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

Abstract

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.