Assessing truncal obesity in predicting cardiometabolic risk in children: clinical measures versus dual-energy X-ray absorptiometry.

AIM: The objectives of this study were to 1) compare the accuracy of waist:hip ratio (WHR) and waist:height ratio (WHtR) by determining their association with reference-standard measures derived from dual-energy X-ray absorptiometry (DXA) and 2) assess the relationship of DXA, WHR and WHtR to measures of dyslipidemia, insulin resistance and inflammation in children. METHODS: Subjects aged four to 21 were prospectively recruited. Truncal obesity by DXA was defined as the trunk fat:height ratio and trunk fat:nontrunk fat ratio. Three hundred and eight subjects were studied, and 246 (80%) were obese. RESULTS: There was a strong correlation between WHtR and trunk fat:height (r = 0.84, p < 0.01). DXA measures of truncal obesity had stronger correlations with measures of cardiometabolic risk than WHR and WHtR. Upon multivariable regression, only WHtR had independent associations with cholesterol/HDL, HOMA-IR and high-sensitivity c-reactive protein. CONCLUSION: WHtR is an accurate measure of truncal obesity. WHtR showed stronger associations with measures of insulin resistance and truncal obesity than WHR.

Targeted DNA Methylation Screen in the Mouse Mammary Genome Reveals a Parity-Induced Hypermethylation of Igf1r That Persists Long after Parturition.

The most effective natural prevention against breast cancer is an early first full-term pregnancy. Understanding how the protective effect is elicited will inform the development of new prevention strategies. To better understand the role of epigenetics in long-term protection, we investigated parity-induced DNA methylation in the mammary gland. FVB mice were bred or remained nulliparous and mammary glands harvested immediately after involution (early) or 6.5 months following involution (late), allowing identification of both transient and persistent changes. Targeted DNA methylation (109 Mb of Ensemble regulatory features) analysis was performed using the SureSelectXT Mouse Methyl-seq assay and massively parallel sequencing. Two hundred sixty-nine genes were hypermethylated and 128 hypomethylated persistently at both the early and late time points. Pathway analysis of the persistently differentially methylated genes revealed Igf1r to be central to one of the top identified signaling networks, and Igf1r itself was one of the most significantly hypermethylated genes. Hypermethylation of Igf1r in the parous mammary gland was associated with a reduction of Igf1r mRNA expression. These data suggest that the IGF pathway is regulated at multiple levels during pregnancy and that its modification might be critical in the protective role of pregnancy. This supports the approach of lowering IGF action for prevention of breast cancer, a concept that is currently being tested clinically.