Response to Immunization against SARS-CoV-2 and Risk of Omicron Infection in Dialysis Patients: A Prospective Cohort Study.

It is not well established to what extent previous immunizations offer protection against infections with the SARS-CoV-2 Omicron variant in dialysis patients. We aimed to define the relevant humoral response in dialysis patients using a SARS-CoV-2 IgG chemiluminescence microparticle immunoassay (CMIA) compared to the activity of neutralizing antibodies assessed by a virus neutralization test. Next, we aimed to determine differences in humoral and cellular response levels over time among patients infected or not infected by the Omicron variant of SARS-CoV-2. Immunological parameters of cellular and humoral response to SARS-CoV-2 were analyzed at baseline and after 3 (T3), 6 (T6) and 14 months (T14). In this monocentric cohort study, we followed 110 dialysis patients (mean age 68.4 ± 13.7 years, 60.9% male) for a median of 545 days. We determined an anti-SARS-CoV-2 IgG level of 56.7 BAU/mL as an ideal cut-off value with a J-index of 90.7. Patients infected during the Omicron era had significantly lower (p < 0.001) mean antibody levels at T0 (3.5 vs. 111.2 BAU/mL), T3 (269.8 vs. 699.8 BAU/mL) and T6 (260.2 vs. 513.9 BAU/mL) than patients without Omicron infection. Patients who developed higher antibody levels at the time of the basic immunizations were less likely to become infected with SARS-CoV-2 during the Omicron era. There is a need to adjust the cut-off values for anti-SARS-CoV-2 IgG levels in dialysis patients.

Antigen-Specific Immunoadsorption With the Glycosorb® ABO Immunoadsorption System as a Novel Treatment Modality in Pure Red Cell Aplasia Following Major and Bidirectional ABO-Incompatible Allogeneic Hematopoietic Stem Cell Transplantation.

Pure red cell aplasia (PRCA) after ABO-incompatible allogeneic hematopoietic stem cell transplantation (HSCT) is caused by persisting host-derived isohemagglutinins directed against donor red blood cell (RBC) antigens. ABO antigen-specific immunoadsorption (ABO-IA) with Glycosorb®, commonly used for desensitization therapy in ABO-incompatible living donor renal transplantation, specifically eliminates circulating isohemagglutinins and might represent a novel treatment option for post-HSCT PRCA. In this prospective observational (n = 3) and retrospective (n = 3) analysis of six adult HSCT-recipients with PRCA, ABO-IA was initiated at 159 (range: 104-186) days following HSCT. The median treatment frequency was 4.5 (range: 3.9-5.5) sessions/week. ABO-IA-treatment led to a continuous decrease in isohemagglutinin titers. Reticulocytes increased to ≥30 G/L after 17.5 (range: 4-37) immunoadsorption sessions over 28.5 (range: 6-49) days and continued to rise after that. By the end of the 3-month follow-up period after discontinuation of ABO-IA, all patients showed a sustained remission of PRCA and were independent of erythropoietin-stimulating agents and transfusions. No case of infection or graft-versus-host disease was observed. After a median follow-up of 22.03 (range: 6.08-149.00) months after ABO-IA-treatment, all patients were alive and showed a stable RBC engraftment of the donor blood group. Our data provide the first evidence for ABO-IA as an effective treatment for post-HSCT PRCA.

Diagnostic and Prognostic Value of Soluble Urokinase-type Plasminogen Activator Receptor (suPAR) in Focal Segmental Glomerulosclerosis and Impact of Detection Method.

The plasma soluble urokinase-type plasminogen activator receptor (suPAR) is a biomarker for focal segmental glomerulosclerosis (FSGS), but its value is under discussion because of ambiguous results arising from different ELISA methods in previous studies. The aim of this study was to compare diagnostic performance of two leading suPAR ELISA kits and examine four objectives in 146 subjects: (1) plasma suPAR levels according to glomerular disease (primary, secondary and recurrent FSGS after kidney transplantation, other glomerulonephritis) and in healthy controls; (2) suPAR levels based on glomerular filtration rate; (3) sensitivity and specificity of suPAR for FSGS diagnosis and determination of optimal cut-offs; (4) suPAR as prognostic tool. Patients with FSGS showed significant higher suPAR values than patients with other glomerulonephritis and healthy individuals. This applied to subjects with and without chronic kidney disease. Although both suPARnostic™ assay and Quantikine Human uPAR ELISA Kit exerted high sensitivity and specificity for FSGS diagnosis, their cut-off values of 4.644 ng/mL and 2.789 ng/mL were significantly different. Higher suPAR was furthermore predictive for progression to end-stage renal disease. In summary, suPAR values must be interpreted in the context of population and test methods used. Knowing test specific cut-offs makes suPAR a valuable biomarker for FSGS.

Are hypothyroidism and hypogonadism clinically relevant in patients with malignant gliomas? A longitudinal trial in patients with glioma.

BACKGROUND: So far, the development and course of therapy-induced deficiencies in hypothalamic-pituitary hormones in adult patients with malignant gliomas has not received much attention. However, such deficiencies may impact patient's quality of life substantially. METHODS: In this monocentric longitudinal trial, we examined hormonal levels of TSH, T3, T4, fT3, fT4, FSH, LH, testosterone, estradiol and prolactin in patients with malignant high grade gliomas before the start of radiochemotherapy (RCT), at the end of RCT and then every three months for newly diagnosed patients and every six months in patients diagnosed more than two years before study inclusion. Growth hormone was not measured in this trial. RESULTS: 436 patients (198 female, 238 male) with high-grade gliomas, aged 19-83 years (median 50 years), were included in this study. Low levels of thyroid hormones were observed in around 10% of patients within the first six months of follow up and increasingly after 36 months. Half of premenopausal women at study entry developed premature menopause, 35% showed hyperprolactinemia. Low testosterone levels were measured in 37% of men aged less than 50 years and in 35/63 (55%) of men aged 50 years or older. DISCUSSION: The results of this study show that a significant percentage of patients with malignant gliomas develop hormonal deficiencies mandating regular clinical follow up, state of the art counseling and if clinically necessary substitution therapy.

Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters.

Catheter-related infections and dysfunction are the main catheter complications causing morbidity and mortality in hemodialysis patients. However, there are no consistent data for the choice of catheter lock solutions for tunneled hemodialysis lines. In this prospective, multicenter, randomized, controlled trial, two lock regimens using three commercial catheter lock solutions were compared in 106 hemodialysis patients with a newly inserted tunneled central catheter. In the taurolidine group, TauroLock™-Hep500 was used twice per week and TauroLock™-U25,000 once a week. In the citrate group, a four percent citrate solution was used after each dialysis. Both groups were compared regarding catheter-related infections, catheter dysfunction, and costs. Over a period of 15,690 catheter days, six catheter-related infections occurred in six of 52 patients in the taurolidine group, but 18 occurred in 13 of 54 patients in the citrate group, corresponding to 0.67 and 2.7 episodes of catheter-related infections per 1000 catheter days, respectively (Incidence Rate Ratio 0.25, 95% confidence interval, 0.09 to 0.63). Catheter dysfunction rates were significantly lower in the taurolidine group (18.7 vs. 44.3/1000 catheter days) and alteplase rescue significantly more frequent in the citrate group (9.8 vs. 3.8/1000 catheter days). These differences provided significant catheter-related cost savings of 43% in the taurolidine group vs. citrate group when overall expenses per patient and year were compared. Thus, use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient.

A Randomized Trial of Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection.

Late antibody-mediated rejection (ABMR) is a leading cause of kidney allograft failure. Uncontrolled studies have suggested efficacy of the proteasome inhibitor bortezomib, but no systematic trial has been undertaken to support its use in ABMR. In this randomized, placebo-controlled trial (the Bortezomib in Late Antibody-Mediated Kidney Transplant Rejection [BORTEJECT] Trial), we investigated whether two cycles of bortezomib (each cycle: 1.3 mg/m2 intravenously on days 1, 4, 8, and 11) prevent GFR decline by halting the progression of late donor-specific antibody (DSA)-positive ABMR. Forty-four DSA-positive kidney transplant recipients with characteristic ABMR morphology (median time after transplant, 5.0 years; pretransplant DSA documented in 19 recipients), who were identified on cross-sectional screening of 741 patients, were randomly assigned to receive bortezomib (n=21) or placebo (n=23). The 0.5-ml/min per 1.73 m2 per year (95% confidence interval, -4.8 to 5.8) difference detected between bortezomib and placebo in eGFR slope (primary end point) was not significant (P=0.86). We detected no significant differences between bortezomib- and placebo-treated groups in median measured GFR at 24 months (33 versus 42 ml/min per 1.73 m2; P=0.31), 2-year graft survival (81% versus 96%; P=0.12), urinary protein concentration, DSA levels, or morphologic or molecular rejection phenotypes in 24-month follow-up biopsy specimens. Bortezomib, however, associated with gastrointestinal and hematologic toxicity. In conclusion, our trial failed to show that bortezomib prevents GFR loss, improves histologic or molecular disease features, or reduces DSA, despite significant toxicity. Our results reinforce the need for systematic trials to dissect the efficiency and safety of new treatments for late ABMR.

Immunoadsorption in Autoimmune Diseases Affecting the Kidney.

Autoantibodies play an important role in the pathophysiology of renal involvement in systemic autoimmune diseases, such as systemic lupus erythematosus (SLE), systemic vasculitis, and anti-glomerular basement membrane disease (or Goodpasture syndrome). Direct removal of autoantibodies therefore has been tried in various ways, first by plasma exchange. Today, immunoadsorption is the extracorporeal method that most effectively removes (pathogenic) immune complexes and antibodies. Although past data have shown efficacy and biocompatibility of immunoadsorption in (renal) SLE, it is still an experimental and expensive procedure, and evidence from randomized controlled trials is needed. Nevertheless, immunoadsorption is being used as a rescue therapy in life-threatening situations of SLE patients because of its fast mode of action and its acceptable safety profile. In granulomatosis with polyangiitis (GPA) (or Wegener's granulomatosis), microscopic polyangiitis (MPA), and anti-glomerular basement membrane disease, the current standard is plasma exchange. Immunoadsorption, which probably would reduce the autoantibody burden more effectively, might be an even better more effective option, but sufficient evidence is lacking.

A case report of septic shock syndrome caused by S. pneumoniae in an immunocompromised patient despite of vaccination.

BACKGROUND AND CASE PRESENTATION: We report a case of septic shock syndrome caused by Streptococcus pneumoniae in a patient who had undergone splenectomy due to an autoimmune lymphoproliferative syndrome (ALPS), which is characterized as a dysfunction of immunoregulation. Although the patient was vaccinated with a conjugated polysaccharide vaccine after the splenectomy, he was still susceptible to S. pneumoniae infection, because the isolated serovar (24F), a serovar long thought to be apathogenic, is not covered by any vaccine currently approved, neither a conjugated nor an unconjugated polysaccharide one. CONCLUSIONS: This case demonstrates that, due to presence of different serovars, also infections with bacteria against which patients are vaccinated have to be considered as differential diagnosis. Although vaccine development has extended the coverage of S. pneumoniae from 7 to 23 serovars within recent years, there is still demand for novel vaccines which can provide broader protection also against so-thought "apathogenic" strains, especially for groups at high risk.

Conversion from Tacrolimus to Cyclosporine A Improves Glucose Tolerance in HCV-Positive Renal Transplant Recipients.

BACKGROUND: Calcineurin-inhibitors and hepatitis C virus (HCV) infection increase the risk of post-transplant diabetes mellitus. Chronic HCV infection promotes insulin resistance rather than beta-cell dysfunction. The objective was to elucidate whether a conversion from tacrolimus to cyclosporine A affects fasting and/or dynamic insulin sensitivity, insulin secretion or all in HCV-positive renal transplant recipients. METHODS: In this prospective, single-center study 10 HCV-positive renal transplant recipients underwent 2h-75g-oral glucose tolerance tests before and three months after the conversion of immunosuppression from tacrolimus to cyclosporine A. Established oral glucose tolerance test-based parameters of fasting and dynamic insulin sensitivity and insulin secretion were calculated. Data are expressed as median (IQR). RESULTS: After conversion, both fasting and challenged glucose levels decreased significantly. This was mainly attributable to a significant amelioration of post-prandial dynamic glucose sensitivity as measured by the oral glucose sensitivity-index OGIS [422.17 (370.82-441.92) vs. 468.80 (414.27-488.57) mL/min/m2, p = 0.005), which also resulted in significant improvements of the disposition index (p = 0.017) and adaptation index (p = 0.017) as markers of overall glucose tolerance and beta-cell function. Fasting insulin sensitivity (p = 0.721), insulinogenic index as marker of first-phase insulin secretion [0.064 (0.032-0.106) vs. 0.083 (0.054-0.144) nmol/mmol, p = 0.093) and hepatic insulin extraction (p = 0.646) remained unaltered. No changes of plasma HCV-RNA levels (p = 0.285) or liver stiffness (hepatic fibrosis and necroinflammation, p = 0.463) were observed after the conversion of immunosuppression. CONCLUSIONS: HCV-positive renal transplant recipients show significantly improved glucose-stimulated insulin sensitivity and overall glucose tolerance after conversion from tacrolimus to cyclosporine A. Considering the HCV-induced insulin resistance, HCV-positive renal transplant recipients may benefit from a cyclosporine A-based immunosuppressive regimen. TRIAL REGISTRATION: ClinicalTrials.gov NCT02108301.

Effect of chronic kidney disease on macrophage cholesterol efflux.

AIMS: Patients with chronic kidney disease (CKD) have a high risk to develop atherosclerosis. The capacity of high-density lipoproteins (HDL) or serum to accept cholesterol from macrophages and the capacity of macrophages to export excess cholesterol are critical for the atheroprotective role of reverse cholesterol transport. HDL cholesterol acceptor capacity was reported to be decreased in middle aged hemodialysis patients, but the role of confounding factors remains unclear. MAIN METHODS: We measured the cholesterol acceptor capacity (CAC) of HDL or serum in 12 pediatric and 17 young adult patients with CKD stages 3-5, 14 young adult hemodialysis patients and 15 adult renal transplant recipients without associated diseases and matched controls using THP-1 macrophages. Moreover we studied the cholesterol export capacity (CEC) of patients' monocyte-derived macrophages (HMDMs) to control serum or HDL. KEY FINDINGS: In adults with CKD stages 3-5 serum CAC was slightly increased, whereas CEC of HMDMs was unaltered in both, adult and pediatric patients. In hemodialysis patients, however, serum CAC was markedly reduced to 85±11% of control (p<0.001), presumably due to low serum apolipoprotein A-I. Interestingly, CEC of HMDMs from dialysis patients was increased. In transplant patients no alterations were found. SIGNIFICANCE: CKD without hemodialysis does not reduce cholesterol export from macrophages. Hemodialysis patients might benefit from therapies aiming to restore serum CAC by increasing apolipoprotein A-I. The enhanced export of cholesterol by HMDMs from dialysis patients may represent an adaptive response.

Urine osmolarity and risk of dialysis initiation in a chronic kidney disease cohort--a possible titration target?

BACKGROUND: Increasing evidence is linking fluid intake, vasopressin suppression and osmotic control with chronic kidney disease progression. Interestingly, the association between urine volume, urine osmolarity and risk of dialysis initiation has not been studied in chronic kidney disease patients before. OBJECTIVE: To study the relationship between urine volume, urine osmolarity and the risk of initiating dialysis in chronic kidney disease. DESIGN: In a retrospective cohort analysis of 273 patients with chronic kidney disease stage 1-4 we assessed the association between urine volume, urine osmolarity and the risk of dialysis by a multivariate proportional sub-distribution hazards model for competing risk data according to Fine and Gray. Co-variables were selected via the purposeful selection algorithm. RESULTS: Dialysis was reached in 105 patients over a median follow-up period of 92 months. After adjustment for age, baseline creatinine clearance, other risk factors and diuretics, a higher risk for initiation of dialysis was found in patients with higher urine osmolarity. The adjusted sub-distribution hazard ratio for initiation of dialysis was 2.04 (95% confidence interval, 1.06 to 3.92) for each doubling of urine osmolarity. After 72 months, the estimated adjusted cumulative incidence probabilities of dialysis were 15%, 24%, and 34% in patients with a baseline urine osmolarity of 315, 510, and 775 mosm/L, respectively. CONCLUSIONS: We conclude that higher urine osmolarity is associated with a higher risk of initiating dialysis. As urine osmolarity is a potentially modifiable risk factor, it thus deserves further, prospective research as a potential target in chronic kidney disease progression.

Lipoprotein(a) is not related to markers of insulin resistance in pregnancy.

BACKGROUND: Dyslipidemia, a major risk factor for cardiovascular disease is a common finding in patients with type 2 diabetes and among women with gestational diabetes. Elevated levels of lipoprotein(a) [Lp(a)] are linked to increased risk of cardiovascular disease. However, its relationship with insulin resistance, type 2 diabetes and gestational diabetes is controversial and unproven. Here we aimed to clarify whether Lp(a) levels are associated with insulin sensitivity in pregnancy. METHODS: Sixty-four women with gestational diabetes and 165 with normal glucose tolerance were enrolled in the study. Fasting Lp(a) serum levels were measured in all women at 24-28 weeks of gestation. RESULTS: In pregnancy, there was no significant difference in serum Lp(a) concentrations between the two groups. Its level did not correlate with markers of insulin resistance (HOMA-IR), insulin sensitivity (HOMA-S%), pancreatic beta-cell function (HOMA-B%) and insulin sensitivity in dynamic conditions (OGIS). In addition, fasting glucose and insulin levels and those throughout an oral glucose tolerance test were independent of Lp(a) concentrations in our study group. CONCLUSIONS: Lp(a) levels in pregnant women do not differ with respect to the presence or absence of gestational diabetes. Although influenced by some components of the lipid profile, such as triglycerides and HDL-C, insulin resistance in pregnancy is not affected by Lp(a).

Relationship of pentraxin 3 with insulin sensitivity in gestational diabetes.

BACKGROUND: Pentraxin 3 (PTX3) is a cytokine-inducible molecule expressed in different tissues, the levels of which increase in a response to a variety of inflammatory conditions. Recently, it has been linked to the serum glucose levels and some comorbidities in type 2 diabetes. MATERIALS AND METHODS: Here, we aimed to investigate the role of PTX3 in gestational diabetes mellitus (GDM), which is considered a forerunner of type 2 diabetes. Fasting PTX3 serum levels were measured in 90 women [45 GDM, 45 normal glucose tolerance (NGT)] during pregnancy. In addition, PTX3 was measured during a 2 h, 75 g oral glucose tolerance test (OGTT) in 20 women (10 GDM, 10 NGT) at 24-28 weeks of gestation and in 16 of them after delivery (10GDM, 6 NGT). RESULTS: A continuous increase in PTX3 levels was observed during the OGTT and reached in the GDM group a significant difference after 120 min compared with baseline (P < 0·05). Additionally, a rise in the PTX3 concentration was significantly higher in the GDM- compared with the NGT group, 120 min after glucose challenge (P < 0·01). During pregnancy, serum glucose and C-peptide were positively correlated with the PTX3 levels in the whole study group, whereas a negative association was found with the insulin sensitivity parameters QUICKI and OGIS. CONCLUSIONS: Dependence of PTX3 on serum glucose levels was more pronounced in women with GDM than in the NGT group. This notion together with its inverse relation to the parameters of insulin sensitivity, suggests a potential involvement of PTX3 in GDM pathology.

Circulating progranulin levels in women with gestational diabetes mellitus and healthy controls during and after pregnancy.

OBJECTIVE: Progranulin (PGRN) was recently introduced as a novel marker of chronic inflammatory response in obesity and type 2 diabetes capable of directly affecting the insulin signaling pathway. This study aimed to investigate the role of PGRN in gestational diabetes mellitus (GDM), which is regarded as a model for early type 2 diabetes. METHODS: PGRN serum levels were measured in 90 pregnant women (45 GDM and 45 normal glucose tolerance (NGT)). In addition, PGRN was measured during a 2-h, 75 g oral glucose tolerance test in 20 pregnant women (ten GDM and ten NGT) and in 16 of them post partum (ten GDM and six NGT). RESULTS: PGRN concentrations were significantly higher in pregnant women compared with post partum levels (536.79 ± 31.81 vs 241.53 ± 8.86, P<0.001). Multivariate regression analyses showed a strong positive correlation of PGRN with estrogen and progesterone. The insulinogenic index, a marker of early insulin secretion, displayed a positive correlation with PGRN, both during and after pregnancy (R=0.47, P=0.034; R=0.63, P=0.012). HbA1c and the oral glucose insulin sensitivity index showed significant post partum associations with PGRN (R=0.43, P=0.049; R=-0.65, P=0.009). CONCLUSIONS: PGRN concentrations are markedly lower after pregnancy regardless of the gestational glucose tolerance state. PGRN levels per se do not discriminate between mild GDM and NGT in pregnant women. Therefore, the development of GDM appears to be due to impaired ß-cell function that is not related to PGRN effect.

CTX (crosslaps) rather than osteopontin is associated with disturbed glucose metabolism in gestational diabetes.

OBJECTIVE: Reciprocal interaction between bone and glucose metabolism might play a pivotal role in the development of type 2 diabetes. We recently demonstrated that osteocalcin is increased in women with gestational diabetes (GDM) compared to healthy pregnant women and related to enhanced insulin secretion. Here, we aimed to investigate the role of the bone resorption marker CTX and osteopontin (OPN), a key molecule in subclinical inflammation underlying insulin resistance, in gestational diabetes. METHODS: Insulin sensitivity and secretion (derived from OGTT) as well as CTX and osteopontin were investigated in 26 GDM and 52 women with normal glucose tolerance during pregnancy [CON] between 24th and 28th gestational weeks; 24 women also underwent postpartum examination. RESULTS: CTX was significantly higher in GDM compared to CON (0.44±0.20 vs.0.28±0.12 ng/ml, p<.0001) and positively correlated with osteocalcin (R = 0.64, p<.0001) and parameters of insulin secretion. Osteopontin plasma concentrations were decreased in GDM compared to CON (28.81±22.12 vs.37.68±19.63 ng/ml, p = 0.04), and did not show any relation to insulin secretion or sensitivity, but were significantly correlated with CRP (R = 0.3, p<0.007) and liver enzymes. Twelve weeks after delivery CTX and OPN were increased compared to pregnancy (both p<.0001) and did not differ between GDM and CON. CONCLUSION: Our findings support the idea of a tight regulation between bone and glucose metabolism, and suggest, that less curbed CTX during pregnancy might be involved in osteocalcin-mediated amelioration of insulin secretion in GDM. On the other hand, osteopontin was unrelated to insulin resistance in GDM, but associated with inflammatory markers and liver enzymes in all women.

Transcription factor 7-like 2 gene polymorphisms and gestational diabetes mellitus.

OBJECTIVE: Transcription factor 7-like 2 (TCF7L2) gene polymorphisms were shown to be associated with insulin resistance. We examined two single nucleotide exchanges in this gene in women with gestational diabetes mellitus (GDM) and in women with normal glucose tolerance. METHODS: A total of 1800 unselected women were prospectively screened for GDM by oral glucose tolerance test (OGTT) between 24 and 28 weeks of gestation. Two hundred and fifty Caucasian women of this collective, 125 patients with pathological OGTT and 125 patients with normal glucose tolerance were randomly selected. DNA samples were isolated and TCF7L2 gene polymorphisms (TCF7L2rs12255372 and TCF7L2rs7903146) were analyzed. RESULTS: Women with GDM were significantly older (30.1 ± 3.4 years vs. 28.2 ± 4.8 years, p = 0.01), had a significantly higher body mass index (26.4 kg/m(2); interquartile range: 23.33-31.19 vs. 24.6 kg/m(2); interquartile range: 21.05-27.28, p = 0.02) and were significantly more often homozygous for the T allele of TCF7L2rs12255372 (17.2% vs. 2.6%, p = 0.002) than patients with normal glucose tolerance. Binary logistic regression analysis showed that the homozygous variant of TCF7L2rs12255372 (T/T) is an independent risk factor for GDM (OR 7.7, 95% CI: 1.71-34.60), but not the homozygous variant of TCF7L2rs7903146 (T/T). CONCLUSIONS: TCF7L2rs12255372 variant (T/T) is associated with increased risk of GDM in Caucasian women.

Fetuin-A Characteristics during and after Pregnancy: Result from a Case Control Pilot Study.

Objective. Fetuin-A has been associated with gestational diabetes mellitus (GDM). We investigated fetuin-A levels during and after pregnancy in women with GDM. Fetuin-A measurements were performed in 10 women with GDM and 10 age and body mass index (BMI) matched healthy pregnant women. All women underwent an oral glucose tolerance test (OGTT) in and 3 months after gestation. Results. Fasting fetuin-A correlated with BMI in women with former GDM (r = 0.90, P < 0.0001) but showed no association with parameters of glucose tolerance in women with GDM or post-GDM. GDM featured significantly lower insulin sensitivity and higher insulin and C-peptide secretion profiles compared to NGT during pregnancy (P < 0.05). Fasting and postprandial fetuin-A did not differ between groups, neither during nor after pregnancy. Conclusion. Fetuin-A is not influenced by glucose tolerance during or after pregnancy or acute glucose elevations following glucose ingestion in young women, but closely relates to BMI early postpartum.

N-terminal-pro-brain natriuretic peptide is decreased in insulin dependent gestational diabetes mellitus: a prospective cohort trial.

BACKGROUND: N-terminal-pro-brain natriuretic peptide (NT-proBNP) is elevated in gestational hypertension and preeclampsia. This trial aimed to generate data for gestational diabetes mellitus patients, who are at risk to develop these complications. METHODS: We have measured NT-proBNP in 223 otherwise healthy women between gestational week 24 and 32 referred to the outpatient diabetes unit in a cross-sectional study. RESULTS: 88 control subjects, 45 patients with indication for medical nutrition therapy (MNT) alone and 90 patients who required insulin therapy were included. Groups of women were comparable regarding gestational week. Body mass index before pregnancy and at blood draw was significantly higher in subjects with insulin dependent gestational diabetes mellitus compared to MNT controlled gestational diabetes mellitus. NT-proBNP was significantly lower in patients with insulin dependent gestational diabetes mellitus (35 ± 25 pg/ml) compared to controls (53 ± 43 pg/ml, p = 0.012). CONCLUSIONS: NT-proBNP is within the reference range of normal subjects in women with gestational diabetes mellitus. Differences in body mass index, changes in glomerular filtration rate and haemodynamics may explain lower NT-proBNP concentrations in insulin dependent gestational diabetes mellitus. A false negative interpretation needs to be considered in these women.

Clinical characteristics, modalities and complications of diabetic patients with migration background at a Central European University Clinic.

The objective of the present study was to assess (i) the effects of immigration on the outcome of 200 consecutive singleton pregnancies in women with overt diabetes as well as (ii) gender-specific differences in cardiovascular risk factor profile and the achievement of therapeutic targets in type 2 diabetic subjects with migration background (n = 50). In pregnant subjects, baseline characteristics at admission, pregnancy outcome and the rate of obstetrical complications were similar in immigrant and non-immigrant women. Type 2 diabetes and also preconceptionally undiagnosed diabetes were significantly more frequent in women with migration background. Following delivery, immigrants presented with a worse metabolic profile, including higher triglyceride and nonHDL levels, than the indigenous population. Furthermore, within diabetic subjects with a migration background, non-pregnant women feature a more adverse cardiovascular risk factor profile than men. However, no gender-specific differences in the total adherence to clinical recommendations according to clinical recommendations have been found.

Risk factor profile and pregnancy outcome in women with type 1 and type 2 diabetes mellitus.

OBJECTIVE: To assess differences in congenital anomalies, infant mortality, and obstetrical complications as well as risk factors associated with an adverse pregnancy outcome in women with type 1 (T1DM) and type 2 diabetes mellitus (T2DM). METHODS: This observational study was performed at a university clinic and included a total of 200 singleton pregnancies between January 1995 and December 2006. Outcome measures comprise the prevalence of major congenital malformations, fetal losses, stillbirths, and neonatal deaths as well as the combined end point, adverse pregnancy outcome, and obstetrical complications. RESULTS: Despite changes in prevailing risk factors, the rate of congenital anomalies and embryonic as well as perinatal death was comparable in type 1 diabetic women over time as well as between women with T1DM and T2DM. Outcome measures and risk factor profile were similar in women with preconception and newly diagnosed T2DM. Glycemic control and increased body mass index (BMI) during the first trimester were the strongest predictors of an adverse pregnancy outcome. Hemoglobin A1c (HbA1c) was higher in T1DM than in T2DM but similar in women with T1DM over time. BMI was highest in women with T2DM, followed by T1DM women of the most recent time period. CONCLUSIONS: In addition to HbA1c, other risk factors, especially high BMI, strongly influence pregnancy outcome. The higher prevalence of these risk factors in T2DM might compensate for the better glycemic control, resulting in a pregnancy outcome comparable to that of T1DM. Pregnancy outcome in T1DM remained unchanged over time, possibly because of the missing amelioration of HbA1c levels and the increasing BMI.