Infections and systemic inflammation are associated with lower plasma concentration of insulin-like growth factor I among Malawian children

Abstract

Background Insulin-like growth factor I (IGF-I) is the most important hormonal promoter of linear growth in infants and young children. Objectives The objectives of this study were to compare plasma IGF-I concentration in a low- compared with a high-income country and characterize biological pathways leading to reduced IGF-I concentration in children in a low-income setting. Methods We analyzed plasma IGF-I concentration from 716 Malawian and 80 Finnish children at 6–36 mo of age. In the Malawian children, we studied the association between IGF-I concentration and their environmental exposures; nutritional status; systemic and intestinal inflammation; malaria parasitemia and viral, bacterial, and parasitic enteric infections; as well as growth at 18 mo of age. We then conducted a pathway analysis to identify direct and indirect associations between these predictors and IGF-I concentration. Results The mean IGF-I concentrations were similar in Malawi and Finland among 6-mo-old infants. At age 18 mo, the mean ± SD concentration was almost double among the Finns compared with the Malawians [24.2 ± 11.3 compared with 12.5 ± 7.7 ng/mL, age- and sex-adjusted difference in mean (95% CI): 11.8 (9.9, 13.7) ng/mL; P < 0.01]. Among 18-mo-old Malawians, plasma IGF-I concentration was inversely associated with systemic inflammation, malaria parasitemia, and intestinal Shigella, Campylobacter, and enterovirus infection and positively associated with the children's weight-for-length z score (WLZ), female sex, maternal height, mother's education, and dry season. Seasonally, mean plasma IGF-I concentration was highest in June and July and lowest in December and January, coinciding with changes in children's length gain and preceded by ∼2 mo by the changes in their WLZ. Conclusions The mean plasma IGF-I concentrations are similar in Malawi and Finland among 6-mo-old infants. Thereafter, mean concentrations rise markedly in Finland but not in Malawi. Systemic inflammation and clinically nonapparent infections are strongly associated with lower plasma IGF-I concentrations in Malawi through direct and indirect pathways.

The synergistic interaction of systemic inflammation, dysbiosis and antimicrobial resistance promotes growth restriction in children with acute severe malnutrition: An emphasis on Escherichia coli

“…This statement is supported by a Kenyan study with HIV-positive SAM children responding to feeding therapy, which showed an average height increase of 0.34 mm/day over 60 days of follow-up, but demonstrated a negative correlation between the systemic inflammatory markers IL-2, IL-17a, and LBP with their growth (Njunge et al, 2020). Additionally, Maleta K. et al reported, in 2021, a comparison between 716 Malawian and 80 Finnish children and found that at 18 months old, Malawian children had almost half the concentration of IGF-1 of that found in Finns (Maleta et al, 2021). They also reported a strong relationship of low plasmatic IGF-1 levels with the systemic inflammatory marker CRP in a dose-dependent way, and with intestinal infection by Campylobacter or Shigella bacteria (Maleta et al, 2021).…”

“…Additionally, Maleta K. et al reported, in 2021, a comparison between 716 Malawian and 80 Finnish children and found that at 18 months old, Malawian children had almost half the concentration of IGF-1 of that found in Finns (Maleta et al, 2021). They also reported a strong relationship of low plasmatic IGF-1 levels with the systemic inflammatory marker CRP in a dose-dependent way, and with intestinal infection by Campylobacter or Shigella bacteria (Maleta et al, 2021). Despite the fact that it has not been clinically evaluated in SAM children, an experimental work performed in dogs inoculated with E. coli-derived LPS has shown an important decrease in IGF-1 levels, as well as in the anti-diabetic hormone adiponectin (Tvarijonaviciute et al, 2011), suggesting that infection with this bacterium potentially could limit growth while promoting diabetes in affected children.…”

Association between asymptomatic infections and linear growth in 18–24‐month‐old Malawian children

“…We chose this age interval as it is a period when infections are common (Fan et al, 2019;MAL-ED Network Investigators, 2017;Platts-Mills et al, 2015) and growth faltering still continues (Espo et al, 2002;Maleta et al, 2020;Victora et al, 2010) among children in low-income countries.…”

“…One such exposure is systemic inflammation, which can block IGF‐1 synthesis in the liver (Walters & Griffiths, 2009 ). Inflammation is often caused by infections, and both symptomatic and asymptomatic infections have been associated with reduced plasma concentrations of IGF‐1 among infants and young children in low‐income settings (DeBoer et al, 2017 ; Maleta et al, 2020 ; Prendergast et al, 2014 ; Syed et al, 2018 ).…”

IGF-1 and IGFBP-3 in Inflammatory Cachexia

“…On the other hand, in chronic inflammatory conditions, such as experimental arthritis, plasma concentrations of IGF-1 and GH as well as pituitary GH mRNA are decreased [2,7,8]. In children with cystic fibrosis, juvenile idiopathic arthritis, or inflammatory bowel diseases, an alteration in both GH and IGF-1 secretion has also been observed, together with growth retardation [9,10]. Furthermore, critically ill patients during the acute phase of the illness have an increase in GH with a decrease in IGF-1 and in the main plasma IGF-1 binding protein-3 (IGFBP-3).…”