatal centers. PARTICIPANTS: HIV-infected and -uninfected pregnant woman/infant dyads participated in the study. MAIN OUTCOME: Preprandial insulin was the main outcome measured. RESULTS: Of 366 infants, 38 were HEU-A, 118 HEU-N. Forty intermediary metabolites were consolidated into seven principal components. In a multivariate analysis, both HEU-A (β = -.116, P= .012) and HEU-N (β = -.070, P= .022) demonstrated lower insulin compared with HUU infants. However, at high levels of plasma metabolites, HEU-A (β = .027, P= .050) exhibited higher insulin levels than HEU-N or HUU infants. A unique array of short-chain acylcarnitines (β = .044, P= .001) and branched-chain amino acids (β = .033, P= .012) was associated with insulin. CONCLUSION: HEU-A and HEU-N infants have lower preprandial insulin levels at 6 weeks of age and appear to use metabolic fuel substrates differently than HUU infants. Future studies are warranted to determine whether observed differences have lasting metabolic implications, such as later insulin resistance.
DOI: 10.1210/jc.2015-2198
Institutions: Children's National, George Washington University, New York University, Icahn School of Medicine at Mount Sinai, Albert Einstein College of Medicine, Massachusetts General Hospital, Cameroon Baptist Convention Health Services, Columbia University, University of Southern California, Saban Research Institute
Language: English
Subfield: Emergency Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Strategies to optimize ART services for maternal&child health: the MCH-ART study, Growth Trends and Mortality Risks Among HIV-exposed Infants in Botswana, Metabolic Effects of In Utero Antiretrovirals on HIV Exposed Uninfected Infants, G4295942080, Pediatric HIV/AIDS Cohort Study (PHACS) Coordinating Center (CC) (U01), Stem Cell-Based Therapies for Mitigation of Acute Radiation Syndromes, Clinical and Translational Science Institute at Children's National, Pediatric HIV/AIDS Cohort Study (PHACS): Data and Operations Center (DOC)., Diabetes Research and Training Center, NYR-Diabetes Research Center (NYR-DRC)
OpenAlex ID: W1940137311