BackgroundHistory of gestational diabetes mellitus (GDM) identifies a very young population of females predisposed for type 2 diabetes and cardiovascular disease. Endothelial dysfunction might represent a shared precursor of both disorders. Hence, this study aimed to characterize endothelial biomarkers in relation to impaired insulin sensitivity and progression to overt diabetes early after index pregnancy.Methods108 women with previous GDM and 40 controls were included three to six months after delivery and underwent specific metabolic assessments including a frequently sampled intravenous glucose tolerance test and an oral glucose tolerance test. Diabetes progression was assessed in females with pGDM over 10 years of follow-up. Circulating sICAM-1 (intracellular-adhesion-molecule-1), sVCAM-1 (vascular-cell-adhesion-molecule-1) and sE-selectin, representing biomarkers of endothelial dysfunction were assessed at baseline and annually over five years.ResultsEndothelial biomarkers were significantly associated with insulin sensitivity (sICAM-1: r = -0.23, p = 0.009; sVCAM-1: r = -0.22, p = 0.011; sE-selectin: r = -0.21, p = 0.018) as well as with GDM status and parameters of subtle inflammation. Analysis of long-term trajectories revealed constantly elevated sICAM-1 (p = 0.033) and sE-selectin (p = 0.007) in 25 subjects with diabetes progression. Accordingly, sE-selectin levels at the early post partum visit predicted a later development of the disease (HR =1.02 95%CI 1.01 to 1.04, p = 0.013), however, this was attenuated after adjustment for BMI.ConclusionsElevated circulating markers of endothelial dysfunction in young females with GDM history might reflect an early stage on the pathway to the manifestation of future cardiometabolic disorders. Timely identification of women at high risk and optimization of follow-up management might provide an opportunity to prevent disease progression.

Compared to the 2-h oral glucose tolerance test (OGTT), the assessment of HbA1c was proposed as a less time-consuming alternative to detect pathologies in carbohydrate metabolism. This report aims to assess the predictive accuracy of HbA1c to detect alterations in glucose disposition early after gestational diabetes mellitus (GDM) pregnancy. A detailed metabolic characterization was performed in 77 women with previous GDM (pGDM) and 41 controls 3-6 month after delivery: 3-h OGTT, frequently sampled intravenous glucose tolerance test. Follow-up examinations of pGDMs were performed up to 10 years. HbA1c (venous samples, HPLC) was assessed at baseline as well as during the follow-up period (475 patient contacts). Moderate associations were observed between HbA1c and measurements of plasma glucose during the OGTT at the baseline examination: The strongest correlation was found for FPG (r = 0.40, p < 0.001), decreasing after ingestion. No associations were detected between HbA1c and OGTT dynamics of insulin or C-peptide. Moreover, baseline HbA1c showed only modest correlation with insulin sensitivity (r = -0.25, p = 0.010) and disposition index (r = -0.26, p = 0.007). A linear model including fasting as well as post-load glucose levels was not improved by HbA1c. However, pGDM females with overt diabetes manifestation during the follow-up period showed more pronounced increasing HbA1c in contrast to females remaining normal glucose tolerant or developing prediabetes. It is suggested that the performance of HbA1c assessed early after delivery is inferior to the OGTT for the detection of early alterations in glucose metabolism. However, an increase in HbA1c levels could be used as an indicator of risk for diabetes manifestation.

BackgroundIn patients with refractory heart failure (HF) peritoneal dialysis (PD) is associated with improved functional status and decrease in hospitalization. However, previous studies did not focus on right ventricular dysfunction as an important pathophysiologic component of cardiorenal syndrome.MethodsIn a prospective cohort study PD was started in 40 patients with refractory right HF (with/without left HF). Refractoriness to conservative therapy was defined as persistent right heart congestion/ascites with intensified diuretic treatment and/or ≥2 hospitalizations within 6 months because of cardiac decompensation despite optimal medical treatment, and/or acute renal failure during intensified conservative treatment of cardiac decompensations.ResultsPatient survival was 55.0% at 1 year, 35.0% at 2 years and 27.5% at 3 years. The number of hospitalization days declined after initiation of PD for both cardiac [13 (IQR 1–53) days before vs. 1 (IQR 0–12) days after start of PD, p<0.001] and unplanned reasons [12 (IQR 3–44) days before vs. 1 (IQR 0–33) days after start of PD, p = 0.007]. Using a combined endpoint including survival time of ≥1 year and either improvement in quality of life or decline in hospitalizations we found that patients with extended ascites, higher systolic pulmonary artery pressure, more marked impairment of right ventricular function and tricuspid valve insufficiency, higher residual renal function as well as those who could perform PD without assistance have benefited most from this therapy.ConclusionsPatients with more pronounced backward failure, less marked residual renal functional impairment and those not depending on assistance for therapy are likely to profit most from PD.

Early reexamination of carbohydrate metabolism via an oral glucose tolerance test (OGTT) is recommended after pregnancy with gestational diabetes (GDM). In this report, we aimed to assess the dominant patterns of dynamic OGTT measurements and subsequently explain them by meanings of the underlying pathophysiological processes. Principal components analysis (PCA), a statistical procedure that aims to reduce the dimensionality of multiple interrelated measures to a set of linearly uncorrelated variables (the principal components) was performed on OGTT data of glucose, insulin and C-peptide in addition to age and body mass index (BMI) of 151 women (n = 110 females after GDM and n = 41 controls) at 3-6 mo after delivery. These components were explained by frequently sampled intravenous glucose tolerance test (FSIGT) parameters. Moreover, their relation with the later development of overt diabetes was studied. Three principal components (PC) were identified, which explained 71.5% of the variation of the original 17 variables. PC1 (explained 47.1%) was closely related to postprandial OGTT levels and FSIGT-derived insulin sensitivity (r = 0.68), indicating that it mirrors insulin sensitivity in the skeletal muscle. PC2 (explained 17.3%) and PC3 (explained 7.1%) were shown to be associated with β-cell failure and fasting (i.e., hepatic) insulin resistance, respectively. All three components were related with diabetes progression (occurred in n = 25 females after GDM) and showed significant changes in long-term trajectories. A high amount of the postpartum OGTT data is explained by principal components, representing pathophysiological mechanisms on the pathway of impaired carbohydrate metabolism. Our results improve our understanding of the underlying biological processes to provide an accurate postgestational risk stratification.

Objective: In the long term, diabetes mellitus is potentially associated with the occurrence of microvascular damage. This study sought to assess whether a history of prior gestational diabetes mellitus is associated with long-term effects on the women's microcirculation. Methods: Within the scope of a long-term follow-up of the 'Viennese Post-Gestational Diabetes Project', women with prior gestational diabetes mellitus as well as women with previous pregnancy but with no history of gestational diabetes mellitus (controls) were enrolled in this cross-sectional study. Microvascular function was assessed by post-occlusive reactive hyperaemia using laser Doppler fluxmetry. Baseline perfusion, biological zero, peak perfusion, time to peak and recovery time were recorded and compared between both groups. Results: Microvascular function was assessed in 55 women with prior gestational diabetes mellitus (46.1 ± 4.6 years) and 32 women with previous pregnancy but without prior gestational diabetes mellitus (42.9 ± 5.3 years). The mean period of time between delivery and the assessment of microvascular function was 16.2 ± 5.2 years in women with prior gestational diabetes mellitus group and 14.2 ± 4.8 years in controls. Regarding microvascular function, baseline perfusion, biological zero, peak perfusion, time to peak and recovery time did not differ between women with prior gestational diabetes mellitus and controls (all p > 0.05). Conclusion:In the long term, microvascular function appears not to be impaired in women with prior gestational diabetes mellitus.