Diabetes confersin vitrocalcific potential on serum which associates within vivovascular calcification.
Although vascular calcification (VC) is prevalent in Type 2 diabetes mellitus (T2DM), underlying mechanisms remain unclear. Neither is it known whether T2DM confers calcific potential (CP) on serum, enabling it to induce VC outside the disease milieu. We, therefore, investigated the CP of serum from controls and subjects with T2DM with and withoutin vivoVC.Samples from 20 healthy controls and 44 age- and sex-matched patients with T2DM with modification of diet in renal disease estimated glomerular filtration rate (MDRD-4 eGFR) > 60 ml·min-1were analysed for CP using rat aortic smooth muscle cellsin vitroCT scans of femoral arteries identified individuals within vivocalcification. Serum from subjects with T2DM revealed significantly greater CP than controls. This was further enhanced in the presence ofin vivoVC. Addition of β-glycerophosphate (β-GP) plus CaCl2increased the CP of T2DM serum but not of controls. Along with age, CP was an independent predictor of the presence of VC. In receiver operator curve (ROC) analysis, CP was a significant predictor of femoral arterial VC (C-statistic 0.70:P=0.009). The distribution of CP was bimodal around a cutoff of 100 nmoles of Ca2+protein mg-1, with a higher proportion of Type 2 diabetes subjects within vivocalcification (T2DM+) sera above the cutoff value. This group also showed elevated levels of osteoprotegerin (OPG) and matrix Gla protein (MGP). Diabetes confers CP on the serum which is enhanced by the presence ofin vivoVC. The CP acquired may be dependent on levels of OPG and MGP. These findings may be clinically relevant for early identification of individuals at risk of VC and for informing therapeutic strategies.
School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K.
Ashish
A
Patidar
School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K.|Renal Unit, Lister Hospital, Coreys Mill Lane, Stevenage SG1 4AB, U.K.
Dhruv K
DK
Singh
School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K.
Shori
S
Thakur
Department of Diabetes and Endocrinology, QEII Hospital, Howlands, Welwyn Garden City, AL7 4HQ, U.K.
Peter
P
Winocour
School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K.|Renal Unit, Lister Hospital, Coreys Mill Lane, Stevenage SG1 4AB, U.K.
Ken
K
Farrington
School of Life and Medical Sciences, University of Hertfordshire, College Lane, Hatfield, Hertfordshire AL10 9AB, U.K. a.baydoun@herts.ac.uk.
Anwar R
AR
Baydoun
D000368:Aged; D002135:Calcium-Binding Proteins / Q000097:blood; D016022:Case-Control Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications*; D016326:Extracellular Matrix Proteins / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008297:Male; D008875:Middle Aged; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D053244:Osteoprotegerin / Q000097:blood; D061205:Vascular Calcification / Q000097:blood* / Q000209:etiology* / Q000503:physiopathology; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D053244:Osteoprotegerin; D000097568:Matrix Gla Protein
Type 2 diabetes; matrix Gla protein; osteoprotegerin; serum calcific potential; vascular aortic smooth muscle cells; vascular calcification