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- Tschiderer, Lena, et al.
(författare)
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Association of Intima-Media Thickness Measured at the Common Carotid Artery With Incident Carotid Plaque : Individual Participant Data Meta-Analysis of 20 Prospective Studies
- 2023
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 12:12
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Tidskriftsartikel (refereegranskat)abstract
- Background: The association between common carotid artery intima-media thickness (CCA-IMT) and incident carotid plaque has not been characterized fully. We therefore aimed to precisely quantify the relationship between CCA-IMT and carotid plaque development.Methods and Results: We undertook an individual participant data meta-analysis of 20 prospective studies from the Proof-ATHERO (Prospective Studies of Atherosclerosis) consortium that recorded baseline CCA-IMT and incident carotid plaque involving 21 494 individuals without a history of cardiovascular disease and without preexisting carotid plaque at baseline. Mean baseline age was 56 years (SD, 9 years), 55% were women, and mean baseline CCA-IMT was 0.71 mm (SD, 0.17 mm). Over a median follow-up of 5.9 years (5th-95th percentile, 1.9-19.0 years), 8278 individuals developed first-ever carotid plaque. We combined study-specific odds ratios (ORs) for incident carotid plaque using random-effects meta-analysis. Baseline CCA-IMT was approximately log-linearly associated with the odds of developing carotid plaque. The age-, sex-, and trial arm-adjusted OR for carotid plaque per SD higher baseline CCA-IMT was 1.40 (95% CI, 1.31-1.50; I-2=63.9%). The corresponding OR that was further adjusted for ethnicity, smoking, diabetes, body mass index, systolic blood pressure, low- and high-density lipoprotein cholesterol, and lipid-lowering and antihypertensive medication was 1.34 (95% CI, 1.24-1.45; I-2=59.4%; 14 studies; 16 297 participants; 6381 incident plaques). We observed no significant effect modification across clinically relevant subgroups. Sensitivity analysis restricted to studies defining plaque as focal thickening yielded a comparable OR (1.38 [95% CI, 1.29-1.47]; I-2=57.1%; 14 studies; 17 352 participants; 6991 incident plaques).Conclusions: Our large-scale individual participant data meta-analysis demonstrated that CCA-IMT is associated with the long-term risk of developing first-ever carotid plaque, independent of traditional cardiovascular risk factors.
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| 2. |
- Slieker, Roderick C, et al.
(författare)
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Distinct Molecular Signatures of Clinical Clusters in People with Type 2 Diabetes : an IMIRHAPSODY Study
- 2021
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Ingår i: Diabetes. - : American Diabetes Association. - 1939-327X .- 0012-1797. ; 70:11, s. 2683-2693
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Tidskriftsartikel (refereegranskat)abstract
- Type 2 diabetes is a multifactorial disease with multiple underlying aetiologies. To address this heterogeneity a previous study clustered people with diabetes into five diabetes subtypes. The aim of the current study is to investigate the aetiology of these clusters by comparing their molecular signatures. In three independent cohorts, in total 15,940 individuals were clustered based on five clinical characteristics. In a subset, genetic- (N=12828), metabolomic- (N=2945), lipidomic- (N=2593) and proteomic (N=1170) data were obtained in plasma. In each datatype each cluster was compared with the other four clusters as the reference. The insulin resistant cluster showed the most distinct molecular signature, with higher BCAAs, DAG and TAG levels and aberrant protein levels in plasma enriched for proteins in the intracellular PI3K/Akt pathway. The obese cluster showed higher cytokines. A subset of the mild diabetes cluster with high HDL showed the most beneficial molecular profile with opposite effects to those seen in the insulin resistant cluster. This study showed that clustering people with type 2 diabetes can identify underlying molecular mechanisms related to pancreatic islets, liver, and adipose tissue metabolism. This provides novel biological insights into the diverse aetiological processes that would not be evident when type 2 diabetes is viewed as a homogeneous disease.
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| 3. |
- Slieker, Roderick C, et al.
(författare)
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Identification of biomarkers for glycaemic deterioration in type 2 diabetes
- 2023
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Ingår i: Nature Communications. - 2041-1723. ; 14, s. 1-18
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Tidskriftsartikel (refereegranskat)abstract
- We identify biomarkers for disease progression in three type 2 diabetes cohorts encompassing 2,973 individuals across three molecular classes, metabolites, lipids and proteins. Homocitrulline, isoleucine and 2-aminoadipic acid, eight triacylglycerol species, and lowered sphingomyelin 42:2;2 levels are predictive of faster progression towards insulin requirement. Of ~1,300 proteins examined in two cohorts, levels of GDF15/MIC-1, IL-18Ra, CRELD1, NogoR, FAS, and ENPP7 are associated with faster progression, whilst SMAC/DIABLO, SPOCK1 and HEMK2 predict lower progression rates. In an external replication, proteins and lipids are associated with diabetes incidence and prevalence. NogoR/RTN4R injection improved glucose tolerance in high fat-fed male mice but impaired it in male db/db mice. High NogoR levels led to islet cell apoptosis, and IL-18R antagonised inflammatory IL-18 signalling towards nuclear factor kappa-B in vitro. This comprehensive, multi-disciplinary approach thus identifies biomarkers with potential prognostic utility, provides evidence for possible disease mechanisms, and identifies potential therapeutic avenues to slow diabetes progression.
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