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

Diabetes Metab Res Rev. 2017 Oct;33(7). doi: 10.1002/dmrr.2914. Epub 2017 Aug 2.

Abstract

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 (PRD ) and without dyslipidaemia (PR0 ) and compared these to nonprediabetic controls without dyslipidaemia (C0 ).

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 PR0 group in comparison with controls (C0 ). 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 (PR0 and PRD ) were compared with the nonprediabetic control group. No pathways were upregulated or downregulated when the PRD group was compared with the C0 group. Five genes in the PR0 group and 1 in the PRD group were significantly differentially expressed in comparison with the C0 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.

Keywords: dyslipidaemia; gene expression; gene set enrichment analysis; prediabetes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Blood Glucose
  • Cardiovascular Diseases / etiology*
  • Cardiovascular Diseases / genetics
  • Cholesterol / biosynthesis*
  • Dyslipidemias / blood
  • Dyslipidemias / complications
  • Dyslipidemias / genetics*
  • Female
  • Finland
  • Gene Expression Profiling
  • Gene Expression*
  • Humans
  • Insulin Resistance
  • Male
  • Middle Aged
  • Prediabetic State / blood
  • Prediabetic State / complications
  • Prediabetic State / genetics*
  • Signal Transduction / genetics*
  • Up-Regulation
  • Waist Circumference

Substances

  • Blood Glucose
  • Cholesterol