Hsa_circ_0054633 in peripheral blood can be used as a diagnostic biomarker of pre-diabetes and type 2 diabetes mellitus

Acta Diabetol. 2017 Mar;54(3):237-245. doi: 10.1007/s00592-016-0943-0. Epub 2016 Nov 23.


Aims: The purpose of the current study was to investigate the characteristic expression of circular RNAs (circRNAs) in the peripheral blood of type 2 diabetes mellitus (T2DM) patients and their potential as diagnostic biomarkers for pre-diabetes and T2DM.

Methods: CircRNAs in the peripheral blood from six healthy individuals and six T2DM patients were collected for microarray analysis, and an independent cohort study consisting of 20 normal cases, 20 pre-diabetes patients and 20 T2DM patients was conducted to verify the five chosen circRNAs. We then tested hsa_circ_0054633 in a third cohort (control group, n = 60; pre-diabetes group, n = 63; and T2DM group, n = 64) by quantitative real-time polymerase chain reaction (Q-PCR).

Results: In total, 489 circRNAs were discovered to be differentially expressed between the two groups, and of these, 78 were upregulated and 411 were downregulated in the T2DM group. Five circRNAs were then selected as candidate biomarkers and further verified in a second cohort. Hsa_circ_0054633 was found to have the largest area under the curve (AUC). The diagnostic capacity of hsa_circ_0054633 was tested in a third cohort. After introducing the risk factors of T2DM, the hsa_circ_0054633 AUCs for the diagnosis of pre-diabetes and T2DM slightly increased from 0.751 (95% confidence interval [0.666-0.835], P < 0.001) to 0.841 ([0.773-0.910], P < 0.001) and from 0.793 ([0.716-0.871], P < 0.001) to 0.834 ([0.762-0.905], P < 0.001), respectively.

Conclusions: Hsa_circ_0054633 presented a certain diagnostic capability for pre-diabetes and T2DM.

Keywords: Biomarker; Circular RNAs (circRNAs); Circulating circRNA; Microarray analysis; Pre-diabetes; Type 2 diabetes mellitus (T2DM).

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Case-Control Studies
  • Cohort Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis*
  • Diabetes Mellitus, Type 2 / genetics
  • Down-Regulation
  • Female
  • Humans
  • Male
  • Microarray Analysis
  • Middle Aged
  • Prediabetic State / blood*
  • Prediabetic State / diagnosis*
  • Prediabetic State / genetics
  • Prognosis
  • RNA / blood*
  • RNA, Circular
  • Sensitivity and Specificity


  • Biomarkers
  • RNA, Circular
  • RNA