Fetuin-A – Alpha2-Heremans-Schmid Glycoprotein: From Structure to a Novel Marker of Chronic Diseases Part 2. Fetuin-A – A Marker of Insulin Resistance and Related Chronic Diseases

Regina S. Komsa-Penkova 1 , Katya S. Kovacheva 2 , Georgy M. Golemanov 1 , Veselin P. Penkov 3 , Zdravka V. Radionova 4 , Galia B. Georgieva-Alexandrova 1 , and Alim V. Izmajlov 1
  • 1 Division of Biochemistry, Medical University – Pleven, Bulgaria
  • 2 Division of Medical Genetics, Medical University – Pleven, Bulgaria
  • 3 Repromed Medical Centrum – Pleven, , Bulgaria
  • 4 Division of Pedagogy and Psychology, Medical University – Pleven, Bulgaria


Fetuin-A is a secretory liver glycoprotein with multiple physiological functions such as regulation of insulin resistance, tissue calcification, bone metabolism, cellular proteolytic activity, and self-proliferative signaling.

Fetuin-A is a unique molecule which binds to the insulin receptor, modulating its sensitivity, and transducing “the physiological conditions” (serum levels of the metabolites like glucose, free fatty acids, inflammatory signals) from outside into inside the cells. Plasma fetuin-A levels correlate with reduced glucose tolerance and insulin resistance. Impaired insulin sensitivity leads to the development of metabolic syndrome, an increased risk for type 2 diabetes (T2DM), dyslipidaemias and cardiovascular diseases (CVDs). Furthermore, fetuin-A inversely correlates with inflammatory and activation biomarkers, e.g. in patients with T2DM. Thus, circulatory fetuin-A levels may have plausible predictive importance as a biomarker of risk of diabetes and negative acute phase protein. Dysregulated, it plays a crucial role in the pathogenesis of some metabolic disorders and clinical inflammatory conditions like metabolic syndrome, T2DM, CVDs, polycystic ovary syndrome (PCOS), etc.

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