title: Parathyroid hormone is a plausible mediator for the metabolic syndrome in the morbidly obese: a cross-sectional study.
abstract: BACKGROUND
  The biological mechanisms in the association between the metabolic syndrome (MS) and various biomarkers, such as 25-hydroxyvitamin D (vit D) and magnesium, are not fully understood. Several of the proposed predictors of MS are also possible predictors of parathyroid hormone (PTH). We aimed to explore whether PTH is a possible mediator between MS and various possible explanatory variables in morbidly obese patients.
  
  
  METHODS
  Fasting serum levels of PTH, vit D and magnesium were assessed in a cross-sectional study of 1,017 consecutive morbidly obese patients (68% women). Dependencies between MS and a total of seven possible explanatory variables as suggested in the literature, including PTH, vit D and magnesium, were specified in a path diagram, including both direct and indirect effects. Possible gender differences were also included. Effects were estimated using Bayesian path analysis, a multivariable regression technique, and expressed using standardized regression coefficients.
  
  
  RESULTS
  Sixty-eight percent of the patients had MS. In addition to type 2 diabetes and age, both PTH and serum phosphate had significant direct effects on MS; 0.36 (95% Credibility Interval (CrI) [0.15, 0.57]) and 0.28 (95% CrI [0.10,0.47]), respectively. However, due to significant gender differences, an increase in either PTH or phosphate corresponded to an increased OR for MS in women only. All proposed predictors of MS had significant direct effects on PTH, with vit D and phosphate the strongest; -0.27 (95% CrI [-0.33,-0.21]) and -0.26 (95% CrI [-0.32,-0.20]), respectively. Though neither vit D nor magnesium had significant direct effects on MS, for women they both affected MS indirectly, due to the strong direct effect of PTH on MS. For phosphate, the indirect effect on MS, mediated through serum calcium and PTH, had opposite sign than the direct effect, resulting in the total effect on MS being somewhat attenuated compared to the direct effect only.
  
  
  CONCLUSIONS
  Our results indicate that for women PTH is a plausible mediator in the association between MS and a range of explanatory variables, including vit D, magnesium and phosphate.
authors.affiliation: Department of Biostatistics, Institute of Basic Medical Sciences, University of Oslo, Norway. jo.roislien@medisin.uio.no
authors.forename: Jo
authors.initials: J
authors.lastname: Røislien
authors.forename: Ben
authors.initials: B
authors.lastname: Van Calster
authors.forename: Jøran
authors.initials: J
authors.lastname: Hjelmesæth
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D016014:Linear Models; D016015:Logistic Models; D008274:Magnesium / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood* / Q000453:epidemiology; D008875:Middle Aged; D009664:Norway / Q000453:epidemiology; D009767:Obesity, Morbid / Q000097:blood* / Q000453:epidemiology; D016017:Odds Ratio; D010281:Parathyroid Hormone / Q000097:blood*; D010710:Phosphates / Q000097:blood; D018570:Risk Assessment; D012307:Risk Factors; D012737:Sex Factors; D014807:Vitamin D / Q000097:blood
chemical_list: D015415:Biomarkers; C470125:PTH protein, human; D010281:Parathyroid Hormone; D010710:Phosphates; D014807:Vitamin D; D008274:Magnesium