Lower preprandial insulin and altered fuel use in HIV/antiretroviral-exposed infants in Cameroon

Jennifer Jao, Brian Kirmse, Chunli Yu, Yunping Qiu, Kathleen Powis, Emmanuel Nshom, Fanny Epie, Pius Muffih Tih, Rhoda S. Sperling, Elaine J. Abrams, Mitchell E. Geffner, Derek Le Roith, Irwin J. Kurland

Research output: Contribution to journalArticle

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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 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.

Original languageEnglish (US)
Pages (from-to)3260-3269
Number of pages10
JournalJournal of Clinical Endocrinology and Metabolism
Volume100
Issue number9
DOIs
StatePublished - Sep 1 2015

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Cameroon
HIV
Insulin
Nevirapine
Branched Chain Amino Acids
Zidovudine
Metabolites
Linear regression
Metabolism
Principal component analysis
Health
Plasmas
HIV-2
Substrates

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology
  • Biochemistry, medical
  • Endocrinology, Diabetes and Metabolism

Cite this

Lower preprandial insulin and altered fuel use in HIV/antiretroviral-exposed infants in Cameroon. / Jao, Jennifer; Kirmse, Brian; Yu, Chunli; Qiu, Yunping; Powis, Kathleen; Nshom, Emmanuel; Epie, Fanny; Tih, Pius Muffih; Sperling, Rhoda S.; Abrams, Elaine J.; Geffner, Mitchell E.; Le Roith, Derek; Kurland, Irwin J.

In: Journal of Clinical Endocrinology and Metabolism, Vol. 100, No. 9, 01.09.2015, p. 3260-3269.

Research output: Contribution to journalArticle

Jao, J, Kirmse, B, Yu, C, Qiu, Y, Powis, K, Nshom, E, Epie, F, Tih, PM, Sperling, RS, Abrams, EJ, Geffner, ME, Le Roith, D & Kurland, IJ 2015, 'Lower preprandial insulin and altered fuel use in HIV/antiretroviral-exposed infants in Cameroon', Journal of Clinical Endocrinology and Metabolism, vol. 100, no. 9, pp. 3260-3269. https://doi.org/10.1210/JC.2015-2198
Jao, Jennifer ; Kirmse, Brian ; Yu, Chunli ; Qiu, Yunping ; Powis, Kathleen ; Nshom, Emmanuel ; Epie, Fanny ; Tih, Pius Muffih ; Sperling, Rhoda S. ; Abrams, Elaine J. ; Geffner, Mitchell E. ; Le Roith, Derek ; Kurland, Irwin J. / Lower preprandial insulin and altered fuel use in HIV/antiretroviral-exposed infants in Cameroon. In: Journal of Clinical Endocrinology and Metabolism. 2015 ; Vol. 100, No. 9. pp. 3260-3269.
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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.

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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.

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