89 research outputs found
Leptin and adiponectin as predictors of cardiovascular risk after gestational diabetes mellitus
Source at https://doi.org/10.1186/s12933-016-0492-4.Background: Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life, but the mechanism remains unclear. Adipokine imbalance in the presence of metabolic dysfunction may be a key event in promoting CVD. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma adiponectin, leptin and the leptin/adiponectin (L/A) ratio in pregnancy and at 5 years after the index pregnancy.
Methods: This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy X-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting adiponectin and leptin levels were measured four times during pregnancy and at follow-up.
Results: We found the L/A ratio higher in GDM women during both pregnancy and follow-up compared to nonGDM women. A high L/A ratio during pregnancy was associated with CV risk based on lipid ratios at follow-up, especially the TG/HDL-C ratio. Further, interaction analysis indicated that an increase in the L/A ratio of 1 unit was associated with a higher CV risk in GDM compared to normal pregnancy. Finally, low adiponectin levels independently predicted increased lipid ratios at follow-up.
Conclusions: Taken together, our findings suggest that high L/A ratio in pregnancy and in particularly in those with GDM are associated with an unfavorable CVD risk profile during follow-up. Future studies should investigate if a dysregulated leptin and adiponectin profile during pregnancy is associated with atherosclerotic disease during long-term follow-up
Serum amyloid A1 and pregnancy zone protein in pregnancy complications and correlation with markers of placental dysfunction
BACKGROUND: Hypertensive disorders of pregnancy (preeclampsia,
gestational hypertension, and chronic hypertension), diabetes mellitus,
and placental dysfunction confer an increased risk of long-term maternal
cardiovascular disease. Preeclampsia is also associated with acute atherosis that involves lesions of uteroplacental spiral arteries, resembling early
stages of atherosclerosis. Serum amyloid A1 is involved in hypercoagulability and atherosclerosis and may aggregate into amyloidâaggregations
of misfolded proteins. Pregnancy zone protein may inhibit amyloid aggregation. Amyloid is involved in Alzheimer's disease and cardiovascular disease; it has been identified in preeclampsia, but its role in preeclampsia
pathophysiology is unclear.
OBJECTIVE: We hypothesized that serum amyloid A1 would be
increased and pregnancy zone protein decreased in hypertensive disorders
of pregnancy and diabetic pregnancies and that serum amyloid A1 and
pregnancy zone protein would correlate with placental dysfunction
markers (fetal growth restriction and dysregulated angiogenic biomarkers)
and acute atherosis.
STUDY DESIGN: Serum amyloid A1 is measurable in both the serum
and plasma. In our study, plasma from 549 pregnancies (normotensive,
euglycemic controls: 258; early-onset preeclampsia: 71; late-onset preeclampsia: 98; gestational hypertension: 30; chronic hypertension: 9; diabetes mellitus: 83) was assayed for serum amyloid A1 and pregnancy
zone protein. The serum levels of angiogenic biomarkers soluble fms-like
tyrosine kinase-1 and placental growth factor were available for 547
pregnancies, and the results of acute atherosis evaluation were available
for 313 pregnancies. The clinical characteristics and circulating biomarkers were compared between the pregnancy groups using the MannWhitney U, chi-squared, or Fisher exact test as appropriate. Spearmanâs
rho was calculated for assessing correlations.
RESULTS: In early-onset preeclampsia, serum amyloid A1 was
increased compared with controls (17.1 vs 5.1 mg/mL, P<.001), whereas
pregnancy zone protein was decreased (590 vs 892 mg/mL, P=.002).
Pregnancy zone protein was also decreased in diabetes compared with
controls (683 vs 892 mg/mL, P=.01). Serum amyloid A1 was associated
with placental dysfunction (fetal growth restriction, elevated soluble fmslike tyrosine kinase-1 to placental growth factor ratio). Pregnancy zone
protein correlated negatively with soluble fms-like tyrosine kinase-1 to placental growth factor ratio in all study groups. Acute atherosis was not
associated with serum amyloid A1 or pregnancy zone protein.
CONCLUSION: Proteins involved in atherosclerosis, hypercoagulability, and protein misfolding are dysregulated in early-onset preeclampsia
and placental dysfunction, which links them and potentially contributes to
future maternal cardiovascular disease
Genetic determinants of glucose levels in pregnancy: genetic risk scores analysis and GWAS in the Norwegian STORK cohort
Objective: Hyperglycaemia during pregnancy increases the risk of adverse health outcomes in mother and child, but the genetic aetiology is scarcely studied. Our aims were to (1) assess the overlapping genetic aetiology between the pregnant and non-pregnant population and (2) assess the importance of genome-wide polygenic contributions to glucose traits during pregnancy, by exploring whether genetic risk scores (GRSs) for fasting glucose (FG), 2-h glucose (2hG), type 2 diabetes (T2D) and BMI in non-pregnant individuals were associated with glucose measures in pregnant women. Methods: We genotyped 529 Norwegian pregnant women and constructed GRS from known genome-wide significant variants and SNPs weakly associated (p>5Ă10â) with FG, 2hG, BMI and T2D from external genome-wide association studies (GWAS) and examined the association between these scores and glucose measures at gestational weeks 14-16 and 30-32. We also performed GWAS of FG, 2hG and shape information from the glucose curve during an oral glucose tolerance test (OGTT). Results: GRS explained similar variance during pregnancy as in the non-pregnant population (~5%). GRS and GRS explained up to 1.3% of the variation in the glucose traits in pregnancy. If we included variants more weakly associated with these traits, GRS and GRS explained up to 2.4% of the variation in the glucose traits in pregnancy, highlighting the importance of polygenic contributions. Conclusions: Our results suggest overlap in the genetic aetiology of FG in pregnant and non-pregnant individuals. This was less apparent with 2hG, suggesting potential differences in postprandial glucose metabolism inside and outside of pregnancy
Increased circulating IL-18 levels in severe mental disorders indicate systemic inflammasome activation
Background
Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental illnesses (SMI) that are part of a psychosis continuum, and dysregulated innate immune responses have been suggested to be involved in their pathophysiology. However, disease-specific immune mechanisms in SMI are not known yet. Recently, dyslipidemia has been linked to systemic inflammasome activation, and elevated atherogenic lipid ratios have been shown to correlate with circulating levels of inflammatory biomarkers in SMI. It is, however, not yet known if increased systemic cholesterol load leads to inflammasome activation in these patients.
Methods
We tested the hypothesis that patients with SCZ and BD display higher circulating levels compared to healthy individuals of key members of the IL-18 system using a large patient cohort (nâŻ=âŻ1632; including 737 SCZ and 895 BD), and healthy controls (CTRL; nâŻ=âŻ1070). In addition, we assessed associations with coronary artery disease risk factors in SMI, focusing on relevant inflammasome-related, neuroendocrine, and lipid markers.
Results
We report higher baseline levels of circulating IL-18 system components (IL-18, IL-18BPA, IL-18R1), and increased expression of inflammasome-related genes (NLRP3 and NLRC4) in the blood of patients relative to CTRL. We demonstrate a cholesterol dyslipidemia pattern in psychotic disorders, and report correlations between levels of blood cholesterol types and the expression of inflammasome system elements in SMI.
Conclusions
Based on these results, we suggest a role for inflammasome activation/dysregulation in SMI. Our findings further the understanding of possible underlying inflammatory mechanisms and may expose important therapeutic targets in SMI.publishedVersio
Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterations
Background: Although coronavirus disease 2019 (COVID-19) is primarily a respiratory infection, mounting evidence suggests that the gastrointestinal (GI) tract is involved in the disease, with gut barrier dysfunction and gut microbiota alterations being related to disease severity. Whether these alterations persist and are related to long-term respiratory dysfunction remains unknown. Methods: Plasma was collected during hospital admission and after three months from the NOR-Solidarity trial (n = 181) and analysed for markers of gut barrier dysfunction and inflammation. At the three-month follow-up, pulmonary function was assessed by measuring the diffusing capacity of the lungs for carbon monoxide (DLCO ). Rectal swabs for gut microbiota analyses were collected (n = 97) and analysed by sequencing the 16S rRNA gene. Results: Gut microbiota diversity was reduced in COVID-19 patients with respiratory dysfunction, defined as DLCO below the lower limit of normal three months after hospitalisation. These patients also had an altered global gut microbiota composition, with reduced relative abundance of 20 bacterial taxa and increased abundance of five taxa, including Veillonella, potentially linked to fibrosis. During hospitalisation, increased plasma levels of lipopolysaccharide-binding protein (LBP) were strongly associated with respiratory failure, defined as pO2 /fiO2 -(P/F ratio)Respiratory dysfunction three months after severe COVID-19 is associated with gut microbiota alterationsacceptedVersio
Low circulating pentraxin 3 levels in pregnancy is associated with gestational diabetes and increased apoB/apoA ratio: a 5-year follow-up study
Multi-ancestry genome-wide association study of gestational diabetes mellitus highlights genetic links with type 2 diabetes
Gestational diabetes mellitus (GDM) is associated with increased risk of pregnancy complications and adverse perinatal outcomes. GDM often reoccurs and is associated with increased risk of subsequent diagnosis of type 2 diabetes (T2D). To improve our understanding of the aetiological factors and molecular processes driving the occurrence of GDM, including the extent to which these overlap with T2D pathophysiology, the GENetics of Diabetes In Pregnancy Consortium assembled genome-wide association studies of diverse ancestry in a total of 5485 women with GDM and 347 856 without GDM. Through multi-ancestry meta-analysis, we identified five loci with genome-wide significant association (P < 5 x 10(-8)) with GDM, mapping to/near MTNR1B (P = 4.3 x 10(-54)), TCF7L2 (P = 4.0 x 10(-16)), CDKAL1 (P = 1.6 x 10(-4)), CDKN2A-CDKN2B (P = 4.1 x 10(-9)) and HKDC1 (P = 2.9 x 10(-8)). Multiple lines of evidence pointed to the shared pathophysiology of GDM and T2D: (i) four of the five GDM loci (not HKDC1) have been previously reported at genome-wide significance for T2D; (ii) significant enrichment for associations with GDM at previously reported T2D loci; (iii) strong genetic correlation between GDM and T2D and (iv) enrichment of GDM associations mapping to genomic annotations in diabetes-relevant tissues and transcription factor binding sites. Mendelian randomization analyses demonstrated significant causal association (5% false discovery rate) of higher body mass index on increased GDM risk. Our results provide support for the hypothesis that GDM and T2D are part of the same underlying pathology but that, as exemplified by the HKDC1 locus, there are genetic determinants of GDM that are specific to glucose regulation in pregnancy.Peer reviewe
Low circulating pentraxin 3 levels in pregnancy is associated with gestational diabetes and increased apoB/apoA ratio: a 5-year follow-up study
Background
Gestational diabetes mellitus (GDM) is a significant risk factor for cardiovascular disease (CVD) in later life. Pentraxin 3 (PTX3) is an essential component of innate immunity and independently associated with the risk of developing vascular events. The aim of the study was to examine the relationships between GDM, cardiovascular risk, and plasma PTX3 in pregnancy and at 5Â years after the index pregnancy.
Methods
This population-based prospective cohort included 300 women who had an oral glucose tolerance test (OGTT) during pregnancy. Five years later, the OGTT was repeated along with dual-energy x-ray absorptiometry, lipid analysis, and pulse wave velocity analysis. Fasting PTX3 levels were measured four times during pregnancy and at follow-up.
Results
PTX3 levels were lower early in pregnancy and at 5Â years follow-up in women who developed GDM. PTX3 levels throughout pregnancy were associated with body mass index. Low PTX3 levels in early pregnancy were predictive of an increased apoB/apoA ratio at 5-year follow-up. PTX3 at 5-year follow-up was inversely correlated with multiple metabolic risk factors for CVD, including body composition, arterial stiffness, dyslipidemia and previous GDM.
Conclusions
Our results show that low plasma concentration of PTX3 in early pregnancy is associated with subsequent development of GDM and with an enhanced risk for CVD as estimated by an elevated apoB/apoA ratio at 5Â years postpartum
Adipokines and macrophage markers during pregnancy?Possible role for sCD163 in prediction and progression of gestational diabetes mellitus
Aims - The risk of gestational diabetes mellitus (GDM) is increased in overweight and obese women potentially involving secreted mediators from adipose tissue. Our main aim was to evaluate if circulating adipokines and monocyte/macrophage markers were dysregulated in GDM and the influence body mass and indices of glucose metabolism had on this association. We further explored if early detection of these markers improved prediction of GDM and if they remained modified during longâterm followâup.
Materials and methods - Populationâbased prospective cohort study in 273 pregnant women with markers measured four times during pregnancy and at 5âyear followâup.
Results - sCD163 was higher (25% at 14â16 weeks, P P
Conclusions - sCD163 and adiponectin were dysregulated in GDM, independent of body mass. None of the adipokines or monocyte/macrophage activation markers displayed clinically useful properties alone for early detection of GDM. Activation of monocytes/macrophages may be an important event in the early development of GDM
Low CETP activity and unique composition of large VLDL and small HDL in women giving birth to small-for-gestational age infants
Abstract Cholesteryl ester transfer protein (CETP) regulates high density lipoproteins (HDL)-cholesterol (C) and HDL-C is essential for fetal development. We hypothesized that women giving birth to large-for-gestational-age (LGA) and small-for-gestational age (SGA) infants differed in longitudinal changes in lipoproteins, CETP activity and HDL-C and that placentas from women with higher or lower circulating HDL-C displayed differential expression of mRNAs involved in cholesterol/nutrient transport, insulin signaling, inflammation/ extracellular matrix (ECM) remodeling. Circulating lipids and CETP activity was measured during pregnancy, NMR lipidomics in late pregnancy, and associations with LGA and SGA infants investigated. RNA sequencing was performed in 28 placentas according to higher and lower maternal HDL-C levels. Lipidomics revealed high triglycerides in large VLDL and lipids/cholesterol/cholesteryl esters in small HDL in women giving birth to SGA infants. Placentas from women with higher HDL-C had decreased levels of CETP expression which was associated with mRNAs involved in cholesterol/nutrient transport, insulin signaling and inflammation/ECM remodeling. Both placental and circulating CETP levels were associated with growth of the fetus. Low circulating CETP activity at 36â38Â weeks was associated with giving birth to SGA infants. Our findings suggest a link between increased maternal HDL-C levels, low CETP levels both in circulation and placenta, and SGA infants
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