title: Inactive Matrix Gla-Protein and Arterial Stiffness in Type 2 Diabetes Mellitus.
abstract: BACKGROUND
  Large artery stiffness is increased in diabetes mellitus and causes an excessive pulsatile load to the heart and to the microvasculature. The identification of pathways related to arterial stiffness may provide novel therapeutic targets to ameliorate arterial stiffness in diabetes. Matrix Gla-Protein (MGP) is an inhibitor of vascular calcification. Activation of MGP is vitamin K dependent. We hypothesized that levels of inactive MGP (dephospho-uncarboxylated MGP; dp-ucMGP) are related to arterial stiffness in type 2 diabetes.
  
  
  METHODS
  We enrolled a multiethnic cohort of 66 participants with type 2 diabetes. Carotid-femoral pulse wave velocity (CF-PWV) was measured with high-fidelity arterial tonometry (Sphygmocor Device). Dp-ucMGP was measured with ELISA (VitaK; The Netherlands).
  
  
  RESULTS
  The majority of the participants were middle-aged (62 ± 12 years), male (91%), and had a history of hypertension (82%). Average hemoglobin A1C was 7.2% (55 mmol/mol). Mean dp-ucMGP was 624 ± 638 pmol/l and mean CF-PWV was 11 ± 4 m/sec. In multivariable analyses, dp-ucMGP was independently related to African American ethnicity (β = -0.24, P = 0.005), warfarin use (β = 0.56, P < 0.001), and estimated glomerular filtration rate (eGFR, β = -0.32, P < 0.001). Dp-ucMGP predicted CF-PWV (β = 0.40, P = 0.011), even after adjustment for age, gender, ethnicity, mean arterial pressure, eGFR, and warfarin use.
  
  
  CONCLUSIONS
  In our cross-sectional analysis, circulating dp-ucMGP was independently associated with CF-PWV in type 2 diabetes. This suggests that deficient vitamin K-dependent activation of MGP may lead to large artery stiffening and could be targeted with vitamin K supplementation in the patients with diabetes.
authors.affiliation: Cardiology Division, Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
authors.forename: Mayank
authors.initials: M
authors.lastname: Sardana
authors.affiliation: Department of Medicine, Corporal Michael J. Crescenz VA MC, Philadelphia, Pennsylvania, USA.|Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Izzah
authors.initials: I
authors.lastname: Vasim
authors.affiliation: Department of Medicine, Corporal Michael J. Crescenz VA MC, Philadelphia, Pennsylvania, USA.|Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Swapna
authors.initials: S
authors.lastname: Varakantam
authors.affiliation: Department of Medicine, Corporal Michael J. Crescenz VA MC, Philadelphia, Pennsylvania, USA.
authors.forename: Uzma
authors.initials: U
authors.lastname: Kewan
authors.affiliation: Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Ali
authors.initials: A
authors.lastname: Tariq
authors.affiliation: Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Maheshwara R
authors.initials: MR
authors.lastname: Koppula
authors.affiliation: Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Amer Ahmed
authors.initials: AA
authors.lastname: Syed
authors.affiliation: Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Melissa
authors.initials: M
authors.lastname: Beraun
authors.affiliation: R&D Group, VitaK, Maastricht University, Maastricht, The Netherlands.
authors.forename: Nadja E A
authors.initials: NE
authors.lastname: Drummen
authors.affiliation: R&D Group, VitaK, Maastricht University, Maastricht, The Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.affiliation: Department of Medicine, Corporal Michael J. Crescenz VA MC, Philadelphia, Pennsylvania, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Akers
authors.affiliation: Department of Medicine, Corporal Michael J. Crescenz VA MC, Philadelphia, Pennsylvania, USA; Julio.chirinos@uphs.upenn.edu.|Cardiology Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine and Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Julio A
authors.initials: JA
authors.lastname: Chirinos
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood*; D003430:Cross-Sectional Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D063177:Pulse Wave Analysis; D014481:United States / Q000453:epidemiology; D061205:Vascular Calcification / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D059289:Vascular Stiffness / Q000502:physiology*; D055815:Young Adult; D000097568:Matrix Gla Protein
chemical_list: D015415:Biomarkers; D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein
keywords: Matrix Gla-Protein; arterial stiffness; blood pressure; diabetes mellitus; hypertension; pulse wave velocity; vitamin K.