This pilot study demonstrates that noninvasive assessment of liver lipid by 1
H-MRS is feasible in healthy, normal and overweight prepubertal children and highlights the methodology of 1
H-MRS in a standard pediatric clinical environment. Most notably, our preliminary results are the first to demonstrate in exclusively prepubertal, healthy children who are both normal and overweight that many of the relations between IHL and components of the metabolic syndrome in adults and adolescents6–9,11,12
are also present in normal and overweight, apparently healthy prepubertal children. For instance, children with higher BMI and total adiposity and larger waist circumferences had increased IHL stores. Increased IHL stores, in turn, were significantly correlated with lactate dehydrogenase, a nonspecific marker of tissue damage (including liver).
Although the present pilot study demonstrated the feasibility of using 1H-MRS to assess IHL in healthy normal and overweight youth, it is important to note, based on our pilot experience, that these measurements should be performed by a well-trained, dedicated clinical staff who are comfortable working with children. We originally anticipated losing some subject data due to movement artifacts (i.e., from wiggly participants). However, we were pleased that only one of 11 liver acquisitions was unusable because of motion artifact. Thus, 7–9-year-old children can successfully be kept “relatively” still and entertained during IHL acquisitions by stressing the importance of being still, practicing shallow breathing, and providing music/stories via headphones.
The most exciting findings from our pilot study were that IHL accumulation is initiated (at least in some children) before puberty and that this accumulation tends to be most noteworthy in those with presumed central adiposity and higher total adiposity. Although excessive liver fat accumulation, or hepatic steatosis, has been identified in ill or obese prepubertal21,22
children, our studies are the first to identify this phenomenon noninvasively in healthy young prepubertal children. It is particularly interesting to note that IHL stores in the current study in children were mostly in the range we have previously seen in overweight, insulin-sensitive adults (range, 0.07–3.2% vs. 0.3–7.2%) using nearly identical methodology.7
Although the highest IHL accumulation was found in the child with newly diagnosed T2DM, it is clear that significant IHL stores were also present in other apparently healthy prepubertal children (). Certainly, these noninvasive measures should prove useful in identifying early markers of the metabolic syndrome in at-risk youth and also help to elucidate whether liver lipid accumulation is a cause or consequence of tissue insulin resistance. Ongoing research from this pilot is currently measuring both IHL and intramyocellular lipids by 1
H-MRS along with insulin sensitivity by the frequently sampled intravenous glucose tolerance test in a larger cohort of 400 healthy normal and overweight prepubertal African American and white children born with normal, high, and low birth weight.
In conclusion, while our study provides important preliminary results, they are limited by our small mixed sample of male and female white and African American children and our use of HOMA to assess insulin resistance. Regardless, these preliminary data suggest that 1H-MRS may be successfully used to determine IHL in exclusively prepubertal, healthy, normal and overweight youth when assessed by a well-trained, dedicated staff who are comfortable working with children. Most importantly, IHL data may be successfully obtained in a standard pediatric clinical environment. This noninvasive measure may prove useful in identifying early markers of the metabolic syndrome in at-risk youth.