Introduction: Among macrovascular diabetes complications, CAD has been associated with diabetes in numerous studies beginning with the Framingham study. Many recent studies have shown that the risk of myocardial infarction (MI) in people with diabetes is equivalent to the risk in non-diabetic patients with a history of previous MI. Osteocalcin is the most abundant non-collagenic protein of the bone matrix. It has have been reported to be inversely associated with measures of insulin resistance, recent cross sectional and prospective studies suggest it to be an established surrogate of atherosclerosis and related cardiovascular risk.

Aim of the work: The objective of the study was to investigate the link between serum osteocalcin and hs-CRP in the different degrees of severity of atherosclerotic CAD in patients with and without T2DM.

Patients and Method: This cross-sectional study was conducted on 160 male subjects divided into four groups: Group A: 40 CAD patients with T2DM. Group B: 40 CAD patients without T2DM. Group C: 40 T2DM patients without CAD. Group D: 40 healthy control subjects. They were subjected to: complete history taking, thorough clinical examination, laboratory investigations (routine, serum insulin, osteocalcin, hs-CRP), ECG, Groups A and B were subjected to Cardiac catheterization and coronary angiography. Angiographic analysis was done using the SYNTAX score (SS).

Results: there was a statistically significant decrease in serum osteocalcin level in diabetic than non-diabetic subjects; also, there was a statistically significant negative correlation between serum osteocalcin and fasting plasma glucose and HbA1c. However there was no statistically significant difference in serum osteocalcin level between CAD and non-CAD subjects and between the 3 syntax groups of severity of CAD patients. Hs-CRP was statistically significantly higher in CAD than non-CAD patients, smokers than non-smokers, syntax group 3 than group 2, moreover, there was a statistically significant positive correlation between the hs-CRP level and the duration of CAD. There was no statistically significant difference in the serum hs-CRP level between diabetic and non-diabetic subjects.

Conclusion: Serum osteocalcin level may be considered as an indicator to the severity of glycemic control, while serum hs-CRP level as an indicator to the degree of atherosclerosis and smoking as both represent a state of chronic inflammation.

Keywords: T2DM, ACVD, osteocalcin, hs-CRP, syntax score.

1. Kannel WB, McGee DL: Diabetes and cardiovascular disease: the Framingham study. JAMA 1999; 241:2035 -8.
2. Haffner SM, Lehto S, Ronnemaa T, Pyorala K, Laakso M: Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J. 1998; 339: 229-34.
3. Buse JB, Ginsberg HN, Bakris GL, et al. Primary prevention of cardiovascular diseases in people with diabetes mellitus: a scientific statement from the American Heart Association and the American Diabetes Association. Diabetes Care 2007; 30 : 162-72
4. Szmitko PE, Wang CH, Weisel RD, de Almeida JR, Anderson TJ, Verma S. New markers of inflammation and endothelial cell activation (part I). Circulation 2003; 108:1917-23.
5. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342:836-43.
6. Ridker PM, Glynn RJ, Hennekens CH. C-reactive protein adds to the predictive value of total and HDL cholesterol in determining risk of first myocardial infarction. Circulation 1998; 97:2007-11.
7. Urena P, De Vernejoul MC. Circulating biochemical markers of bone remodeling in uremic patients. Kidney Int. 1999; 55: 2141-56.
8. Kawai M, Devlin MJ, Rosen CJ. Fat targets for skeletal health. Nat Rev 2009; 5:365–372.
9. Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B. Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009; 94:827–32.
10. Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U, Mellstrom D. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res. 2009; 24:785–91.
11. Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, Yano S, Sugimoto T. Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab 2009; 94:45– 9.
12. Tanko, Y. Bagger, C. Christiansen Low bone mineral density in the hip as a marker of advanced atherosclerosis in elderly women. Calcif Tissue Int, 2003; 73:15–20
13. Pennisi, S. Signorelli, S. Riccobene, G. Celotta, L. Di Pino, T. La Malfa, et al. Low bone density and abnormal bone turnover in patients with atherosclerosis of peripheral vessels Osteoporos Int. 2004; 15:pp. 389–95.
14. This email address is being protected from spambots. You need JavaScript enabled to view it..
15. Lee AJ, Hodges S, Eastell R. Measurement of osteocalcin. Ann Clin Biochem 2000; 37:432– 46.
16. Burtis CA, Ashwood ER, Bruns DE. Teitz textbook of clinical chemistry and molecular diagnosis Ed. ST.Louis. Elsevier Saunders Company 2006; pp (868-75, 797-801, 903-801, 604-7, 543-5, 648-708).
17. Sianos G, Morel MA, Kappetein AP, et al. The SYNTAX score: an ngiographic tool grading the complexity of CAD. EuroInterv 2005; 1: 219-27.
18. Valgimigli M, Serruys PW, Tsuchida K, et al. Cyphering the complexity of coronary artery disease using the syntax score to predict clinical outcome in patients with three-vessel lumen obstruction undergoing percutaneous coronary intervention. Am J Cardiol 2007; 99(8):1072-81.
19. Chakrabarti AK and Gibson CM: The Syntax Score:Usefulness, Limitations and Future directions. The Journal of invasive cardiology 2011; 23:(12).
20. Szulc P, Kaufman JM, Delmas PD: Biochemical assessment of bone turnover and bone fragility in men. Osteoporos Int 2007; 18: 1451-61.
21. Midtby M, Magnus JH, Joakimsen RM: The Tromso Study: a population-based study on the variation in bone formation markers with age, gender, anthropometry and season in both men and women. Osteoporos Int 2001;12: 835-43..
22. Ardawi MS, Maimani AA, Bahksh TA, Rouzi AA, Qari MH, Raddadi RM: Reference intervals of biochemical bone turnover markers for Saudi Arabian women: a cross-sectional study. Bone 2010; 47: 804-14.
23. Wei S, Winzenberg T, Laslett LL, Venn A, Jones G: Oral contraceptive use and bone. Curr Osteoporos Rep 2011; 9: 6-11.
24. Garnero P, Sornay-Rendu E, Delmas PD: Decreased bone turnover in oral contraceptive users. Bone 1995; 16: 499-503.
25. Hannon R, Blumsohn A, Naylor K, Eastell R: Response of biochemical markers of bone turnover to hormone replacement therapy: impact of biological variability. J Bone Miner Res 1998; 13: 1124-33..
26. Adami S, Bianchi G, Brandi ML, et al. Determinants of bone turnover markers in healthy premenopausal women. Calcif Tissue Int 2008; 82: 341-7.
27. Ginty F, Flynn A, Cashman KD: The effect of short-term calcium supplementation on biochemical markers of bone metabolism in healthy young adults. Br J Nutr 1998; 80: 437-43.
28. Pietschmann P, Woloszczuk W, Panzer S, Kyrle P & Smolen J (1988) Decreased serum osteocalcin levels in phenprocoumon-treated patients. J Clin Endocrinol Metab 1998; 66: 1071–74.
29. Clifford J. Rosen, Katherine J. Motyl No Bones About It: Insulin modulates skeletal remodeling cell 2010:142:198-200
30. Ernesti M, D’Onofrio, L. Lauria, A. et al. Osteocalcin levels are inversely associated with Hba1c and BMI in adult subjects with long-standing type 1 diabetes J Endocrinol Invest 2014; 37: 661.
31. Mi Zhou1, Xiaojing Ma1 , Huating Li1 ,et al. Serum osteocalcin concentrations in relation to glucose and lipid metabolism in Chinese individuals European Journal of Endocrinology 2009; 161: 723–9.
32. Qingqing Wang, Beibei Zhang, Yulan Xu et al. The Relationship between Serum Osteocalcin Concentration and Glucose Metabolism in Patients with Type 2 Diabetes Mellitus. International Journal of Endocrinology 2013; Article ID 842598.
33. Leopold JA, Am Hear Assoc Inc. 2012, 5, 605–614.
34. Idelevich A, Rais Y, Ornan EM. Bone Gla protein increases HIF-1α-dependent glucose metabolism and induces cartilage and vascular calcification. Arterioscler Thromb Vasc Biol 2011;31:e55–e71.
35. Tataru MC, Heinrich J, Junker R, et al. C-reactive protein and the severity of atherosclerosis in myocardial infarction patients with stable angina pectoris. Eur Heart J 2000; 21:1000–8.
36. O’Keefe JH, Conn RD, Lavie CJ, Bateman TM. The new paradigm for coronary artery disease: altering risk factors, atheroscl-erotic plaques, and clinical prognosis. Mayo Clin Proc 1996;71:957–65
37. King DE, Mainous AG 3rd, Buchanan TA, and. Pearson W.S. 2003. C-reactive protein and glycemic control in adults with diabetes. Diabetes Care 2003; 26(5): 1535–39.

Asmaa kamal Eldine Elshobaky

Departments of Internal Medicine,

Institute of Medical Research, Alexandria University, Egypt