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Determinants of intramyocellular lipid accumulation in early childhood
Navin Michael1, Varsha Gupta1, Suresh Anand Sadananthan1
1Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore, Singapore.
Insights
Intramyocellular lipids (IMCL) accumulate in early childhood, influenced by race and developmental factors like gestational weight gain. Early IMCL accumulation appears well-tolerated, with insulin resistance risks potentially emerging later in life.
Area of Science:
- Pediatric Endocrinology
- Metabolic Health
- Human Physiology
Background:
- Intramyocellular lipids (IMCL) accumulation in skeletal muscle is linked to insulin resistance and type 2 diabetes risk in adults and children.
- Understanding early childhood IMCL development is crucial for identifying potential metabolic disease risks.
- Factors influencing IMCL in early life, such as race and developmental influences, require further investigation.
Purpose of the Study:
- To investigate the associations between race, genetic factors, prenatal, and postnatal influences on intramyocellular lipid (IMCL) levels in early childhood.
- To evaluate the relationship between IMCL accumulation and metabolic markers in young children.
Main Methods:
- Secondary analysis of the GUSTO birth cohort, measuring soleus muscle IMCL in 277 children aged 4.5 years using magnetic resonance spectroscopy.
- Assessment of metabolic parameters including fasting glucose, insulin, and HOMA-IR at age 6.
- Statistical analysis to determine associations between IMCL, race, gestational weight gain, breastfeeding duration, relative weight gain, and BMI.
Main Results:
- Indian children exhibited higher IMCL levels compared to Malay and Chinese children.
- Prenatal gestational weight gain rate was associated with offspring IMCL, independent of offspring BMI.
- Postnatal factors like shorter breastfeeding duration and conditional relative weight gain were associated with IMCL, but these associations were attenuated by offspring BMI. IMCL was positively associated with offspring BMI but not with fasting glucose, insulin, or HOMA-IR at age 6.
Conclusions:
- Intramyocellular lipid (IMCL) accumulation occurs in early childhood and is associated with race and developmental factors.
- Early childhood IMCL accumulation is well-tolerated and does not appear to be associated with insulin resistance at age 6.
- Adverse associations between IMCL and insulin resistance may manifest at older ages, warranting further longitudinal studies.
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 4.5 years 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.
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