Impaired bone matrix glycoprotein pattern is associated with increased cardio-metabolic risk profile in patients with type 2 diabetes mellitus

J Endocrinol Invest. 2019 May;42(5):513-520. doi: 10.1007/s40618-018-0941-x. Epub 2018 Aug 21.


Purpose: Osteopontin (OPN), osteoprotegerin (OPG) and osteocalcin (OC) are matrix glycoproteins which mediate bone mineralization; moreover, their effects on glucose/insulin homeostasis have recently been demonstrated. Higher circulating OPN and OPG levels have been associated with the presence of insulin resistance, atherosclerosis and coronary heart disease. No data are available on contextual changes of these markers in type 2 diabetes mellitus (T2DM). Therefore, aims of this study were to evaluate serum OPN, OPG and OC levels in T2DM patients and their clinical correlates.

Methods: We recruited 83 consecutive T2DM patients referring to our diabetes outpatient clinics at Sapienza, University of Rome, and 71 non-diabetic sex and age-comparable subjects as a control group. Study population underwent metabolic characterization and carotid ultrasound for intima-media thickness measurement. Plasma OPN, OPG and OC were measured by MILLIPLEX Multiplex Assays Luminex.

Results: T2DM patients had significantly higher circulating OPN and OPG levels than controls (14.3 ± 13.6 vs 10.6 ± 13.7 ng/ml p < 0.001, 0.70 ± 0.60 vs 0.54 ± 4.1 ng/ml, p = 0.02) while OC levels were similar in the two cohorts (6.35 ± 5.8 vs 7.80 ± 7.0 ng/ml, p = n.s). OPN and OPG positively correlated with greater systolic blood pressure (SBP) values, HOMA-IR and HOMA-β, and with the presence of dyslipidemia and carotid atherosclerosis. The association between greater OPN and OPG levels and SBP was independent from possible confounders (both p = 0.01).

Conclusions: Circulating OPN and OPG levels are increased in T2DM patients and identify a particularly unfavourable metabolic profile, mostly expressed by higher SBP. Bone peptides may represent novel markers of vascular stress and accelerated atherosclerosis in diabetes, constituting a possible tool for cardiovascular risk stratification in diabetes.

Keywords: Glycoproteins; Osteocalcin; Osteopontin; Osteoprotegerin; Type 2 diabetes.

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood*
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / etiology
  • Case-Control Studies
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications*
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Metabolic Syndrome / blood*
  • Metabolic Syndrome / diagnosis
  • Metabolic Syndrome / etiology
  • Metabolome
  • Middle Aged
  • Osteocalcin / blood
  • Osteopontin / blood*
  • Osteoprotegerin / blood*
  • Prognosis
  • Risk Factors


  • BGLAP protein, human
  • Biomarkers
  • Osteoprotegerin
  • SPP1 protein, human
  • TNFRSF11B protein, human
  • Osteocalcin
  • Osteopontin