A cross-sectional study of osteocalcin and body fat measures among obese adolescents.

UNLABELLED: Osteocalcin (OCN), a marker of osteoblast activity, has been implicated in the regulation of energy metabolism by the skeleton and thus may affect body fat measures. OBJECTIVE: To examine the relationships of OCN to body fat measures and whether they vary according to markers of energy and vitamin D metabolism. DESIGN AND METHODS: Data were obtained from 58 obese adolescents aged 13-17.9 years (38 females, 8 black or African-American). Total fat mass (FM) [dual X-ray absorptiometry (DXA)] and visceral adipose tissue (VAT) [computerized axial tomography (CT)] were calculated. Blood tests included leptin, OCN, 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), thyroid function tests, and triglycerides. Markers of glucose metabolism were obtained from fasting and OGTT samples. RESULTS AND CONCLUSIONS: Adolescents with 25(OH)D <20 ng mL(-1) were considered deficient (n = 17/58); none had high PTH (PTH ≥ 65 pg mL(-1) ). OCN was associated with lower VAT (-84.27 ± 33.89 mm(2) ) and BMI (-0.10 ± 0.05 kg m(-2) ), not FM (P = 0.597) in a core model including age, sex, race, geographic latitude, summer, height z-score, and tanner stage. Adding 25(OH)D deficiency and PTH attenuated the inverse association of OCN to VAT. There was a significant interaction of OCN and 25(OH)D deficiency on FM (0.37 ± 0.18 kg, P = 0.041) and BMI (0.28 ± 0.10 kg m(-2) , P = 0.007) in this adjusted model, which was further explained by leptin. Adding A1C to the core model modified the relationship of OCN to VAT (-93.08 ± 35.05 mm(2) , P = 0.011), which was further explained by HOMA-IR. In summary, these findings provide initial evidence for a relationship between OCN and body fat measures that is dependent on energy metabolism and vitamin D status among obese adolescents.

The toxic effects of cigarette additives. Philip Morris' project mix reconsidered: an analysis of documents released through litigation.

BACKGROUND: In 2009, the promulgation of US Food and Drug Administration (FDA) tobacco regulation focused attention on cigarette flavor additives. The tobacco industry had prepared for this eventuality by initiating a research program focusing on additive toxicity. The objective of this study was to analyze Philip Morris' Project MIX as a case study of tobacco industry scientific research being positioned strategically to prevent anticipated tobacco control regulations. METHODS AND FINDINGS: We analyzed previously secret tobacco industry documents to identify internal strategies for research on cigarette additives and reanalyzed tobacco industry peer-reviewed published results of this research. We focused on the key group of studies conducted by Phillip Morris in a coordinated effort known as "Project MIX." Documents showed that Project MIX subsumed the study of various combinations of 333 cigarette additives. In addition to multiple internal reports, this work also led to four peer-reviewed publications (published in 2001). These papers concluded that there was no evidence of substantial toxicity attributable to the cigarette additives studied. Internal documents revealed post hoc changes in analytical protocols after initial statistical findings indicated an additive-associated increase in cigarette toxicity as well as increased total particulate matter (TPM) concentrations in additive-modified cigarette smoke. By expressing the data adjusted by TPM concentration, the published papers obscured this underlying toxicity and particulate increase. The animal toxicology results were based on a small number of rats in each experiment, raising the possibility that the failure to detect statistically significant changes in the end points was due to underpowering the experiments rather than lack of a real effect. CONCLUSION: The case study of Project MIX shows tobacco industry scientific research on the use of cigarette additives cannot be taken at face value. The results demonstrate that toxins in cigarette smoke increase substantially when additives are put in cigarettes, including the level of TPM. In particular, regulatory authorities, including the FDA and similar agencies elsewhere, could use the Project MIX data to eliminate the use of these 333 additives (including menthol) from cigarettes.

Relation of body fat indexes to vitamin D status and deficiency among obese adolescents.

BACKGROUND: Data on the relation between vitamin D status and body fat indexes in adolescence are lacking. OBJECTIVE: The objective was to identify factors associated with vitamin D status and deficiency in obese adolescents to further evaluate the relation of body fat indexes to vitamin D status and deficiency. DESIGN: Data from 58 obese adolescents were obtained. Visceral adipose tissue (VAT) was measured by computed tomography. Dual-energy X-ray absorptiometry was used to measure total bone mineral content, bone mineral density, body fat mass (FM), and lean mass. Relative measures of body fat were calculated. Blood tests included measurements of 25-hydroxyvitamin D [25(OH)D], parathyroid hormone (PTH), osteocalcin, type I collagen C-telopeptide, hormones, and metabolic factors. Vitamin D deficiency was defined as 25(OH)D < 20 ng/mL. PTH elevation was defined as PTH > 65 ng/mL. RESULTS: The mean (+/-SD) age of the adolescents was 14.9 +/- 1.4 y; 38 (66%) were female, and 8 (14%) were black. The mean (+/-SD) body mass index (in kg/m(2)) was 36 +/- 5, FM was 40.0 +/- 5.5%, and VAT was 12.4 +/- 4.3%. Seventeen of the adolescents were vitamin D deficient, but none had elevated PTH concentrations. Bone mineral content and bone mineral density were within 2 SDs of national standards. In a multivariate analysis, 25(OH)D decreased by 0.46 +/- 0.22 ng/mL per 1% increment in FM (beta +/- SE, P = 0.05), whereas PTH decreased by 0.78 +/- 0.29 pg/mL per 1% increment in VAT (P = 0.01). CONCLUSIONS: To the best of our knowledge, our results show for the first time that obese adolescents with 25(OH)D deficiency, but without elevated PTH concentrations, have a bone mass within the range of national standards (+/-2 SD). The findings provide initial evidence that the distribution of fat may be associated with vitamin D status, but this relation may be dependent on metabolic factors. This study was registered at www.clinicaltrials.gov as NCT00209482, NCT00120146.