TY  - JOUR
A1  - Dörhöfer, Lena
A1  - Lammert, Alexander
A1  - Krane, Vera
A1  - Gorski, Mathias
A1  - Banas, Bernhard
A1  - Wanner, Christoph
A1  - Krämer, Bernhard K.
A1  - Heid, Iris M.
A1  - Böger, Carsten A.
T1  - Study design of DIACORE (DIAbetes COhoRtE) - a cohort study of patients with diabetes mellitus type 2
JF  - BMC Medical Genetics
N2  - Background: Diabetes mellitus type 2 (DM2) is highly associated with increased risk for chronic kidney disease (CKD), end stage renal disease (ESRD) and cardiovascular morbidity. Epidemiological and genetic studies generate hypotheses for innovative strategies in DM2 management by unravelling novel mechanisms of diabetes complications, which is essential for future intervention trials. We have thus initiated the DIAbetes COhoRtE study (DIACORE). 
Methods: DIACORE is a prospective cohort study aiming to recruit 6000 patients of self-reported Caucasian ethnicity with prevalent DM2 for at least 10 years of follow-up. Study visits are performed in University-based recruiting clinics in Germany using standard operating procedures. All prevalent DM2 patients in outpatient clinics surrounding the recruiting centers are invited to participate. At baseline and at each 2-year follow-up examination, patients are subjected to a core phenotyping protocol. This includes a standardized online questionnaire and physical examination to determine incident micro-and macrovascular DM2 complications, malignancy and hospitalization, with a primary focus on renal events. Confirmatory outcome information is requested from patient records. Blood samples are obtained for a centrally analyzed standard laboratory panel and for biobanking of aliquots of serum, plasma, urine, mRNA and DNA for future scientific use. A subset of the cohort is subjected to extended phenotyping, e. g. sleep apnea screening, skin autofluorescence measurement, non-mydriatic retinal photography and non-invasive determination of arterial stiffness. 
Discussion: DIACORE will enable the prospective evaluation of factors involved in DM2 complication pathogenesis using high-throughput technologies in biosamples and genetic epidemiological studies.
KW  - chronic kidney-disease
KW  - stage renal-disease
KW  - glomerular-filtration-rate
KW  - genome-wide association
KW  - blood-glucose control
KW  - genetics
KW  - serum creatinine
KW  - cardiovascular disease
KW  - replacement therapy
KW  - United States
KW  - risk factors
KW  - diabetes mellitus type 2
KW  - diabetic nephropathy
KW  - end stage renal disease
KW  - cardiovascular morbidity
KW  - diabetes complications
KW  - epidemiology
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122040
SN  - 1471-2350
VL  - 14
IS  - 25
ER  - 
TY  - JOUR
A1  - Brandenburg, Vincent M.
A1  - Kramann, Rafael
A1  - Koos, Ralf
A1  - Krueger, Thilo
A1  - Schurgers, Leon
A1  - Mühlenbruch, Georg
A1  - Hübner, Sinah
A1  - Gladziwa, Ulrich
A1  - Drechler, Christiane
A1  - Ketteler, Markus
T1  - Relationship between sclerostin and cardiovascular calcification in hemodialysis patients: a cross-sectional study
JF  - BMC Nephrology
N2  - Background: Sclerostin is a Wnt pathway antagonist regulating osteoblast activity and bone turnover. Here, we assessed the potential association of sclerostin with the development of coronary artery (CAC) and aortic valve calcifications (AVC) in haemodialysis (HD) patients. Methods: We conducted a cross-sectional multi-slice computed tomography (MS-CT) scanning study in 67 chronic HD patients (59.4 +/- 14.8 yrs) for measurement of CAC and AVC. We tested established biomarkers as well as serum sclerostin (ELISA) regarding their association to the presence of calcification. Fifty-four adults without relevant renal disease served as controls for serum sclerostin levels. Additionally, sclerostin expression in explanted aortic valves from 15 dialysis patients was analysed ex vivo by immunohistochemistry and mRNA quantification (Qt-RT-PCR). Results: CAC (Agatston score > 100) and any AVC were present in 65% and in 40% of the MS-CT patient group, respectively. Serum sclerostin levels (1.53 +/- 0.81 vs 0.76 +/- 0.31 ng/mL, p < 0.001) were significantly elevated in HD compared to controls and more so in HD patients with AVC versus those without AVC (1.78 +/- 0.84 vs 1.35 +/- 0.73 ng/mL, p = 0.02). Multivariable regression analysis for AVC revealed significant associations with higher serum sclerostin. Ex vivo analysis of uraemic calcified aortic valves (n = 10) revealed a strong sclerostin expression very close to calcified regions (no sclerostin staining in non-calcified valves). Correspondingly, we observed a highly significant upregulation of sclerostin mRNA in calcified valves compared to non-calcified control valves. Conclusion: We found a strong association of sclerostin with calcifying aortic heart valve disease in haemodialysis patients. Sclerostin is locally produced in aortic valve tissue adjacent to areas of calcification.
KW  - coronary calcification
KW  - cardiovascular disease
KW  - aortic valve disease
KW  - calcium
KW  - mortality
KW  - sclerostin
KW  - aortic valve
KW  - bone formation
KW  - computed tomography
KW  - fetuin A
KW  - risk factors
KW  - GLA protein UCMGP
KW  - kidney-disease CKD
KW  - coronary-artery calcification
KW  - hemodialysis
KW  - mineral metabolism
KW  - vascular calcification
KW  - renal osteodystrophy
Y1  - 2013
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-122070
SN  - 1471-2369
VL  - 14
IS  - 219
ER  -