Body mass index and insulin resistance in healthy adults: Associations with plasma osteocalcin, phylloquinone levels, and dietary vitamin K intake

Main Article Content

Yasemin Ertaş Öztürk
Makbule Gezmen Karadağ
Müjde Aktürk
Nevin Şanlıer


insulin resistance, body mass index, osteocalcin, vitamin K, phylloquinone


The skeletal system is considered an endocrine organ today. Associations between bone Gla proteins, body mass index and insulin resistance are intriguing novel field due to being possible explanations for the interactions between bone and endocrine system. The aim of the present study was to investigate the associations between insulin resistance and body mass index (BMI) with plasma osteocalcin, phylloquinone levels and dietary vitamin K intakes in healthy non-obese adults. This cross-sectional study was conducted with 77 healthy non-obese adults. Anthropometric measurements and 24-hour food consumption record were taken from each individual. Blood glucose, insulin, osteocalcin (OC), undercarboxylated osteocalcin (ucOC), vitamin K levels were analyzed. The homeostasis model assessment for insulin resistance (HOMA-IR) value was calculated. Multiple linear regression models were performed using the backward method in order to determine the significant predictors of BMI and HOMA-IR. Mean age and BMI of the participants were 31.7±5.6 years and 24.6±3.04 kg/m2 respectively. After multiple regression analysis, BMI, dietary vitamin K intake and phylloquinone were significant predictors of HOMA-IR. Furthermore, ucOC and triglyceride were significant predictors of BMI. No significant association between OC levels and HOMA-IR values were shown. In healthy non-obese adults, ucOC may be related to decreasing BMI. Our data do not support that increased OC has a beneficial role against insulin resistance. Dietary vitamin K intake may have a protective effect on insulin resistance. Further studies should examine the clinical importance of these findings.


Download data is not yet available.
Abstract 242 | PDF Downloads 126


1. Karsenty G, Olson EN. Bone and Muscle Endocrine Functions: Unexpected Paradigms of Inter-organ Communication. Cell 2016; 164: 1248-1256.
2. Hauschka PV, Lian JB, Cole D et al. Osteocalcin and matrix Gla protein: vitamin K-dependent proteins in bone. Physiol Rev 1989; 69: 990-1047.
3. Lee NK, Sowa H, Hinoi E et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456-469.
4. Patti A, Gennari L, Merlotti D et al. Endocrine actions of osteocalcin. Int J Endocrinol 2013; 2013: 846480.
5. O'Connor EM, Durack E. Osteocalcin: The extra-skeletal role of a vitamin K-dependent protein in glucose metabolism. J Nutr Intermed Metab 2017; 7: 8-13.
6. Kanazawa I, Yamaguchi T, Yamauchi M et al. Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 2011; 22: 187-194.
7. Foresta C, Strapazzon G, De Toni L et al. Evidence for osteocalcin production by adipose tissue and its role in human metabolism. J Clin Endocrinol Metab 2010; 95: 3502-3506.
8. Centi AJ, Booth SL, Gundberg CM et al. Osteocalcin carboxylation is not associated with body weight or percent fat changes during weight loss in post-menopausal women. Endocrine 2015; 50: 627-632.
9. Wang Q, Zhang B, Xu Y et al. The Relationship between Serum Osteocalcin Concentration and Glucose Metabolism in Patients with Type 2 Diabetes Mellitus. Int J Endocrinol 2013; 2013: 842598.
10. Sarkar P, Choudhury A. Relationships between serum osteocalcin levels versus blood glucose, insulin resistance and markers of systemic inflammation in central Indian type 2 diabetic patients. Eur Rev Med Pharmacol Sci 2013; 17: 1631-1635.
11. Polgreen LE, Jacobs DR, Nathan BM et al. Association of osteocalcin with obesity, insulin resistance, and cardiovascular risk factors in young adults. Obesity 2012; 20: 2194-2201.
12. Ngarmukos C, Chailurkit LO, Chanprasertyothin S et al. A reduced serum level of total osteocalcin in men predicts the development of diabetes in a long-term follow-up cohort. Clin Endocrinol (Oxf) 2012; 77: 42-46.
13. Kanazawa I, Yamaguchi T, Tada Y et al. Serum osteocalcin level is positively associated with insulin sensitivity and secretion in patients with type 2 diabetes. Bone 2011; 48: 720-725.
14. Aoki A, Muneyuki T, Yoshida M et al. Circulating osteocalcin is increased in early-stage diabetes. Diabetes Res Clin Pract 2011; 92: 181-186.
15. Im JA, Yu BP, Jeon JY et al. Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta 2008; 396: 66-69.
16. Shearer M, Bolton-Smith C. The UK food data-base for vitamin K and why we need it. Food Chem 2000; 68: 213-218.
17. Shearer MJ, Fu X, Booth SL. Vitamin K nutrition, metabolism, and requirements: current concepts and future research. Adv Nutr 2012; 3: 182-195.
18. Binkley NC, Krueger DC, Engelke JA et al. Vitamin K supplementation reduces serum concentrations of under-γ-carboxylated osteocalcin in healthy young and elderly adults. Am J Clin Nutr 2000; 72: 1523-1528.
19. Binkley NC, Krueger DC, Kawahara TN et al. A high phylloquinone intake is required to achieve maximal osteocalcin γ-carboxylation. Am J Clin Nutr 2002; 76: 1055-1060.
20. Sakamoto N, Nishiike T, Iguchi H et al. Possible effects of one week vitamin K (menaquinone-4) tablets intake on glucose tolerance in healthy young male volunteers with different descarboxy prothrombin levels. Clin Nutr 2000; 19: 259-263.
21. Sakamoto N, Wakabayashi I, Sakamoto K. Low vitamin K intake effects on glucose tolerance in rats. Int J Vitam Nutr Res 1999; 69: 27-31.
22. Choi HJ, Yu J, Choi H et al. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes care 2011; 34: e147.
23. Ohsaki Y, Shirakawa H, Hiwatashi K et al. Vitamin K suppresses lipopolysaccharide-induced inflammation in the rat. Biosci Biotechnol Biochem 2006; 70: 926-932.
24. Shea MK, Booth SL, Massaro JM et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol 2008; 167: 313-320.
25. Beulens JW, van der AD, Grobbee DE et al. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes care 2010; 33: 1699-1705.
26. Yoshida M, Booth SL, Meigs JB et al. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am J Clin Nutr 2008; 88: 210-215.
27. Beslenme Bilgi Sistemi (BeBiS) bilgisayar yazılım programı versiyon 7.
28. Matthews D, Hosker J, Rudenski A et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419.
29. SPSS. SPSS Inc. Statistical Package for the Social Sciences. Chicago, IL; USA, 2001.
30. Bao Y, Ma X, Yang R et al. Inverse relationship between serum osteocalcin levels and visceral fat area in Chinese men. Int J Clin Endocrinol Metab 2013; 98: 345-351.
31. Ma X, Chen F, Hong H et al. The Relationship between Serum Osteocalcin Concentration and Glucose and Lipid Metabolism in Patients with Type 2 Diabetes Mellitus-The Role of Osteocalcin in Energy Metabolism. Ann Nutr Metab 2015; 66: 110-116.
32. Liatis S, Sfikakis P, Tsiakou A et al. Baseline osteocalcin levels and incident diabetes in a 3-year prospective study of high-risk individuals. Diabetes Metab J 2014; 40: 198-203.
33. Dagogo-Jack S, Fanelli C, Paramore D et al. Plasma leptin and insulin relationships in obese and nonobese humans. Diabetes 1996; 45: 695-698.
34. Minocci A, Savia G, Lucantoni R et al. Leptin plasma concentrations are dependent on body fat distribution in obese patients. Int J Obes Relat Metab Disord 2000; 24: 1139-1144.
35. Silha JV, Krsek M, Skrha JV et al. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003; 149: 331-335.
36. Zuo H, Shi Z, Yuan B et al. Association between serum leptin concentrations and insulin resistance: a population-based study from China. PloS one 2013; 8: e54615.
37. Yamauchi T, Kamon J, Waki H et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7: 941-946.
38. Saleem U, Mosley TH, Kullo IJ. Serum osteocalcin is associated with measures of insulin resistance, adipokine levels, and the presence of metabolic syndrome. Arterioscler Thromb Vasc Biol 2010; 30: 1474-1478.
39. Shiraki M, Tsugawa N, Okano T. Recent advances in vitamin K-dependent Gla-containing proteins and vitamin K nutrition. Osteoporos Sarcopenia 2015; 1: 22-38.
40. Shea M, Benjamin E, Dupuis J et al. Genetic and non-genetic correlates of vitamins K and D. Eur J Clin Nutr 2009; 63: 458.
41. Sakamoto N, Nishiike T, Iguchi H et al. Relationship between acute insulin response and vitamin K intake in healthy young male volunteers. Diabetes Nutr Metab 1999; 12: 37-41.
42. Manna P, Kalita J. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review. Nutrition 2016; 32: 732-739.
43. Shea MK, Dallal GE, Dawson-Hughes B et al. Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am J Clin Nutr 2008; 88: 356-363.
44. Ohsaki Y, Shirakawa H, Miura A et al. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor kappaB through the repression of IKKalpha/beta phosphorylation. J Nutr Biochem 2010; 21: 1120-1126.
45. Satman I, Ozbey N, Boztepe H et al. Prevalence and correlates of vitamin D deficiency in Turkish adults. Endocrine Abstracts. 2013.
46. Poomthavorn P, Nantarakchaikul P, Mahachoklertwattana P et al. Effects of correction of vitamin D insufficiency on serum osteocalcin and glucose metabolism in obese children. Clin Endocrinol (Oxf) 2014; 80: 516-523.
47. Mitchell DM, Leder BZ, Cagliero E et al. Insulin secretion and sensitivity in healthy adults with low vitamin D are not affected by high-dose ergocalciferol administration: a randomized controlled trial. Am J Clin Nutr 2015; 102: 385-392.
48. Fuleihan GE-H, Baddoura R, Habib RH et al. Effect of vitamin D replacement on indexes of insulin resistance in overweight elderly individuals: a randomized controlled trial. Am J Clin Nutr 2016; 104: 315-323.