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Title: Determinants of intramyocellular lipid accumulation in early childhood
Authors: Michael N
Gupta V
Sadananthan SA 
Sampathkumar A 
Chen L
Pan H
Tint MT 
Lee KJ
Loy SL 
Aris IM 
Shek LP 
Yap FKP 
Godfrey KM
Leow MK 
Lee YS 
Kramer MS 
Henry CJ 
Fortier MV 
Seng Chong Y 
Gluckman PD 
Karnani N 
Velan SS 
Issue Date: 28-Aug-2019
Publisher: Nature Publishing Group
Citation: Michael N, Gupta V, Sadananthan SA, Sampathkumar A, Chen L, Pan H, Tint MT, Lee KJ, Loy SL, Aris IM, Shek LP, Yap FKP, Godfrey KM, Leow MK, Lee YS, Kramer MS, Henry CJ, Fortier MV, Seng Chong Y, Gluckman PD, Karnani N, Velan SS (2019-08-28). Determinants of intramyocellular lipid accumulation in early childhood. International Journal of Obesity. ScholarBank@NUS Repository.
Abstract: Background/Objectives: Accumulation of lipid droplets inside skeletal muscle fibers (intramyocellular lipids or IMCL) with increasing obesity has been linked to skeletal muscle insulin resistance and risk of type 2 diabetes in both adults and prepubertal children. We aimed to evaluate the associations of race, genotype, prenatal factors, and postnatal factors with IMCL in early childhood. Subjects/Methods: This study was a secondary analysis performed on the GUSTO birth cohort. Soleus muscle IMCL of 392 children at 4.5 years of age was measured by magnetic resonance spectroscopy, of which usable imaging data were obtained from 277 children (137 Chinese, 87 Malays, and 53 Indians). Metabolic assessments (fasting glucose, insulin, and HOMA-IR) were performed at age 6. Results: The mean IMCL level at 4.5y was 0.481 ± 0.279% of water resonance (mean ± sd). Corroborating with results from adults, Indian children had the highest IMCL levels compared with Malay and Chinese children. Among the prenatal factors, the rate of gestational weight gain (GWG rate) was associated with offspring IMCL (B= 0.396(0.069, 0.724); p=0.018). Both race and GWG rate continued to be associated with offspring IMCL even after accounting for current offspring BMI. Postnatally, IMCL was associated with shorter breastfeeding duration (B= 0.065 0.001, 0.128) p=0.045) and conditional relative weight gain between ages 2 and 3 (B= 0.052(0.012, 0.093); p=0.012). The associations with postnatal factors were attenuated after adjusting for current offspring BMI. IMCL was positively associated with offspring BMI (B=0.028 (0.012, 0.044); p=0.001). IMCL levels were not associated with fasting glucose, fasting insulin, and HOMA-IR at age 6. Conclusion: This study provides evidence that IMCL accumulation occurs in early childhood and that developmental factors and race are associated with it. We also show that early childhood IMCL accumulation is well tolerated, suggesting that the adverse associations between IMCL and insulin resistance may emerge at older ages.
Source Title: International Journal of Obesity
ISSN: 03070565
DOI: 10.1038/s41366-019-0435-8
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