title: Lower Preprandial Insulin and Altered Fuel Use in HIV/Antiretroviral-Exposed Infants in Cameroon.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  The study was conducted at Cameroonian urban antenatal centers.
  
  
  METHODS
  HIV-infected and -uninfected pregnant woman/infant dyads participated in the study.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Jao
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Brian
authors.initials: B
authors.lastname: Kirmse
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Chunli
authors.initials: C
authors.lastname: Yu
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Yunping
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Powis
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Nshom
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Fanny
authors.initials: F
authors.lastname: Epie
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Pius Muffih
authors.initials: PM
authors.lastname: Tih
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Rhoda S
authors.initials: RS
authors.lastname: Sperling
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Elaine J
authors.initials: EJ
authors.lastname: Abrams
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Mitchell E
authors.initials: ME
authors.lastname: Geffner
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Derek
authors.initials: D
authors.lastname: LeRoith
authors.affiliation: Departments of Medicine (J.J.), Obstetrics, Gynecology, and Reproductive Science (J.J.), Genetics and Genomic Sciences (C.Y.), and Obstetrics, Gynecology, and Reproductive Science (R.S.S.), and Department of Medicine (D.L.), Division of Endocrinology, Icahn School of Medicine, Mt Sinai, New York, New York 10029; Department of Pediatrics (B.K.), Division of Genetics and Metabolism, Children's National Medical Center/George Washington University School of Medicine, Washington, DC 20037; Department of Medicine (Y.Q., I.J.K.), Division of Endocrinology, Albert Einstein College of Medicine, Bronx, New York 10461; Departments of Pediatrics and Internal Medicine (K.P.), Massachusetts General Hospital, Boston, Massachusetts 02114; Cameroon Baptist Convention Health Services (E.N., F.E., P.M.T.), Bamenda, Cameroon; ICAP (E.J.A.), Mailman School of Public Health and College of Physicians and Surgeons, Columbia University, New York, New York 10032; and The Saban Research Institute of Children's Hospital Los Angeles (M.E.G.), Keck School of Medicine of University of Southern California, Los Angeles, California 90033.
authors.forename: Irwin J
authors.initials: IJ
authors.lastname: Kurland
mesh_terms: D000597:Amino Acids, Branched-Chain / Q000097:blood; D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002163:Cameroon; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000378:metabolism*; D006801:Humans; D007223:Infant; D007328:Insulin / Q000097:blood*; D008297:Male; D019829:Nevirapine / Q000494:pharmacology* / Q000627:therapeutic use; D011247:Pregnancy; D011446:Prospective Studies; D015215:Zidovudine / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000597:Amino Acids, Branched-Chain; D044966:Anti-Retroviral Agents; D007328:Insulin; D015215:Zidovudine; D019829:Nevirapine