TY  - JOUR
A1  - Hocher, Berthold
A1  - Groen, Hans Jürgen
A1  - Schumann, Claudia
A1  - Tsuprykov, Oleg
A1  - Seifert, Susanne
A1  - Hitzler, Walter E.
A1  - Armbruster, Franz Paul
T1  - Vitamin D status from dried capillary blood samples
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Background: Given the huge impact of vitamin D deficiency on a broad spectrum of diseases such as rickets, osteoporosis, mineral bone disease-vascular calcification syndrome, infectious diseases, but also several types of cancer and CNS diseases, reliable and simple methods to analyze the vitamin D status are urgently needed.
 Methods: We developed an easy technique to determine the 25-OH vitamin D status from dried blood samples on filter paper. This allows determination of the 25-OH vitamin D status independently of venous blood taking, since only sampling of capillary blood is required for this new method. We compared the results of vitamin D measurements from venous blood of 96 healthy blood donors with those from capillary blood taken from the same patients at the same time. The capillary blood was dried on filter paper using the D-Vital ID dry-blood collection system.
 Results: 25-OH vitamin D concentration data from extracted dried capillary blood filters correlated very well with data obtained after direct measurement of venous blood samples of the same blood donor (R: 0.7936; p<0.0001). The correlation was linear over the whole range of 25-OH vitamin D concentrations seen in this study. A Bland-Altman plot revealed good agreement between both tests.
 Conclusions: The D-Vital ID dry-blood collection system showed an excellent performance as compared to the classical way of 25-OH vitamin D measurement from venous blood. This new technique will facilitate easy and reliable measurement for vitamin D status, in particular, in rural or isolated areas, developing countries, and field studies.
KW  - 25-OH vitamin D
KW  - filter paper
KW  - capillary blood
KW  - new analysis method
Y1  - 2012
U6  - https://doi.org/10.7754/Clin.Lab.2012.120429
SN  - 1433-6510
VL  - 58
IS  - 7-8
SP  - 851
EP  - 855
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Henze, Andrea
A1  - Espe, Katharina M.
A1  - Wanner, Christoph
A1  - Krane, Vera
A1  - Raila, Jens
A1  - Hocher, Berthold
A1  - Schweigert, Florian J.
A1  - Drechsler, Christiane
T1  - Transthyretin predicts cardiovascular outcome in hemodialysis patients with type 2 diabetes
JF  - Diabetes care
N2  - OBJECTIVE-BMI and albumin are commonly accepted parameters to recognize wasting in dialysis patients and are powerful predictors of morbidity and mortality. However, both parameters reveal limitations and may not cover the entire range of patients with wasting. The visceral protein transthyretin (TTR) may be helpful in overcoming the diagnostic and prognostic gap. Therefore, the aim of this study was to assess the association of TTR with morbidity and mortality in hemodialysis patients.
 RESEARCH DESIGN AND METHODS-The TTR concentration was determined in plasma samples of 1,177 hemodialysis patients with type 2 diabetes. Cox regression analyses were used to determine hazard ratios (HRs) for the risk of cardiovascular end points (CVEs) and mortality according to quartiles of TTR concentration for the total study cohort and the subgroups BMI >= 23 kg/m(2), albumin concentration >= 3.8 g/dL, and a combination of both.
 RESULTS-A low TTR concentration was associated with an increased risk for CVE for the total study cohort (HR 1.65 [95% CI 1.27-2.14]), patients with BMI >= 23 kg/m(2) (1.70 [1.22-2.37]), albumin >= 3.8 g/dL (1.68 [1.17-2.42]), and the combination of both (1.69 [1.13-2.53]). Additionally, a low TTR concentration predicted mortality for the total study cohort (1.79 [1.43-2.24]) and patients with BMI >= 23 kg/m(2) (1.46 [1.09-1.95]).
 CONCLUSIONS-The current study demonstrated that TTR is a useful predictor for cardiovascular outcome and mortality in diabetic hemodialysis patients. TTR was particularly useful in patients who were not identified to be at risk by BMI or albumin status.
Y1  - 2012
U6  - https://doi.org/10.2337/dc12-0455
SN  - 0149-5992
VL  - 35
IS  - 11
SP  - 2365
EP  - 2372
PB  - American Diabetes Association
CY  - Alexandria
ER  - 
TY  - JOUR
A1  - Chen, You-Peng
A1  - Li, Jian
A1  - Wang, Zi-Neng
A1  - Reichetzeder, Christoph
A1  - Xu, Hao
A1  - Gong, Jian
A1  - Chen, Guang-Ji
A1  - Pfab, Thiemo
A1  - Xiao, Xiao-Min
A1  - Hocher, Berthold
T1  - Renin angiotensin aldosterone system and glycemia in pregnancy
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Background: The renin-angiotensin-aldosterone system (RAAS) is involved in the pathogenesis of insulin resistance and type 2 diabetes in the general population. The RAAS is activated during pregnancy. However, it is unknown whether the RAAS contributes to glycemia in pregnant women.
 Methods: Plasma renin activity (PRA) and plasma aldosterone levels were quantified at delivery in 689 Chinese mothers. An oral glucose tolerance test in fasted women was performed in the second trimester of pregnancy. The diagnosis of gestational diabetes mellitus (GDM) and impaired glucose tolerance during pregnancy were made according to the guidelines of the Chinese Society of Obstetrics.
 Results: Plasma aldosterone was significantly higher in pregnant women with GDM as compared to those without impairment of glycemic control (normal pregnancies: 0.27 +/- 0.21 ng/mL, GDM: 0.36 +/- 0.30 ng/mL; p<0.05). Regression analyses revealed that PRA was negatively correlated with fasting blood glucose (FBG) (R-2 = 0.03, p = 0.007), whereas plasma aldosterone and aldosterone/PRA ratio were positively correlated with FBG (R-2 = 0.05, p<0.001 and R-2 = 0.03, p = 0.007, respectively). Multivariable regression analysis models considering relevant confounding factors confirmed these findings.
 Conclusions: This study demonstrated that fasting blood glucose in pregnant women is inversely correlated with the PRA, whereas plasma aldosterone showed a highly significant positive correlation with fasting blood glucose during pregnancy. Moreover, plasma aldosterone is significantly higher in pregnant women with GDM as compared to those women with normal glucose tolerance during pregnancy. Although causality cannot be proven in association studies, these data may indicate that the RAAS during pregnancy contributes to the pathogenesis of insulin resistance/new onset of diabetes during pregnancy.
KW  - Renin-angiotensin-aldosterone system
KW  - pregnancy
KW  - fasting blood glucose
KW  - glycemic control
Y1  - 2012
SN  - 1433-6510
VL  - 58
IS  - 5-6
SP  - 527
EP  - 533
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Schmerbach, K.
A1  - Kalk, Philipp.
A1  - Wengenmayer, Christina
A1  - Lucht, K.
A1  - Unger, T.
A1  - Hocher, Berthold
A1  - Thoene-Reineke, C.
T1  - Renal outcome in equipotent Antihypertensive Treatment with Telmisartan, Ramipril and in combination in SHR-SP Rats
JF  - Clinical laboratory : the peer reviewed journal for clinical laboratories and laboratories related to blood transfusion
N2  - Background: The ONTARGET trial revealed an association of ACEI/ARB combination treatment (telmisartan and ramipril) with adverse renal outcome versus respective monotherapy; preclinical evidence regarding renal outcome in ACEI/ARB combination treatment is scarce.
 Methods: Spontaneously hypertensive stroke prone rats (SHR-SP) rats on a salt-rich diet were randomly allocated to 4 groups: SHR (untreated, n = 24), SHR + telmisartan (SHR-T, 2.39 +/- 0.69 mg/kg bw; n = 27), SHR + ramipril (SHR-R, 6.28 +/- 3.48 mg/kg bw; n = 27) and combination treatment (SHR-TR, 0.51 +/- 0.14 mg/kg bw; same dose for telmisartan and ramipril; n = 26). Study duration was 12 weeks, blood pressure was assessed weekly and doses were adjusted to maintain equal blood pressure. Finally, blood and urine samples were obtained and kidneys were harvested for histological studies.
 Results: Blood pressure in untreated rats rose to a maximum of 239 mmHg, whereas in all treatment groups it remained stable betvveen 140 and 150 mmHg. Mortality was 50% in the untreated group, whereas all treatment groups survived completely. Renal function - as indicated by plasma urea and cystatin c - was significantly worse in SHR-TR animals compared to all other groups. With plasma creatinine a similar trend was observed. All treatment options significantly decreased albuminuria. Renal glomerulosclerosis was decreased by monotherapy, whereas combination therapy failed to have a significant effect. Interstitial fibrosis was decreased to a similar extent by all treatment options.
 Conclusions: ACEI/ARB combination treatment failed to render significant additional benefits on renal outcome in hypertensive rats when compared to monotherapy. Instead our data indicate that dual RAAS blockade might have an adverse effect on kidney function and histology when compared to monotherapy in salt-loaded SHR-SP.
KW  - Renal failure
KW  - angiotensin receptor blockers
KW  - ACE inhibitors
KW  - telmisartan
KW  - ramipril
Y1  - 2012
U6  - https://doi.org/10.7754/Clin.Lab.2011.110622
SN  - 1433-6510
VL  - 58
IS  - 7-8
SP  - 625
EP  - 633
PB  - Clin Lab Publ., Verl. Klinisches Labor
CY  - Heidelberg
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Reichetzeder, Christoph
A1  - Alter, Markus L.
T1  - Renal and cardiac effects of DPP-4 inhibitors - from preclinical development to clinical research
JF  - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie
N2  - Inhibitors of type 4 dipeptidyl peptidase (DDP-4) were developed and approved for the oral treatment of type 2 diabetes. Its mode of action is to inhibit the degradation of incretins, such as type 1 glucagon like peptide (GLP-1), and GIP. GLP-1 stimulates glucose-dependent insulin secretion from pancreatic beta-cells and suppresses glucagon release from alpha-cells, thereby improving glucose control. Besides its action on the pancreas type 1 glucagon like peptide has direct effects on the heart, vessels and kidney mainly via the type 1 glucagon like peptide receptor (GLP-1R). Moreover, there are substrates of DPP-4 beyond incretins that have proven renal and cardiovascular effects such as BNP/ANP, NPY, PYY or SDF-1 alpha. Preclinical evidence suggests that DPP-4 inhibitors may be effective in acute and chronic renal failure as well as in cardiac diseases like myocardial infarction and heart failure. Interestingly, large cardiovascular meta-analyses of combined Phase II/III clinical trials with DPP-4 inhibitors point all in the same direction: a potential reduction of cardiovascular events in patients treated with these agents. A pooled analysis of pivotal Phase III, placebo-controlled, registration studies of linagliptin further showed a significant reduction of urinary albumin excretion after 24 weeks of treatment. The observation suggests direct renoprotective effects of DPP-4 inhibition that may go beyond its glucose-lowering potential. Type 4 dipeptidyl peptidase inhibitors have been shown to be very well tolerated in general, but for those excreted via the kidney dose adjustments according to renal function are needed to avoid side effects. In conclusion, the direct cardiac and renal effects seen in preclinical studies as well as meta-analysis of clinical trials may offer additional potentials - beyond improvement of glycemic control - for this newer class of drugs, such as acute kidney failure, chronic kidney failure as well as acute myocardial infarction and heart failure.
KW  - DDP-4 inhibition
KW  - Diabetes
KW  - GLP-1
KW  - Cardiovascular effects
KW  - Myocardial infarction
KW  - Kidney
KW  - Diabetic nephropathy
KW  - Acute renal failure
Y1  - 2012
U6  - https://doi.org/10.1159/000339028
SN  - 1420-4096
VL  - 36
IS  - 1
SP  - 65
EP  - 84
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Chen, You-Peng
A1  - Xiao, Xiao-Min
A1  - Li, Jian
A1  - Reichetzeder, Christoph
A1  - Wang, Zi-Neng
A1  - Hocher, Berthold
T1  - Paternal body mass index (BMI) is associated with offspring intrauterine growth in a gender dependent manner
JF  - PLoS one
N2  - Background: Environmental alternations leading to fetal programming of cardiovascular diseases in later life have been attributed to maternal factors. However, animal studies showed that paternal obesity may program cardio-metabolic diseases in the offspring. In the current study we tested the hypothesis that paternal BMI may be associated with fetal growth.
 Methods and Results: We analyzed the relationship between paternal body mass index (BMI) and birth weight, ultrasound parameters describing the newborn's body shape as well as parameters describing the newborns endocrine system such as cortisol, aldosterone, renin activity and fetal glycated serum protein in a birth cohort of 899 father/mother/child triplets. Since fetal programming is an offspring sex specific process, male and female offspring were analyzed separately. Multivariable regression analyses considering maternal BMI, paternal and maternal age, hypertension during pregnancy, maternal total glycated serum protein, parity and either gestational age (for birth weight) or time of ultrasound investigation (for ultrasound parameters) as confounding showed that paternal BMI is associated with growth of the male but not female offspring. Paternal BMI correlated with birth parameters of male offspring only: birth weight; biparietal diameter, head circumference; abdominal diameter, abdominal circumference; and pectoral diameter. Cortisol was likewise significantly correlated with paternal BMI in male newborns only.
 Conclusions: Paternal BMI affects growth of the male but not female offspring. Paternal BMI may thus represent a risk factor for cardiovascular diseases of male offspring in later life. It remains to be demonstrated whether this is linked to an offspring sex specific paternal programming of cortisol secretion.
Y1  - 2012
U6  - https://doi.org/10.1371/journal.pone.0036329
SN  - 1932-6203
VL  - 7
IS  - 5
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - JOUR
A1  - Hocher, Berthold
A1  - Armbruster, Franz Paul
A1  - Stöva, Stanka
A1  - Reichetzeder, Christoph
A1  - Groen, Hans Jürgen
A1  - Lieker, Ina
A1  - Khadzhynov, Dmytro
A1  - Slowinski, Torsten
A1  - Roth, Heinz Jürgen
T1  - Measuring Parathyroid Hormone (PTH) in patients with oxidative stress - do we need a fourth generation Parathyroid Hormone assay?
JF  - PLoS one
N2  - Oxidation of PTH at methionine residues results in loss of biological activity. PTH may be oxidized in patients with renal disease. The aim of this study was to develop an assay considering oxidation of PTH. Oxidized hPTH was analyzed by high resolution nano-liquid chromatography coupled to ESI-FTT tandem mass spectrometry (nanoLC-ESI-FT-MS/MS) directly and after proteolytic cleavage. The oxidized hPTH(1-84) sample shows TIC-peaks at 18-20 min and several mass peaks due to mass shifts caused by oxidations. No significant signal for oxidized hPTH(1-84) species after removal of oxidized PTH molecules by a specific column with monoclonal antibodies (MAB) raised against the oxidized hPTH was detectable. By using this column in samples from 18 patients on dialysis we could demonstrate that measured PTH concentrations were substantially lower when considering oxidized forms of PTH. The relationship between PTH concentrations determined directly and those concentrations measured after removal of the oxidized PTH forms varies substantially. In some patients only 7% of traditionally measured PTH was free of oxidation, whereas in other patients 34% of the traditionally measured PTH was real intact PTH. In conclusion, a huge but not constant proportion of PTH molecules are oxidized in patients requiring dialysis. Since oxidized PTH is biologically inactive, the currently used methods to detect PTH in daily clinical practice may not adequately reflect PTH-related bone and cardiovascular abnormalities in patients on dialysis.
Y1  - 2012
U6  - https://doi.org/10.1371/journal.pone.0040242
SN  - 1932-6203
VL  - 7
IS  - 7
PB  - PLoS
CY  - San Fransisco
ER  - 
TY  - CHAP
A1  - Espe, Katharina M.
A1  - Raila, Jens
A1  - Henze, Andrea
A1  - Blouin, Katja
A1  - Schneider, A.
A1  - Schmiedeke, D.
A1  - Krane, Vera
A1  - Schweigert, Florian J.
A1  - Hocher, Berthold
A1  - Wanner, Christoph
A1  - Drechsler, Christiane
T1  - Low vitamin E plasma levels are associated with cerebrovascular events and mortality in hemodialysis patients
T2  - Annals of nutrition & metabolism : journal of nutrition, metabolic diseases and dietetics ; an official journal of International Union of Nutritional Sciences (IUNS)
Y1  - 2012
SN  - 0250-6807
VL  - 60
IS  - 2
SP  - 137
EP  - 137
PB  - Karger
CY  - Basel
ER  - 
TY  - JOUR
A1  - Nair, Anil V.
A1  - Hocher, Berthold
A1  - Verkaart, Sjoerd
A1  - van Zeeland, Femke
A1  - Pfab, Thiemo
A1  - Slowinski, Torsten
A1  - Chen, You-Peng
A1  - Schlingmann, Karl Peter
A1  - Schaller, Andre
A1  - Gallati, Sabina
A1  - Bindels, Rene J.
A1  - Konrad, Martin
A1  - Hönderop, Joost G.
T1  - Loss of insulin-induced activation of TRPM6 magnesium channels results in impaired glucose tolerance during pregnancy
JF  - Proceedings of the National Academy of Sciences of the United States of America
N2  - Hypomagnesemia affects insulin resistance and is a risk factor for diabetes mellitus type 2 (DM2) and gestational diabetes mellitus (GDM). Two single nucleotide polymorphisms (SNPs) in the epithelial magnesium channel TRPM6 ((VI)-I-1393, (KE)-E-1584) were predicted to confer susceptibility for DM2. Here, we show using patch clamp analysis and total internal reflection fluorescence microscopy, that insulin stimulates TRPM6 activity via a phosphoinositide 3-kinase and Rac1-mediated elevation of cell surface expression of TRPM6. Interestingly, insulin failed to activate the genetic variants TRPM6 ((VI)-I-1393) and TRPM6((KE)-E-1584), which is likely due to the inability of the insulin signaling pathway to phosphorylate TRPM6(T-1391) and TRPM6(S-1583). Moreover, by measuring total glycosylated hemoglobin (TGH) in 997 pregnant women as a measure of glucose control, we demonstrate that TRPM6((VI)-I-1393) and TRPM6((KE)-E-1584) are associated with higher TGH and confer a higher likelihood of developing GDM. The impaired response of TRPM6((VI)-I-1393) and TRPM6((KE)-E-1584) to insulin represents a unique molecular pathway leading to GDM where the defect is located in TRPM6.
KW  - kidney
KW  - distal convoluted tubule
KW  - transient receptor potential
KW  - vesicular trafficking
Y1  - 2012
U6  - https://doi.org/10.1073/pnas.1113811109
SN  - 0027-8424
VL  - 109
IS  - 28
SP  - 11324
EP  - 11329
PB  - National Acad. of Sciences
CY  - Washington
ER  - 
TY  - JOUR
A1  - Li, Jian
A1  - Wang, Zi-Neng
A1  - Chen, You-Peng
A1  - Dong, Yun-Peng
A1  - Shuai, Han-Lin
A1  - Xiao, Xiao-Min
A1  - Reichetzeder, Christoph
A1  - Hocher, Berthold
T1  - Late gestational maternal serum cortisol is inversely associated with fetal brain growth
JF  - Neuroscience & biobehavioral reviews : official journal of the International Behavioral Neuroscience Society
N2  - To analyze the association between fetal brain growth and late gestational blood serum cortisol in normal pregnancy.Blood total cortisol was quantified at delivery in 432 Chinese mother/child pairs. Key inclusion criteria of the cohort were: no structural anomalies of the newborn, singleton pregnancy, no alcohol abuse, no drug abuse or history of smoking no hypertensive disorders and no impairment of glucose tolerance and no use of steroid medication during pregnancy. Differential ultrasound examination of the fetal body was done in early (gestational day 89.95 +/- 7.31), middle (gestational day 160.17 16.12) and late pregnancy (gestational day 268.89 +/- 12.42). Newborn's cortisol was not correlated with any of the ultrasound measurements during pregnancy nor with birth weight. Multivariable regression analysis, considering timing of the ultrasound examination, the child's sex, maternal BMI, maternal age, maternal body weight at delivery, the timing of cortisol measurement and maternal uterine contraction states, revealed that maternal serum total cortisol was significantly negative correlated with ultrasound parameters describing the fetal brain: late biparietal diameter (R-2 =0.512, p =0.009), late head circumference (R-2 = 0.498, p= 0.001), middle biparietal diameter (R-2= 0.819, p = 0.013), middle cerebellum transverse diameter R-2 = 0.76, p= 0.014) and early biparietal diameter(R-2 = 0.819, p = 0.013). The same analysis revealed that birth weight as well as ultrasound parameters such as abdominal circumference and femur length were not correlated to maternal cortisol levels.
 In conclusion, our study demonstrates that maternal cortisol secretion within physiological ranges may be inversely correlated to fetal brain growth but not to birth weight. It remains to be demonstrated whether maternal cortisol secretion negatively influencing fetal brain growth translates to adverse neurological outcomes in later life.
KW  - Brain development
KW  - Fetal programming
KW  - Cortisol Maternal cortisol
KW  - Head circumference
KW  - Biparietal diameter
Y1  - 2012
U6  - https://doi.org/10.1016/j.neubiorev.2011.12.006
SN  - 0149-7634
VL  - 36
IS  - 3
SP  - 1085
EP  - 1092
PB  - Elsevier
CY  - Oxford
ER  -