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@ARTICLE{Zhu:181493,
      author       = {A. Zhu$^*$ and S. Kuznia$^*$ and T. Niedermaier$^*$ and B.
                      Holleczek and B. Schöttker$^*$ and H. Brenner$^*$},
      title        = {{C}onsistent {I}nverse {A}ssociations of {T}otal,
                      '{B}ioavailable', {F}ree, and '{N}on-{B}ioavailable'
                      {V}itamin {D} with {I}ncidence of {D}iabetes among {O}lder
                      {A}dults with {L}ower {B}aseline {H}b{A}1c $(≤6\%)$
                      {L}evels.},
      journal      = {Nutrients},
      volume       = {14},
      number       = {16},
      issn         = {2072-6643},
      address      = {Basel},
      publisher    = {MDPI},
      reportid     = {DKFZ-2022-02028},
      pages        = {3282},
      year         = {2022},
      note         = {#EA:C070#LA:C070#},
      abstract     = {Serum 25-hydroxyvitamin (25(OH)D) levels are inversely
                      associated with risk of diabetes. The 'free hormone
                      hypothesis' suggests potential effects to be mainly related
                      to concentrations of 'bioavailable' and free rather than
                      total 25(OH)D. We assessed associations of serum
                      concentrations of vitamin D-binding protein (VDBP), as well
                      as total 'bioavailable', complementary 'non-bioavailable',
                      and free 25(OH)D, with the risk of developing diabetes among
                      non-diabetic older adults in a large population-based cohort
                      study in Germany.We included 4841 non-diabetic older adults
                      aged 50-75 years at the baseline exam from the ESTHER cohort
                      conducted in Saarland, Germany, in 2001-2002. Concentrations
                      of 'bioavailable' and free 25(OH)D were derived from serum
                      concentrations of VDBP, total 25(OH)D, and albumin.
                      Incidence of diabetes was ascertained during up to 14 years
                      of follow-up. Associations were quantified by multivariable
                      Cox proportional hazards regression models with
                      comprehensive confounder adjustment.During a median
                      follow-up of 10.6 years, 837 non-diabetic participants
                      developed diabetes. We observed similar inverse associations
                      with developing diabetes for VDBP (hazard ratio (HR) for
                      lowest versus highest quintile: 1.37, $95\%$ confidence
                      interval (CI): 1.09, 1.72), total 25(OH)D (HR: 1.31, $95\%$
                      CI: 1.03, 1.66), and 'non-bioavailable' 25(OH)D (HR: 1.30,
                      $95\%$ CI: 1.02, 1.65). Associations were smaller and
                      statistically insignificant for 'bioavailable' and free
                      25(OH)D. However, associations of total 'non-bioavailable',
                      'bioavailable', and free 25(OH)D with incidence of diabetes
                      were much stronger among, and essentially restricted to,
                      participants with lower baseline HbA1c $(≤6\%)$
                      levels.This large prospective cohort study of older
                      Caucasian adults, in agreement with results from randomized
                      trials and Mendelian randomization studies, supports a
                      protective effect of vitamin D against development of
                      diabetes. The 'free hormone theory' may not be relevant in
                      this context. However, our results underline the importance
                      of adequate vitamin D status among those who have not yet
                      shown any sign of impaired glucose tolerance.},
      keywords     = {bioavailable 25(OH)D (Other) / free 25(OH)D (Other) / type
                      2 diabetes (Other) / vitamin D (Other) / vitamin D-binding
                      protein (Other)},
      cin          = {C070 / C120 / HD01},
      ddc          = {610},
      cid          = {I:(DE-He78)C070-20160331 / I:(DE-He78)C120-20160331 /
                      I:(DE-He78)HD01-20160331},
      pnm          = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
      pid          = {G:(DE-HGF)POF4-313},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:36014788},
      doi          = {10.3390/nu14163282},
      url          = {https://inrepo02.dkfz.de/record/181493},
}