Pediatrics

Type 2 diabetes (T2D) is the result of interaction between environmental factors and a strong hereditary component. We review the heritability of T2D as well as the history of genetic and genomic research in this area. Very few T2D risk genes were identified using candidate gene and linkage-based studies, but the advent of genome-wide association studies has led to the identification of multiple genes, including several that were not previously known to play any role in T2D. Highly replicated genes, for example TCF7L2, KCNQ1 and KCNJ11, are discussed in greater detail. Taken together, the genetic loci discovered to date explain only a small proportion of the observed heritability. We discuss possible explanations for this "missing heritability", including the role of rare variants, gene-environment interactions and epigenetics. The clinical utility of current findings and avenues of future research are also discussed.

Background/Aims: Childhood cerebral palsy (CP) is associated with osteopenia and the GH-IGF axis plays an important role in bone metabolism. We studied the relationship between spinal bone mineral density (BMD) and serum IGF-1 and IGFBP-3 in children with CP. Methods: Cross-sectional study of 30 children (9 F and 21 M, ages 4.5–15) with CP. Subjects underwent dual-energy x-ray absorptiometry scans (spinal BMD), blood tests (IGF-1, IGFBP-3, Ca, P, PTH, vitamin D, osteocalcin) and urine tests (N-telopeptide). Results: Spinal BMD was decreased in children with CP (average Z-score –2.14 ± 1.08) compared to age- and gender-matched norms. IGF-1 and IGFBP-3 were also decreased compared to age-matched norms (average IGF-1 Z-score –0.74 ± 1.2, average IGFBP-3 Z-score –0.68 ± 1.2). All other blood and urine tests, including measures of calcium and vitamin D status, were normal. In 25 CP children with osteopenia (Z-score >–1), there was a trend towards correlation between spinal BMD Z-score...