TY - JOUR
T1 - Lower preprandial insulin and altered fuel use in HIV/antiretroviral-exposed infants in Cameroon
AU - Jao, Jennifer
AU - Kirmse, Brian
AU - Yu, Chunli
AU - Qiu, Yunping
AU - Powis, Kathleen
AU - Nshom, Emmanuel
AU - Epie, Fanny
AU - Tih, Pius Muffih
AU - Sperling, Rhoda S.
AU - Abrams, Elaine J.
AU - Geffner, Mitchell E.
AU - Le Roith, Derek
AU - Kurland, Irwin J.
N1 - Publisher Copyright:
Copyright © 2015 by the Endocrine Society.
PY - 2015/9/1
Y1 - 2015/9/1
N2 - 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 withHUUinfants. 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 thanHUUinfants. Future studies are warranted to determine whether observed differences have lasting metabolic implications, such as later insulin resistance.
AB - 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 withHUUinfants. 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 thanHUUinfants. Future studies are warranted to determine whether observed differences have lasting metabolic implications, such as later insulin resistance.
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U2 - 10.1210/JC.2015-2198
DO - 10.1210/JC.2015-2198
M3 - Article
C2 - 26133363
AN - SCOPUS:84941710980
SN - 0021-972X
VL - 100
SP - 3260
EP - 3269
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 9
ER -
