Low circulating pentraxin 3 levels in pregnancy is associated with gestational diabetes and increased apoB/apoA ratio: a 5-year follow-up study

Lekva, Tove; Michelsen, Annika E.; Bollerslev, Jens; Norwitz, Errol R.; Aukrust, Pål; Henriksen, Tore; Ueland, Thor

doi:10.1186/s12933-016-0345-1

Cited by 22 publications

(24 citation statements)

References 44 publications

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“…We and others have shown that women with a history of GDM display an unfavorable lipid profile [27, 33, 34] with enhanced ratios such as TG/HDL-C as a marker of cardiometabolic risk [27]. While leptin and adiponectin, and their association with measures of adiposity and glucose metabolism are well established in GDM, their associations with surrogate markers of CV risk in these women, or during normal pregnancy, are less documented.…”

Section: Discussionmentioning

confidence: 99%

Leptin and adiponectin as predictors of cardiovascular risk after gestational diabetes mellitus

Lekva

Michelsen

Aukrust

et al. 2017

Cardiovasc Diabetol

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BackgroundGestational 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.MethodsThis 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.ResultsWe found the L/A ratio higher in GDM women both during pregnancy and follow-up compared to non-GDM 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.ConclusionsTaken 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s12933-016-0492-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Leptin and adiponectin as predictors of cardiovascular risk after gestational diabetes mellitus

Lekva

Michelsen

Aukrust

et al. 2017

Cardiovasc Diabetol

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“…The distribution of PAPP-A was investigated in pregnant women and found that it varies by ethnicity, gestational age, maternal weight and smoking status [31–35]. The clinical investigations of the complex relationship among PAPP-A levels during pregnancy, gestational diabetes (GDM) and cardiovascular disease risk are evolving [36–39]. Low levels of PAPP-A during the first trimester are associated with fetal Down’s syndrome [40] and other adverse events [37, 41–43].…”

Section: Discussionmentioning

confidence: 99%

Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus

Neradilek

et al. 2017

Cardiovasc Diabetol

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BackgroundThe risk prediction of pregnancy-associated plasma protein-A (PAPP-A) for future cardiovascular (CV) events post acute coronary syndrome (ACS) in patients with type-2 diabetes mellitus (T2DM) was investigated in comparison to other risk factors.MethodsPAPP-A was measured at hospital admission in 320 consecutive ACS patients (136 with T2DM and 184 without). All patients were followed for 2 years for occurrence of CV death, non-fatal MI or stroke. Effect of PAPP-A on the CV event risk was estimated using Cox regression models. Receiver operating characteristics (ROC) curves were generated to demonstrate the sensitivity and specificity of PAPP-A in predicting CV events.ResultsACS patients with T2DM had higher PAPP-A (19.29 ± 16.36 vs. 13.29 ± 13.90 ng/ml, p < 0.001) and higher rate of CV events 2 years post ACS (27.2 vs. 13.6%, p = 0.002) than those without. Higher levels of PAPP-A were significantly associated with increased risk of CV events during 2-year follow-up [HR = 2.97 for 1 SD increase in log10(PAPP-A), 95% CI 2.11–4.18, p < 0.001] in T2DM and (HR = 3.16, 95% CI 2.27–4.39, p < 0.001) in non-T2DM. Among patients with T2DM, PAPP-A showed a larger area under the curve (AUC 0.79) that was significantly more predictive than hsCRP (AUC 0.64), eGFR (AUC 0.66) and LVEF < 50% (AUC 0.52); predictive ability did not improve significantly by including those factors into the model.ConclusionsPatients with T2DM had higher levels of PAPP-A and increased risk of CV events. Elevated PAPP-A compared to other risk factors was a stronger predictor for future CV events 2 years post ACS in patients with T2DM. Trial registration ISRCTN10805074. Registered on 20 January 2017, retrospectively registered.

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“…All samples were stored at −80°C and thawed less than three times. Adipokines (adipsin [DY1824], adiponectin [DY1065], chemerin [DY2324], leptin [DY398], resistin [DY1359], clusterin [DY5874]) and monocyte/macrophage markers (sCD163 [DY1607], sCD14 [DY383]) were measured in duplicate using commercially available antibodies (R&D Systems, Minneapolis, Minnesota) while CRP (DY1707) was measured as previously reported, also with commercially available antibodies (R&D Systems, Minneapolis, Minnesota), and IL‐1Ra (900 K574) was measured with antibodies from PeproTech (Rocky Hill, New Jersey), in a 384 format using the combination of a SELMA (Jena, Germany) pipetting robot and a BioTek (Winooski, Vermont) dispenser/washer (EL406). Absorption was read at 450 nm with wavelength correction set to 540 nm using an ELISA plate reader (Synergy H1 Hybrid, Biotek, Vinooski, Vermont).…”

Section: Methodsmentioning

confidence: 99%

Adipokines and macrophage markers during pregnancy—Possible role for sCD163 in prediction and progression of gestational diabetes mellitus

Ueland

Michelsen

Aukrust

et al. 2019

Diabetes Metabolism Res

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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 long‐term follow‐up. Materials and methods Population‐based prospective cohort study in 273 pregnant women with markers measured four times during pregnancy and at 5‐year follow‐up. Results sCD163 was higher (25% at 14‐16 weeks, P < 0.001) and adiponectin lower (−17% at 14‐16 weeks, P < 0.01) early in pregnancy and at 5‐year follow‐up in GDM women, independent of BMI, and other GDM risk factors. Leptin, adiponectin, and chemerin were robustly associated with glucose metabolism throughout pregnancy while sCD163 was inversely associated with β‐cell function early in pregnancy in women with increased BMI. Finally, the markers at 14 to 16 weeks displayed modest discriminatory properties with regard to prediction of GDM (AUC < 0.7). Using a combination of fasting glucose and sCD163, 53% of GDM could be identified when 25% of the population scored positive suggesting some merit in a multimarker approach. 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.

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Low circulating pentraxin 3 levels in pregnancy is associated with gestational diabetes and increased apoB/apoA ratio: a 5-year follow-up study

Cited by 22 publications

References 44 publications

Leptin and adiponectin as predictors of cardiovascular risk after gestational diabetes mellitus

Leptin and adiponectin as predictors of cardiovascular risk after gestational diabetes mellitus

Pregnancy-associated plasma protein-A is a stronger predictor for adverse cardiovascular outcomes after acute coronary syndrome in type-2 diabetes mellitus

Adipokines and macrophage markers during pregnancy—Possible role for sCD163 in prediction and progression of gestational diabetes mellitus

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