Growth arrest-specific protein 6 (Gas6) as a noninvasive biomarker for early detection of diabetic nephropathy

Clin Exp Hypertens. 2017;39(4):382-387. doi: 10.1080/10641963.2017.1288739. Epub 2017 May 17.


Background: To investigate the diagnostic level of cystatin C and growth arrest-specific gene 6 (Gas6) levels in elderly type 2 diabetic patients with different degrees of diabetic nephropathy (DN).

Methods: Four hundred and eighty-two old people, including 130 healthy controls, 130 normoalbuminuric diabetic patients, 122 with microalbuminuria, and 100 with macroalbuminuria, were recruited. Plasma Gas6 and serum cystatin C levels were measured.

Results: Plasma Gas6 concentration was significantly lower in diabetic patients with microalbuminuria or macroalbuminuria, as compared with diabetic subjects with normoalbuminuria; while cystatin C was significantly higher. Gas6 was inversely correlated with BMI, WHR, and HbA1c, while cystatin C was inversely correlated with urea nitrogen and creatinine. Multivariate logistic regression analysis showed that, after adjusted for established diabetes risk factors, higher plasma Gas6 was significantly associated with a decreased risk of DN, while higher serum cystatin C was significantly associated with an increased risk. Receiver operating characteristic curve analysis showed that Gas6 was better than cystatin C as a biomarker for early diagnosis and detection of DN, with a cutoff value of 9.435 ng/mL (86.1% sensitivity and 84.6% specificity).

Conclusion: Compared to cystatin C, Gas6 may be potentially a better noninvasive diagnostic biomarker for early detection of DN.

Keywords: Biomarker; cystatin C; diabetic nephropathy (DN); early detection; growth arrest-specific gene 6 (Gas6).

MeSH terms

  • Aged
  • Albuminuria / blood
  • Albuminuria / complications
  • Biomarkers / blood
  • Blood Urea Nitrogen
  • Body Mass Index
  • Case-Control Studies
  • Creatinine / blood
  • Cystatin C / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetic Nephropathies / blood*
  • Diabetic Nephropathies / diagnosis*
  • Diabetic Nephropathies / etiology
  • Early Diagnosis
  • Female
  • Glycated Hemoglobin / metabolism
  • Humans
  • Hypertension / complications
  • Intercellular Signaling Peptides and Proteins / blood*
  • Male
  • ROC Curve
  • Waist-Hip Ratio


  • Biomarkers
  • Cystatin C
  • Glycated Hemoglobin A
  • Intercellular Signaling Peptides and Proteins
  • growth arrest-specific protein 6
  • hemoglobin A1c protein, human
  • Creatinine