The low levels of bone morphogenic protein-4 and its antagonist noggin in type 2 diabetes

Hormones (Athens). 2018 Jun;17(2):247-253. doi: 10.1007/s42000-018-0041-5. Epub 2018 Jun 26.


Objective: Bone morphogenic protein-4 (BMP-4) is a proinflammatory cytokine which is controlled by BMP-4 antagonists. Our aim was to investigate the levels of BMP-4 and its antagonists, noggin and matrix Gla protein (MGP), in prediabetes and diabetes.

Design: One hundred and forty-two type 2 diabetic, 32 prediabetic, and 58 control subjects participated in this cross-sectional study. BMP-4, noggin, and MGP were measured with the ELISA method.

Results: There was a significant difference between the three groups in relation to sex, hypertension, fasting plasma glucose, HbA1c, lipid profiles, and diastolic blood pressure (p < 0.05). BMP-4 levels were significantly lower in the diabetic group compared to the control group (108.5 and 127.5 ng/mL, respectively, p < 0.001 diabetes vs. control). Noggin levels were significantly lower in the diabetic group compared to the prediabetic and control groups (10.5, 11.5, and 12.0 ng/mL, as median, respectively, p < 0.001; diabetes vs. control, p = 0.002; diabetes vs. prediabetes). BMP-4 was associated significantly with noggin in the entire study population (ß coefficient = 0.796, p < 0.001). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve was 0.708 (95% CI 0.551-0.864, p = 0.011) for BMP-4 levels. The optimal cutoff value of BMP-4 for detecting albuminuria was 118.5 ng/mL for which sensitivity was 71.4% and specificity was 66.4%.

Conclusions: BMP-4 and noggin levels were lower in the diabetic group. High BMP-4 levels were significantly associated with albuminuria. Further studies are warranted to determine the role of BMP-4 in the pathogenic processes underlying albuminuria and hyperglycemia in patients with type 2 diabetes.

Keywords: Antagonists; BMP-4; Urinary albumin excretion.

MeSH terms

  • Adult
  • Aged
  • Albuminuria / urine*
  • Bone Morphogenetic Protein 4 / blood*
  • Calcium-Binding Proteins / blood*
  • Carrier Proteins / blood*
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / urine
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Prediabetic State / blood*
  • Prediabetic State / urine


  • BMP4 protein, human
  • Bone Morphogenetic Protein 4
  • Calcium-Binding Proteins
  • Carrier Proteins
  • Extracellular Matrix Proteins
  • matrix Gla protein
  • noggin protein