The intra- and inter-instrument reliability of DXA based on ex vivo soft tissue measurements.

OBJECTIVE: Comparison of ex-vivo soft tissue measurements using the GE/Lunar pencil (DPX-L; GE/Lunar Co., Madison, WI) and fan beam (Prodigy dual-energy X-ray absorptiometers (DXA) GE/Lunar Co.). RESEARCH METHODS AND PROCEDURES: Intra-instrument reliability was assessed by repeatedly scanning soft tissue phantoms for lean tissue (water) and fat tissue (methanol) using one DPX-L and two identical Prodigy DXAs at fast, medium, and slow scan modes. For each machine, 10 scans of each phantom were performed at each scan speed. The number of scans per instrument totaled 60. Data were analyzed using ANOVA to ascertain whether scan speed affected the intra-instrument reliability and to test whether soft tissue measurements differed among instruments. Percentage fat (phantom density) was the outcome variable. RESULTS: Intra-instrument reliability, expressed as coefficient of variation, ranged between 0.7% and 5.2% for the DPX-L and 0.4% and 4.5% for the Prodigy, with the lowest coefficients of variation observed when scanning the fat tissue phantom. Scan speed also affected the intra-instrument reliability (p < 0.01). Furthermore, differences in the measurement of percentage body fat for both the lean and fat tissue phantoms were observed among all three absorptiometers (all p < 0.01). After adjusting for scan speed, differences persisted for all three instruments. DISCUSSION: Intra- and inter-instrument reliability of DXA machines, even those from the same manufacturer, remains unpredictable. Thus, when measuring body composition using DXA, it is important to consider that even in the absence of measurement bias, the use of different DXA machines, particularly when using a variety of speed settings, will increase the residual error around the true value.

A C-reactive protein promoter polymorphism is associated with type 2 diabetes mellitus in Pima Indians.

Linkage analysis has identified a susceptibility locus for type 2 diabetes mellitus (T2DM) on chromosome 1q21-q23 in several populations. Results from recent prospective studies indicate that increased levels of C-reactive protein (CRP), a marker of immune system activation, are predictive of diabetes, independent of adiposity. Because CRP is located on 1q21, we considered it a potential positional candidate gene for T2DM. We therefore evaluated CRP and the nearby serum amyloid P-component, APCS, which is structurally similar to CRP, as candidate diabetes susceptibility genes. Approximately 10.9kb of the CRP-APCS locus was screened for polymorphisms using denaturing high performance liquid chromatography and direct sequencing. We identified 27 informative polymorphisms, including 26 single nucleotide polymorphisms (SNPs) and 1 insertion/deletion, which were divided into 7 linkage disequilibrium clusters. We genotyped representative SNPs in approximately 1300 Pima samples and found a single variant in the CRP promoter (SNP 133552) that was associated with T2DM (P=0.014), as well as a common haplotype (CGCG) that was associated with both T2DM (P=0.029) and corrected insulin response, a surrogate measure of insulin secretion in non-diabetic subjects (P=0.050). Linkage analyses that adjusted for the effect of these polymorphisms indicated that they do not in themselves account for the observed linkage with T2DM on chromosome 1q. However, these findings suggest that variation within the CRP locus may play a role in diabetes susceptibility in Pima Indians.