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Infections and systemic inflammation are associated with lower plasma concentration of insulin-like growth factor I
Kenneth Maleta1, Yue-Mei Fan2, Juho Luoma2
1School of Public Health and Family Medicine, College of Medicine, University of Malawi, Blantyre, Malawi.
Insights
Plasma insulin-like growth factor I (IGF-I) concentrations are similar in Malawian and Finnish infants at 6 months. By 18 months, Finnish children have significantly higher IGF-I, linked to inflammation and infections in Malawi.
Area of Science:
- Pediatric endocrinology
- Global child health
- Nutritional science
Background:
- Insulin-like growth factor I (IGF-I) is a key hormone for linear growth in young children.
- Disparities in childhood growth are observed between high- and low-income countries.
Purpose of the Study:
- Compare plasma IGF-I concentrations in Malawian (low-income) and Finnish (high-income) children.
- Identify biological pathways contributing to reduced IGF-I in low-income settings.
Main Methods:
- Analyzed plasma IGF-I in 716 Malawian and 80 Finnish children (6-36 months).
- Assessed associations between IGF-I and environmental, nutritional, inflammatory, infectious, and growth parameters in Malawian children.
- Utilized pathway analysis to determine direct and indirect relationships.
Main Results:
- Plasma IGF-I levels were similar at 6 months but significantly lower in 18-month-old Malawian children compared to Finnish children.
- In Malawian children, lower IGF-I correlated with systemic inflammation, malaria, and specific enteric infections (Shigella, Campylobacter, enterovirus).
- Higher IGF-I was associated with better weight-for-length z-score, female sex, maternal height, maternal education, and dry season.
Conclusions:
- While initial IGF-I levels are comparable, marked divergence occurs by 18 months, with Finnish children showing higher concentrations.
- Systemic inflammation and subclinical infections are strongly implicated in reduced IGF-I levels in Malawian children via direct and indirect mechanisms.
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.
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