Lower Preprandial Insulin and Altered Fuel Use in HIV/Antiretroviral-Exposed Infants in Cameroon

Abstract

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.

Lower mitochondrial DNA and altered mitochondrial fuel metabolism in HIV-exposed uninfected infants in Cameroon

“…As previously described, [13] we used PCA to consolidate and reduce the total number of AC and BCAA metabolites into a smaller number of uncorrelated variables/components. In general, PC1 was comprised of long-chain ACs and free carnitine (C0), PC2 of 3-hydroxy long-chain ACs, PC3 of short-chain and BCAA-related ACs, PC4 of unsaturated medium- and long-chain ACs, PC5 of BCAAs, PC6 of adipoyl/3-methylglutarylcarnitine (C6-DC) and dodecanoylcarnitine (C12) ACs, and PC7 of medium-chain ACs and tetradecenoylcarnitine (C14:1).…”

“…The design of this study has been previously reported. [13] Multiple gestation pregnancies and those ending in spontaneous/therapeutic abortions or intra-uterine fetal demise, as well as infants with HIV infection by positive DNA PCR testing at 6 weeks of life were excluded. During the study period, national guidelines for the Prevention of Mother-To-Child Transmission of HIV (PMTCT) underwent changes, reflecting updated WHO Guidelines.…”

“…The number of components was chosen based on eigenvalues >1, scree plots, and theoretical congruence with prior knowledge of intermediate metabolic pathways as previously described. [13] Principal component (PC) scores were calculated for each infant as a linear combination of the optimally weighted metabolites (based on standardized scoring coefficients) with each PC score representing the level of activity for a particular mitochondrial metabolic pathway. [13] Correlations between each of the PCs and mtDNA ratio were evaluated using Spearman’s correlation.…”

“…[13] Principal component (PC) scores were calculated for each infant as a linear combination of the optimally weighted metabolites (based on standardized scoring coefficients) with each PC score representing the level of activity for a particular mitochondrial metabolic pathway. [13] Correlations between each of the PCs and mtDNA ratio were evaluated using Spearman’s correlation. Lastly, linear regression modeling was applied to assess the association of in utero HIV/ARV plus either postnatal zidovudine or nevirapine with mtDNA content while adjusting for confounders and PCA-derived PC scores of the metabolites.…”

“…[11, 12] Moreover, we have also previously described a signature array of short-chain ACs and BCAAs in association with insulin resistance in HEU infants. [13] Few studies have evaluated mitochondrial DNA (mtDNA) content or the relationship between mtDNA levels and pathways of intermediary metabolism in HEU compared to HIV-unexposed uninfected (HUU) infants in Africa. Given that approximately 20% of the general pediatric population is currently HEU in sub-Saharan Africa, [14] we sought to assess mtDNA content in HEU infants in Cameroon and investigate its relationship with intermediary metabolites.…”