Filter

Refine by Access

Refine by Date

—
  • Print
  • Save

Search Results

You are looking at 1 - 10 of 13 items for

  • Author: Jürgen Kratzsch x
  • Refine by Access: All content x
Clear All Modify Search
Restricted access

Growth hormone-binding protein-related immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration

Jürgen Kratzsch, Werner F Blum, Manfred Ventz, Thomas Selisko, Gerd Birkenmeyer, and Eberhard Keller

Kratzsch J. Blum WF, Ventz M, Selisko T, Birkenmeyer G, Keller E. Growth hormone-binding proteinrelated immunoreactivity in the serum of patients with acromegaly is regulated inversely by growth hormone concentration. Eur J Endocrinol 1994;132:306–12. ISSN 0804–4643

In this report we describe a newly developed radioimmunoassay (RIA) for the determination of the high-affinity growth hormone-binding protein (GHBP) in human blood. Using this RIA for the measurement of GHBP in serum of 29 patients with acromegaly, decreased concentrations were found compared to the normal range, depending on the activity of the disease. Growth hormonebinding protein was correlated inversely to log GH (r = −0.7, p < 0.001). A weaker relationship was shown between the GHBP activity determined in a functional assay based on charcoal separation and log GH (r = −0.51, p< 0.01). While insulin-like growth factor I (IGF-I) and IGF binding protein 3 (IGFBP-3) were correlated directly to log GH (r = 0.77 and r = 0.66, p < 0.001), an inverse and weaker relationship was evident between GHBP measured by RIA and IGF-I or IGFBP-3 (r = −0.61 and r = −0.57,p < 0.01). In contrast, no correlation could be detected between data of the functional GHBP assay and IGF-I or IGFBP-3, These results suggest, that: (1) in patients with acromegaly the GH receptor density in tissue reflected by the GHBP serum levels seems to be down-regulated, depending on the increased GH level; (2) low GHBP concentrations indicate an active disease in acromegaly and may be of diagnostic interest; (3) presuming that the GH receptor density is related to GH sensitivity, the variation of GH sensitivity is less important for IGF-I and IGFBP-3 production than the circulating GH concentration, at least in the situation of acromegaly; (4) because endogenous GH does not interfere in that assay, the RIA provides a valuable tool for the investigation of regulations between GH, GHBP and the GH receptor, especially in patients with acromegaly. The GHBP levels may be used as a sensitive parameter of GH oversecretion and tissue sensitivity to this hormone.

Jürgen Kratzsch, Inst. Clin. Chem., University of Leipzig, Paul-List-Str. 13–15, D-04103 Leipzig, Germany

Free access

Elevated serum levels of adiponectin in children, adolescents and young adults with type 1 diabetes and the impact of age, gender, body mass index and metabolic control: a longitudinal study

Angela Galler, Götz Gelbrich, Jürgen Kratzsch, Nicole Noack, Thomas Kapellen, and Wieland Kiess

Objective: Adiponectin plays an important role in pathophysiology of obesity, type 2 diabetes and cardiovascular disease. The aim of this study was to determine adiponectin concentrations in children and adolescents with type 1 diabetes in a longitudinal manner and to study the impact of age, gender, body mass index (BMI) and metabolic control.

Research design and methods: In this study, 88 children and adolescents with type 1 diabetes were followed longitudinally. At baseline and during follow-up, serum levels of adiponectin were measured by enzyme-linked immunoassay and correlated with clinical data, HbA1c and lipids. Healthy children (n = 259) were chosen as a control group.

Results: Serum adiponectin levels were significantly higher in children with type 1 diabetes compared with healthy children (13.1 vs 9.1 μg/ml at baseline, P < 0.001). Adiponectin concentrations inversely correlated with BMI s.d.s (P < 0.001). No significant difference of adiponectin levels regarding gender, diabetes duration or HbA1c was seen. Adiponectin concentrations decreased in males with type 1 diabetes during puberty (P = 0.03) while there was no significant change in females. In a subgroup of patients with new onset type 1 diabetes, adiponectin concentrations were not different from adiponectin levels in control subjects but increased during follow-up (P = 0.007). Stepwise multiple regression analysis showed that most important predictors of adiponectin levels in type 1 diabetes at the end of the study were adiponectin concentration at baseline (β = 0.574, P < 0.001) and BMI s.d.s (β = −0.302, P = 0.001, r 2 = 0.56).

Conclusions: Children and adolescents with type 1 diabetes have BMI-dependent elevated serum concentrations of adiponectin compared with healthy children.

Free access

Serum levels of adipocyte fatty acid binding protein are increased in gestational diabetes mellitus

Susan Kralisch, Holger Stepan, Jürgen Kratzsch, Michael Verlohren, Hans-Joachim Verlohren, Kathrin Drynda, Ulrike Lössner, Matthias Blüher, Michael Stumvoll, and Mathias Fasshauer

Objective

Adipocyte fatty acid binding protein (AFABP) was recently introduced as a novel adipokine, serum levels of which independently correlate with the development of the metabolic syndrome and cardiovascular disease in humans. In the current study, we investigated serum concentrations of AFABP in patients with gestational diabetes mellitus (GDM) as compared with healthy pregnant controls matched for gestational age and fasting insulin.

Design and methods

AFABP was determined by ELISA in controls (n=80) and GDM patients (n=40) and correlated to clinical and biochemical measures of renal function, glucose and lipid metabolism, as well as inflammation, in both groups.

Results

Median serum AFABP concentrations were significantly elevated in subjects with GDM (22.9 μg/l) as compared with healthy pregnant controls (18.3 μg/l; P<0.05). Furthermore, GDM was independently associated with AFABP concentrations in multiple regression analysis (P<0.05). In addition, markers of adiposity (body mass index, serum leptin), triglycerides and serum creatinine were independently associated with circulating AFABP (P<0.05).

Conclusions

Maternal AFABP concentrations are significantly increased in GDM. The adipokine might contribute to the increased metabolic and cardiovascular risk of the disease.

Free access

Betatrophin levels are increased in women with gestational diabetes mellitus compared to healthy pregnant controls

Thomas Ebert, Susan Kralisch, Ulrike Wurst, Ulrike Lössner, Jürgen Kratzsch, Matthias Blüher, Michael Stumvoll, Anke Tönjes, and Mathias Fasshauer

Objective

Betatrophin has recently been introduced as a novel adipokine/hepatokine, which promotes pancreatic β cell proliferation and improves glucose tolerance in several mouse models of insulin resistance. However, regulation of betatrophin in gestational diabetes mellitus (GDM), as well as its association with markers of obesity, such as glucose and lipid metabolism, inflammation, and renal function, have not been elucidated.

Design and methods

Circulating betatrophin was quantified in 74 women with GDM and 74 healthy and gestational age-matched controls by ELISA. In a subset of the study population comprising of 85 patients (41 previous controls, 44 previous women with GDM), postpartum betatrophin levels were measured in a follow-up study.

Results

Median (interquartile range) serum betatrophin levels were higher in women with GDM (1.79 (0.53) μg/l) as compared to non-diabetic pregnant controls (1.58 (0.44) μg/l) (P=0.002). In multivariate analysis, GDM status was an independent and positive predictor of circulating betatrophin (P=0.001). Furthermore, betatrophin levels were significantly higher during gestation (1.70 (0.53) μg/l) as compared to postpartum levels (1.55 (0.66) μg/l) (P=0.028). Moreover, postpartum irisin remained a positive and independent predictor of postpartum betatrophin concentrations.

Conclusions

Women with GDM have significantly higher betatrophin levels as compared to healthy pregnant controls and GDM status positively predicts circulating betatrophin. Furthermore, postpartum levels are significantly lower as compared to betatrophin concentrations during pregnancy. Moreover, irisin is a significant predictor of postpartum betatrophin levels.

Free access

Genome-wide association and transcriptome analysis suggests total serum ghrelin to be linked with GFRAL

Dirk Alexander Wittekind, Markus Scholz, Jürgen Kratzsch, Markus Löffler, Katrin Horn, Holger Kirsten, Veronica Witte, Arno Villringer, and Michael Kluge

Objective

Ghrelin is an orexigenic peptide hormone involved in the regulation of energy homeostasis, food intake and glucose metabolism. Serum levels increase anticipating a meal and fall afterwards. Underlying genetic mechanisms of the ghrelin secretion are unknown.

Methods

Total serum ghrelin was measured in 1501 subjects selected from the population-based LIFE-ADULT-sample after an overnight fast. A genome-wide association study (GWAS) was performed. Gene-based expression association analyses (transcriptome-wide association study (TWAS)) are statistical tests associating genetically predicted expression to a certain trait and were done using MetaXcan.

Results

In the GWAS, three loci reached genome-wide significance: the WW-domain containing the oxidoreductase-gene (WWOX; P = 1.80E-10) on chromosome 16q23.3-24.1 (SNP: rs76823993); the contactin-associated protein-like 2 gene (CNTNAP2; P = 9.0E-9) on chromosome 7q35-q36 (SNP: rs192092592) and the ghrelin And obestatin prepropeptide gene (GHRL; P = 2.72E-8) on chromosome 3p25.3 (SNP: rs143729751). In the TWAS, the three genes where the expression was strongest associated with serum ghrelin levels was the ribosomal protein L36 (RPL36; P = 1.3E-06, FDR = 0.011, positively correlated), AP1B1 (P = 1.1E-5, FDR = 0.048, negatively correlated) and the GDNF family receptor alpha like (GFRAL), receptor of the anorexigenic growth differentiation factor-15 (GDF15), (P = 1.8E-05, FDR = 0.15, also negatively correlated).

Conclusions

The three genome-wide significant genetic loci from the GWA and the genes identified in the TWA are functionally plausible and should initiate further research.

Free access

Circulating high-molecular-weight adiponectin is upregulated in preeclampsia and is related to insulin sensitivity and renal function

Mathias Fasshauer, Theresa Waldeyer, Jeannette Seeger, Susanne Schrey, Thomas Ebert, Jürgen Kratzsch, Ulrike Lössner, Matthias Blüher, Michael Stumvoll, Renaldo Faber, and Holger Stepan

Objective

Preeclampsia (PE) is a serious cardiovascular complication in pregnancy which is associated with an increased future metabolic and cardiovascular risk for mother and newborn. Recently, a paradoxical upregulation of the insulin-sensitizing and anti-atherogenic adipokine adiponectin has been shown in PE. Furthermore, high-molecular-weight (HMW) adiponectin has been suggested as the biologically active form of this adipokine.

Design and methods

HMW adiponectin and total adiponectin serum concentrations were quantified by ELISA in PE (n=16) patients and pregnant control women without PE (n=20). Furthermore, HMW adiponectin and total adiponectin were correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation.

Results

Median maternal HMW adiponectin and total adiponectin levels were significantly and independently upregulated almost twofold in PE when compared with controls. HMW adiponectin and total adiponectin correlated positively with creatinine and negatively with fasting insulin in univariate and multivariate analyses.

Conclusions

We show that maternal HMW adiponectin and total adiponectin serum concentrations are significantly increased in PE and are positively associated with markers of insulin sensitivity and renal dysfunction. Adiponectin might be part of a physiological feedback mechanism improving insulin sensitivity and cardiovascular health in PE.

Free access

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

Thomas M K Völkl, Diemud Simm, Antje Körner, Wolfgang Rascher, Wieland Kiess, Jürgen Kratzsch, and Helmuth G Dörr

Objective

Congenital adrenal hyperplasia (CAH) patients are at a higher risk to develop obesity. The role of leptin in CAH is still controversial. Our study aimed to evaluate serum levels of leptin, the soluble leptin receptor (sOB-R), and the sOB-R: leptin molar ratios in a cohort of CAH children and adolescents, and their associations with clinical and metabolic parameters.

Methods

We studied 51 CAH patients, aged 5.6–19.6 years (median 11.8, n=30 females) cross-sectionally. All patients had genetically proven CAH and received standard steroid substitution therapy. Blood specimens were taken after overnight fasting between 0800 and 1000 h. For the analyses of leptin and sOB-R, matched pairs were built with healthy Caucasian patients for sex, Tanner stage (TS), chronologic age (CA), and body mass index (BMI).

Results

BMI and SDS were significantly elevated compared with the reference population. Leptin levels were not different between matched pairs, whereas sOB-R levels were significantly lower in CAH. Consequently, the sOB-R: leptin molar ratios were significantly decreased in CAH. Correlation analyses in CAH patients revealed significant relationship between leptin and CA, TS, BMI, and homeostasis model assessment of insulin resistance. Similar results were obtained for the matched control group. For sOB-R, we found no significant correlation for CA, TS, or BMI in CAH, but we did in the controls. There were significant correlations for androgens within the CAH group. Additional analyses revealed no correlation with steroid medication or metabolic control.

Conclusions

Our data show that an altered leptin axis with normal serum leptin concentrations but decreased sOB-R serum levels may contribute to the increased risk of overweight and obesity in CAH.

Free access

Effect of a 4 week physical training program on plasma concentrations of inflammatory markers in patients with abnormal glucose tolerance

Andreas Oberbach, Anke Tönjes, Nora Klöting, Mathias Fasshauer, Jürgen Kratzsch, Martin W Busse, Ralf Paschke, Michael Stumvoll, and Matthias Blüher

Objective: Subclinical chronic inflammation could be a unifying factor linking type 2 diabetes (T2D) and atherosclerosis. The beneficial effects of physical activity on a reduced risk of coronary heart disease could at least in part be mediated by improved markers of inflammation.

Research design and methods: The aim of this study was to determine the effect of 4 weeks of physical training on plasma concentrations of interleukin (IL)-6, C-reactive protein (CRP), adiponectin and IL-10 in 60 individuals with normal glucose tolerance, impaired glucose tolerance (IGT) or T2D.

Results: In patients with IGT and T2D, significant improvement in body fat, fitness level, glucose metabolism and insulin sensitivity after 4 weeks of physical training was associated with significantly improved plasma concentrations of adiponectin and CRP, but not IL-6. Regression analysis demonstrated only for the anti-inflammatory parameters adiponectin and IL-10 a significant relationship with the decrease in fasting plasma glucose, whereas changes in IL-6 and CRP were not significantly related to changes in fasting plasma glucose, body fat, maximal oxygen uptake, or insulin sensitivity. In a multivariate linear regression analysis, only changes in circulating adiponectin, fasting plasma glucose and percentage body fat were determinants of changes in insulin sensitivity.

Conclusions: Physical training was associated with a near normalization of adiponectin and CRP plasma concentrations in subjects with IGT and T2D. Increased insulin sensitivity after training was most strongly related to changes in adiponectin plasma concentrations, in fasting plasma glucose and percentage body fat, whereas changes in IL-6, IL-10 and CRP plasma concentrations did not significantly contribute to improved insulin sensitivity.

Free access

Serum levels of the myokine irisin in relation to metabolic and renal function

Thomas Ebert, Denise Focke, David Petroff, Ulrike Wurst, Judit Richter, Anette Bachmann, Ulrike Lössner, Susan Kralisch, Jürgen Kratzsch, Joachim Beige, Ingolf Bast, Matthias Anders, Matthias Blüher, Michael Stumvoll, and Mathias Fasshauer

Objective

Irisin has recently been introduced as a novel myokine which reverses visceral obesity and improves glucose metabolism in mice. However, regulation of irisin in humans in relation to renal and metabolic disease has not been comprehensively studied.

Design and methods

Serum irisin levels were quantified by ELISA and correlated with anthropometric and biochemical parameters of renal function, glucose and lipid metabolism, as well as inflammation, in 532 patients with stages 1–5 of chronic kidney disease (CKD).

Results

Median serum irisin levels adjusted for age, gender, and BMI significantly decreased with increasing CKD stage and lowest concentrations were seen in patients with CKD stage 5. Furthermore, irisin concentrations were associated with facets of the metabolic syndrome including diastolic blood pressure, markers of impaired glucose tolerance, and dyslipidemia in univariate analysis. Moreover, markers of renal function, e.g. glomerular filtration rate, and insulin resistance, e.g. homeostasis model assessment of insulin resistance, remained independently associated with circulating irisin levels in robust multivariate analysis.

Conclusions

We show that irisin serum concentrations decrease with increasing CKD stage and are independently and positively predicted by renal function and insulin resistance. The physiological relevance of our findings, as well as the factors contributing to irisin regulation in humans, needs to be further defined in future experiments.

Free access

Prospective evaluation of aldosterone LC-MS/MS-specific cutoffs for the saline infusion test

Charlotte Michaela Fries, Yoon Ju Bae, Nada Rayes, Benjamin Sandner, Berend Isermann, Michael Stumvoll, Valentina Fagotto, Martin Reincke, Martin Bidlingmaier, Vogel Mandy, Jürgen Kratzsch, and Wiebke Kristin Fenske

Objective

Liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) has become state of the art for the quantitative analysis of steroid hormones. Although method comparisons show that aldosterone measurement using LC-MS/MS yields considerably lower levels than immunoassays (IAs), method-specific cutoff values for primary aldosteronism (PA) are largely missing. Objective of this study was to analyze the diagnostic accuracy of proposed LC-MS/MS-specific cutoff values for the saline infusion test (SIT).

Design and methods

From 2016 to 2019, 104 consecutive patients suspected of PA underwent the SIT and captopril challenge test in the tertiary medical center at the University Hospital of Leipzig, Germany. Patients with positive case confirmation underwent adrenal imaging and adrenal venous sampling for subtype classification.

Results

Overall, proposed assay-specific PACLC-MS/MS cutoff values for the SIT achieved higher diagnostic accuracy than established PACIA values with a sensitivity and specificity of 87.5% (95% CI: 71.0–96.5) and 97% (95% CI: 89.6–99.6) for a cutoff of 120 pmol/L and 93.8% (95% CI: 79.2–99.2) and 92.5% (95% CI: 83.4–97.5) for a cutoff of 94 pmol/L. The most accurate post-SIT PACLC-MS/MS cutoff value in this study was 83 pmol/L, yielding a sensitivity and specificity of 96.9% (95% CI: 83.8–99.9) and 92.5% (95% CI: 83.4–97.5), respectively.

Conclusions

The present data confirm the need for the implication of lower method-specific aldosterone cutoff values for the diagnosis of PA with LC-MS/MS based aldosterone measurement.