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. 2021 Feb 2;113(2):380-390.
doi: 10.1093/ajcn/nqaa327.

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

Kenneth Maleta  1 , Yue-Mei Fan  2 , Juho Luoma  2 , Ulla Ashorn  2 , Jaden Bendabenda  1 , Kathryn G Dewey  3 , Heikki Hyöty  4   5 , Mikael Knip  2   6   7   8 , Emma Kortekangas  2 , Kirsi-Maarit Lehto  2 , Andrew Matchado  1 , Minyanga Nkhoma  2 , Noora Nurminen  4 , Seppo Parkkila  5   9 , Sami Purmonen  9 , Riitta Veijola  10 , Sami Oikarinen  4 , Per Ashorn  2   11
Affiliations

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

Kenneth Maleta et al. Am J Clin Nutr. .

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.

Keywords: childhood growth faltering; hormonal regulation; infection; pathway analysis; stunting; systemic inflammation.

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Figures

FIGURE 1
FIGURE 1
The distribution of plasma IGF-I concentration among Finnish and Malawian infants and children aged 6–36 mo (FI: n = 78, 79, 62, and 63 at 6, 18, 24, and 36 mo, respectively; MW: n = 520, 606, and 580 at 6, 18, and 30 mo, respectively). At age 18 mo, the age- and sex-adjusted difference in the mean plasma IGF-I concentration between Finnish and Malawian children was 11.8 ng/mL (95% CI: 9.9, 13.7 ng/mL; P < 0.01). Student's t test was used to detect differences between groups. FI, Finnish; IGF-I, insulin-like growth factor I; MW, Malawian.
FIGURE 2
FIGURE 2
The association between plasma IGF-I concentration and length-for-age and weight-for-length z scores at age 18 mo among Malawian children (n = 604). Correlation analysis was used to quantify the relation between each pair of variables. IGF-I, insulin-like growth factor I.
FIGURE 3
FIGURE 3
Seasonal variation among Malawian children in plasma IGF-I concentration and standardized monthly change in their WLZ and LAZ at age 18 mo (n = 605). The monthly change in WLZ and LAZ was calculated using linear models to obtain an estimate. The estimates were standardized for the relative monthly changes in z scores, and seasonal fluctuation during the year was illustrated by using locally weighted scatterplot smoothing. IGF-I, insulin-like growth factor I; LAZ, length-for-age z score; WLZ, weight-for-length z score.
FIGURE 4
FIGURE 4
Pathway model for the determinants of plasma IGF-I concentration among Malawian children aged 18 mo. Red lines indicate negative associations, and blue lines indicate positive associations. The hypothesized causal relations between direct and indirect predictors and plasma IGF-I concentration were analyzed with SEM and GSEM. AGP, α1-acid glycoprotein; GSEM, generalized structural equation modeling; IGF-I, insulin-like growth factor I; SEM, structural equation modeling.
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