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Laaksonen, J.* ; Taipale, T.* ; Seppälä, I.* ; Raitoharju, E.* ; Mononen, N.* ; Lyytikäinen, L.-P.* ; Waldenberger, M. ; Illig, T. ; Hutri-Kähönen, N.* ; Rönnemaa, T.* ; Juonala, M.* ; Viikari, J.* ; Kähönen, M.* ; Raitakari, O.* ; Lehtimäki, T.*

Blood pathway analyses reveal differences between prediabetic subjects with or without dyslipidaemia. The Cardiovascular Risk in Young Finns Study.

Diabetes Metab. Res. Rev. 33:e2914 (2017)
Open Access Green as soon as Postprint is submitted to ZB.
Background: Prediabetes often occurs together with dyslipidaemia, which is paradoxically treated with statins predisposing to type 2 diabetes mellitus. We examined peripheral blood pathway profiles in prediabetic subjects with (PR D ) and without dyslipidaemia (PR 0 ) and compared these to nonprediabetic controls without dyslipidaemia (C 0 ). Methods: The participants were from the Cardiovascular Risk in Young Finns Study, including 1240 subjects aged 34 to 49 years. Genome-wide expression data of peripheral blood and gene set enrichment analysis were used to investigate the differentially expressed genes and enriched pathways between different subtypes of prediabetes. Results: Pathways for cholesterol synthesis, interleukin-12-mediated signalling events, and downstream signalling in naïve CD8+ T-cells were upregulated in the PR 0 group in comparison with controls (C 0 ). The upregulation of these pathways was independent of waist circumference, blood pressure, smoking status, and insulin. Adjustment for CRP left the CD8+ T-cell signalling and interleukin-12-mediated signalling event pathway upregulated. The cholesterol synthesis pathway was also upregulated when all prediabetic subjects (PR 0 and PR D ) were compared with the nonprediabetic control group. No pathways were upregulated or downregulated when the PR D group was compared with the C 0 group. Five genes in the PR 0 group and 1 in the PR D group were significantly differentially expressed in comparison with the C 0 group. Conclusions: Blood cell gene expression profiles differ significantly between prediabetic subjects with and without dyslipidaemia. Whether this classification may be used in detection of prediabetic individuals at a high risk of cardiovascular complications remains to be examined.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Dyslipidaemia ; Gene Expression ; Gene Set Enrichment Analysis ; Prediabetes; Coronary-heart-disease; Fatty Liver-disease; Insulin-resistance Atherosclerosis; Macrophage Scavenger Receptors; Impaired Glucose-tolerance; Diabetes-mellitus; Fasting Glucose; Gene-expression; Cholesterol-metabolism; Lipoprotein
ISSN (print) / ISBN 1520-7552
e-ISSN 1520-7560
Quellenangaben Volume: 33, Issue: 7, Pages: , Article Number: e2914 Supplement: ,
Publisher Wiley
Publishing Place Hoboken
Reviewing status Peer reviewed