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  • Research article
  • Open Access

Phylloquinone supplementation improves glycemic status independent of the effects of adiponectin levels in premonopause women with prediabetes: a double-blind randomized controlled clinical trial

  • 1,
  • 1Email author,
  • 2,
  • 1Email author,
  • 3,
  • 4 and
  • 5
Journal of Diabetes & Metabolic Disorders201514:1

  • Received: 6 July 2014
  • Accepted: 28 December 2014
  • Published:



Vitamin K, as a cofactor in the gamma carboxylation of certain glutamic acid (Gla) residues, has been related to glucose metabolism and insulin sensitivity. Osteocalcin, also known as bone γ-carboxyglutamic acid, increases β-cell proliferation as well as insulin and adiponectin secretion, which improve glucose tolerance and insulin sensitivity. Thus, the purpose of the present study was to examine the possible role of adiponectin as a mediator of glucose homeostasis following phylloquinone supplementation in premonopause women with prediabetes.


Eighty two women were randomized to consume vitamin k1 supplement (n = 39) or placebo (n = 43) for four weeks. Participants in vitamin K1 treatment group received one pearl softgel capsule containing 1000 micrograms phylloquinone while the placebo group received one placebo capsules daily for four weeks. The Blood samples were collected at baseline and after a four-week intervention to quantify osteocalcin, adiponectin, leptin and relevant variables.


Phylloquinone supplementation significantly increased serum adiponectin concentration (1.24 ± 1.90 compared with −0.27 ± 1.08 μg/ml), and did not alter total osteocalcin (0.50 ± 4.11 compared with 0.13 ± 1.85 ng/ml) and leptin (−0.29 ± 8.23 compared with −1.15 ± 5.25 ng/ml) compared with placebo. Adjustments for total osteocalcin and adiponectin using analysis of covariance (ANCOVA) did not affect the association of glycemic status with related variables.


In conclusion our study demonstrated that phylloquinone supplementation improved glycemic status in premonopausal prediabetic women independent of adiponectin.

Trial registration

This trial was registered in Iranian Registry of Clinical Trials with ID number of IRCT2013120915724N1.


  • Phylloquinone
  • Vitamin K1
  • Osteocalcin
  • Adiponectin
  • Prediabetes


Vitamin K is a fat-soluble vitamin that functions as a cofactor in the gamma carboxylation of certain glutamic acid (Gla) residues of vitamin K dependent proteins such as osteocalcin [1]. Studies in animal models showed osteocalcin (OC), an extracellular matrix component secreted by osteoblast in the bone, to be the mediator of energy metabolism in bone, pancreas and adipose tissue. In addition, OC in its undercarboxylated form (ucOC) also enhanced insulin sensitivity by up-regulating adiponectin expression in adipose tissues [2,3]. Also, Circulating undercarboxylated osteocalcin is an index of the vitamin K status decreases in response to vitamin K supplementation [4]. Several epidemiological studies have examined the association of vitamin K intake and glycemic status and insulin homeostasis. Higher intake of vitamin k also vitamin k supplementation has been associated to reduction in insulin resistance and improved glycemic status [5-10]. These findings are in contrast to some other studies which, based on animal models, anticipate reduction in ucOC levels by increasing vitamin k intake and hence results in adverse effects on glycemic status. Therefore, it is likely that vitamin K exerts its influence on glycemic status through other mechanisms.Therefore, in this study the effect of vitamin K supplementation on osteocalcin and adiponectin and consequently their impact on glucose and insulin homeostasis was investigated.



A randomized, double-blinded, placebo controlled clinical trial was designed conducted over a total period of four weeks. This clinical trial was approved by the Ethics Committee of Ahvaz Jundishapur University of Medical Sciences. Written informed consent was obtained from all study participants. Premenopausal women with diagnosed prediabetes with ages 22 to 45 years and body mass index (BMI) of 18.5 to 30 kg/m2 were eligible for the study. Subjects were recruited based on the results of a standard 75-g Oral Glucose Tolerance Test (OGTT) at screening (blood drawn in the 0 and 120 min), according to the American Diabetes Association criteria [11]: Predibetes (PDM) was diagnosed according to the criteria established by the American Diabetes Association, i.e., impaired fasting glucose (IFG) (100 < fasting plasma glucose (FPG) < 126) or impaired Glucose test (IGT) (140 < glucose120 min <200).

A total of 82 prediabetes women met the inclusion criteria. None of the subjects suffered rheumatic, thyroid, parathyroid, kidney, or liver disease, pregnancy, lactation, menopause and drugs known to influence glucose, vitamin k and bone metabolism like insulin and glucose, lipid-lowering drugs, warfarin, corticosteroids, vitamin and mineral supplements within six months. Overall, 82 women were randomized to consume vitamin k1supplement (n = 39) or placebo (n = 43) for four weeks. Participants in vitamin K1 treatment group received one pearl softgel capsule containing 1000 micrograms phylloquinone (DSM Nutritional Products, Inc, Switzerland) while the placebo group received one placebo capsules (Barij Essence Co. Iran) daily for four weeks. Placebo capsules were similar in color, shape, size appearance, and packaging and were indistinguishable for participants and investigators. The participants were asked to maintain their habitual food consumption, body weight and physical activity pattern throughout the study and not to consume any supplements other than the one provided to them by the investigator. Dietary intake was assessed using a three-day food record consisting of three non-consecutive days, including two week days and one weekend day. The dietary records were based on estimated values in household measurements. To obtain nutrient intakes of participants on the basis of these 3-d food diaries, we used Nutritionist IV software (First Databank) modified for Iranian foods. The short form of IPAQ consists of seven questions assessing the frequency and duration of participation in vigorous, moderate and walking activity and the time spent sitting during the last week was used to determine physical activity levels [12]. The Persian translation of this questionnaire has previously been validated [13].

Assessment of variables

Body mass index and body fat were measured before and after the intervention. Body weight was measured to the nearest 0.1 kg after overnight fasting, without shoes and wearing minimal clothing, by the use of a digital scale (Seca). Height was measured to the nearest 0.1 cm by using a non-stretched tape measure (Seca). BMI was calculated as weight in kilograms divided by height in meters squared (kg/m2 ). The body fat was measured by OMRON BF 306 (Dalian, China) body fat monitor using bioelectric impedance. The Blood samples (10 ml) were collected at baseline and after a four-week intervention. After an overnight fast, 75 g OGTT was given to each subject between 8 a.m. and 10 a.m. Plasma glucose was determined at times 0 and 120 min after OGTT on the same day. Then the remaining separated serum stored at −70 C before analysis in the laboratory of Ahvaz Jundishapur University of Medical Sciences. Serum carboxylated and undercarboxylated osteocalcin (cOC and ucOC) were measured blood serum using Takara Bio Inc., EIA kits (MK118 and MK111, respectively, Bio Inc., Japan,). Total OC (tOC) was estimated as the sum of cOC and ucOC [14]. Adiponectin and leptin were quantitatively determined using a commercially available enzyme immunoassay (EIA) kit from Boster (china). Serum insulin (INS) was assayed by using an ELISA kit (Q-1-DIAPLUS, USA); Fasting blood glucose (FBG) and 2-h post-OGTT glucose were measured by auto-analyser (Hitachi, USA); hemoglobin A1C (HbA1c) was measured with HLC-723G8 (Tosoh Co., Tokyo, Japan) by high performance liquid chromatography (HPLC). Insulin resistance was calculated with HOMA-IR, which was defined as: HOMA-IR = [FPS (mg/DL)*fasting insulin (FINS (μU/ml)]/405. Basal insulin secretion which was calculated by using the following formula HOMA-%B:360*FINS(μU/ml)/(FPG-63) [15]. Quantitative insulin sensitivity check index (QUICKI) were calculated on the basis of suggested formulas: 1/[log (Insulin μU/ml) + log (Glucose mg/DL)] [16].

Statistical analyses

Data are expressed as means ± SDs. The normality of data distribution was assessed by using the Kolmogorov-Smirnov goodness-of-fit test. Two-factor repeated-measures analysis of variance (ANOVA) was used to test time*group interactions, with time and treatment as factors. In case of a significant time*group interaction, a between-group comparison of changes at 4 weeks was done by Independent-samples Student’s t test analysis. When the time effect was significant, the within-group comparison of values was performed by the paired-samples t test. Differences in proportions were evaluated by using a chi-square test. ANCOVA was performed to examine the association between supplementation group and measure of insulin sensitivity and glucose. All statistical analyses were done by using the Statistical Package for Social Sciences (SPSS version 16; SPSS Inc, Chicago, IL). The P < 0.05 was considered significant.

Results and discussion


The means and standard deviations for age, weight, and BMI were 40.17 ± 4.9 years, 71 ± 6.5 kg, and 28.08 ± 1.65 kg/m 2 , respectively. Most of the women were overweight and BMI distribution was not significantly different between two groups. According to the IPAQ questionnaire, the both groups had the same low level of physical activity. Table 1 shows the baseline and end-of-trial characteristics of the participants. Table 2 shows their dietary intakes of relevant nutrients. No significant difference existed between phylloquinone and placebo groups. Baseline values of total osteocalcin, adiponectin, leptin, FBS, 2-h post-OGTT glucose, fasting and 2-h post-OGTT insulin have been shown in Table 3. The time effects were statistically significant on adiponectin, FBS, 2-h post-OGTT glucose and 2-h post-OGTT insulin. Also the time*group interaction effects on adiponectin and 2-h post-OGTT glucose were significant (all P, 0.001). Intake of phylloquinone supplement led to significant decrease in 2 h post-OGTT glucose (−10.87 ± 27.41 compared with 1.20 ± 18.63 mg/dl), 2 h post-OGTT insulin level (−17.46 ± 44.97 compared with 5.88 ± 23.65 μIU/ml) and a significant increase in serum adiponectin concentration (1.24 ± 1.90 compared with −0.27 ± 1.08 μg/ml) compared with placebo. We did not find any significant effect of phylloquinone supplementation on total osteocalcin, leptin and related glycemic and insulin variables. To evaluate the effect of each of the total osteocalcin and adiponectin on the changes of glucose and insulin levels between groups, we adjusted them for tOC and adiponectin (Table 4).
Table 1

General characteristics of premenopausal women with PDM who received either vitamin K1 supplements or placebo


Placebo group (n = 43)

Phylloquinone group (n = 39)

P value

Age (y)

40.09 ± 4.65

40.25 ± 5.32


Weight (kg) at study baseline

71.09 ± 6.59

71.21 ± 6.47


Weight (kg) at end of trial

71 ± 6.76

70.72 ± 6.39


BMI (18.5-24.9 kg/m2) at study baseline




BMI (18.5-24.9 kg/m2) at the end of trial




BMI (25–29.9 kg/m2) ) at study baseline




BMI (25–29.9 kg/m2) at the end of trial




FM (%) at study baseline

38.55 ± 3.99

38.77 ± 3.86


FM (%) at end of trial

38.57 ± 4.10

38.46 ± 4.05


HbA1C (%) at study baseline

5.91 ± 0.49

5.81 ± 0.64


All values are means ± SDs.

*Obtained from independent-samples t test.

**Obtained from chi-square test.

Table 2

Dietary intakes of prediabetic women who received either vitamin K1 supplements or placebo throughout the study


Placebo group (n = 43)

Vitamin K1 group (n = 39)

P value 1

Energy (kcal/d)

1769 ± 275

1819 ± 272


Carbohydrate (g/d)

243.12 ± 37.76

249.60 ± 39.20


Protein (g/d)

75.04 ± 12.75

77.56 ± 11.60


Fat (g/d)

64.90 ± 10.05

66.32 ± 10.34


Vitamin k (μg/d)

57.16 ± 19.03

62.69 ± 15.45


Vitamin D (mg/d)

3.7 ± 1.6

4.06 ± 1.67


Calcium (mg/d)

719.38 ± 261

677.0 ± 237.97


All values are means ± SDs.

1Obtained from independent-samples t test.

Table 3

Metabolic variables, biomarkers of insulin resistance and comparison of changes within and between placebo and phylloquinone groups


Placebo group (n = 43)

Phylloquinone group (n = 39)








P value 1

Total Osteocalcin (ng/ml)

11.95 ± 5.76

12.08 ± 5.65

0.13 ± 1.85

14.50 ± 5.81

15.01 ± 6.51

0.50 ± 4.11


leptin (ng/ml)

26.78 ± 10.33

25.62 ± 10.21

−1.15 ± 5.25

28.59 ± 9.61

28.29 ± 9.86

−0.29 ± 8.23


Adiponectin (μg/ml)

8.81 ± 1.54

8.54 ± 1.87

−0.27 ± 1.08

9.19 ± 1.80

10.44 ± 1.20*

1.24 ± 1.90


FBS (mg/DL)

106.69 ± 13.63

105.20 ± 12.41

−1.48 ± 10.37

107.66 ± 10.72

104 ± 11.25*

−3.12 ± 9.22


2-h-post-OGTT glucose (mg/DL)

155.27 ± 15.97

156.48 ± 26.44

1.20 ± 18.63

143.84 ± 35.30

132.97 ± 27.37*

−10.87 ± 27.41


FINS (μIU/ml)

23.83 ± 12.08

23.80 ± 8.28

−0.02 ± 8.92

20.74 ± 9.90

20.56 ± 8.04

−0.18 ± 5.92


2-h-post-OGTT INS (μIU/ml)

106.55 ± 46.96

112.43 ± 53.19

5.88 ± 23.65

97.80 ± 54.50

80.34 ± 42.24*

−17.46 ± 44.97


All values are means ± SDs. *Different from week 0, P < 0.05; OGTT, oral glucose tolerance test; INS, Insulin; FINS, Fasting insulin; FBS, Fasting blood sugar.

1Obtained from independent-samples t test.

Table 4

Adjusted changes in metabolic variables in prediabetic women who received either vitamin K1 supplements or placebo


Placebo group (n = 43)

Vitamin K1 group (n = 39)

P value 1

FBS (mg/DL)



1.48 ± 1.50

−3.12 ± 1.57



−1.46 ± 1.51

−3.13 ± 1.58



−1.97 ± 1.59

−2.59 ± 1.67


2-h post-OGTT glucose (mg/DL)



1.20 ± 3.54

−10.87 ± 3.71



1.36 ± 3.54

−11.04 ± 3.71



2.48 ± 3.74

−12.28 ± 3.95


FINS (μIU/ml)



−0.02 ± 1.16

−0.18 ± 1.22



0.003 ± 1.17

−0.21 ± 1.23



-.039 ± 1.24

−0.16 ± 1.31


2-h post-OGTT insulin (μIU/ml)



5.88 ± 5.40

−17.46 ± 5.67



5.69 ± 5.41

−17.25 ± 5.60



9.90 ± 5.58

−21.88 ± 5.89





−0.05 ± 0.32

−0.22 ± .34



-.05 ± 0.32

−0.22 ± 0.34



−0.06 ± 0.34

−0.20 ± 0.36





−5.42 ± 14.49

14.95 ± 15.21



4.84 ± 14.50

14.31 ± 15.23



−7.10 ± 15.42

16.80 ± 16.28





−0.004 ± 0.002

−0.001 ± 0.002



−0.004 ± 0.002

−0.001 ± 0.002



−0.004 ± 0.002

−0.00 ± 0.003


All values are means ± SEs. Model 1 show original raw data, Model 2 was adjusted for tOC; Model 3 was adjusted for adiponectin; tOC, Total osteocalcin; FBS, Fasting blood sugar; OGTT, Oral glucose tolerance test; FINS, Fasting insulin; HOMA-IR, Homeostasis model assessment insulin resistance index; HOMA-B, Homeostatic model assessment–β cell function; QUICKI, Quantitative insulin sensitivity check index. 1Obtained from ANCOVA.


Several epidemiological studies have investigated the association between vitamin K intake and glycemic status. For instance, in a cross-sectional study of 2719 adults 26–81 years of age, Yoshida et al. [7] showed that higher intake of vitamin K was associated with better insulin sensitivity and lower post-challenge glucose levels. In addition, Beulens JW et al. [5], found that higher intakes of vitamin K were associated with reduced risk of type 2 diabetes. In another study with similar results it was reported in a National Health and Nutrition Examination Survey (NHANES) 1999–2004 that vitamin K intake in the highest, compared with the lowest, quintile was associated with lower prevalence of hyperglycemia as a component of metabolic syndrome [6]. However, the exact mechanisms underlying the associations between vitamin k intakes, glycemic status and insulin homeostasis still remain unknown. One finding which could possibly help shed light on the mechanism has been reported by Lee et al. [3]. They demonstrated that osteocalcin, a vitamin-K-dependent protein in bone, is involved in glucose metabolism by increasing insulin secretion and cell proliferation in pancreatic β-cells and by upregulating the expression of the adiponectin gene in adipocytes, thus improving insulin sensitivity. This study was devised as a first study of its kind, to explore the impacts of the carboxylation of Osteocalcin by vitamin K and the mediation effects of adiponectin in prediabetic, premonopause women. In this study, it was observed that phylloquinone supplementation for four weeks significantly increased serum adiponectin, decreased 2-h post-OGTT glucose and did not change the other related variables compared with placebo. In contrast, Knapen MH [17] found that Supplementation with vitamin K did not affect circulating adiponectin concentrations. Choi et al. [18] also reported that no significant alterations were seen in fasting plasma glucose and adiponectin concentrations in serum with 4 weeks Vitamin K2 Supplementation in healthy young male subjects. Cross sectional studies have also pointed to the relationships between these variables. Kanazawa et al. [19] found that that ucOC/OC ratio positively correlated with serum adiponectin level in men. Reinehr T [20] studied obese children and found no significant relationship between adiponectin and osteocalcin. Meanwhile, another study failed to show such an association between adiponectin and osteocalcin [21].

In the current study, analysis of covariance was performed to determine the role of either osteocalcin or adiponectin in glucose and insulin homeostasis. It was observed that adjustments for total steocalcin and adiponectin did not alter the associations of the related variables to glycemic status. Along the same lines, Shea et al. [22] reported that the strength of the association between total osteocalcin and carboxylated osteocalcin with HOMA-IR was somewhat attenuated after adiponectin was accounted for; therefore, they concluded that the association between total osteocalcin and carboxylated osteocalcin with HOMA-IR may depend partially on adiponectin. Chen X et al. [23] reported that the negative association between HOMA-IR and tOC remained significant after being controlled for adiponectin. In Hwang YC et al. study [24] on adult subjects, it was reported that although the circulating osteocalcin level was associated with improved glucose tolerance and insulin secretion, this was independent of the plasma adiponectin level.

Although these studies and their contradictory results have considered the relationships between adiponectin and osteocalcin, it seems vitamin K probably influence Glycemic status through other mechanisms.


Finally although this study could not provide the underlying mechanism we speculate that vitamin K1 supplementation could modulate glycemic status by mechanism other total osteocalcin and adiponectin in premonopausal prediabetes women. In conclusion our study demonstrated that phylloquinone supplementation improved glycemic status in premenopausal prediabetic women independent of adiponectin.



This paper is issued from the Ph.D thesis of Hamid Rasekhi, and the financial support was provided by Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences (Grant number NRC-9108). This trial was registered in Iranian Registry of Clinical Trials with ID number of IRCT2013120915724N1.

Authors’ Affiliations

Nutrition and Metabolic Diseases Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Hyperlipidemia Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Department of Food Hygiene, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
Department of Biostatistics and Epidemiology, School of Health, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
Diabetes Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran


  1. Shanahan CM, Proudfoot D, Farzaneh-Far A, Weissberg PL. The role of Gla proteins in vascular calcification. Critical reviews in eukaryotic gene expression. 1998;8(3–4):357–75.PubMedView ArticleGoogle Scholar
  2. Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci U S A. 2008;105(13):5266–70.PubMed CentralPubMedView ArticleGoogle Scholar
  3. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–69.PubMed CentralPubMedView ArticleGoogle Scholar
  4. Booth SL, Lichtenstein AH, O’Brien-Morse M, McKeown NM, Wood RJ, Saltzman E, et al. Effects of a hydrogenated form of vitamin K on bone formation and resorption. Am J Clin Nutr. 2001;74(6):783–90.PubMedGoogle Scholar
  5. Beulens JW, van der A D, Grobbee DE, Sluijs I, Spijkerman AM, van der Schouw YT. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care. 2010;33(8):1699–705.PubMed CentralPubMedView ArticleGoogle Scholar
  6. Pan Y, Jackson RT. Dietary phylloquinone intakes and metabolic syndrome in US young adults. J Am Coll Nutr. 2009;28(4):369–79.PubMedView ArticleGoogle Scholar
  7. Yoshida M, Booth SL, Meigs JB, Saltzman E, Jacques PF. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am J Clin Nutr. 2008;88(1):210–5.PubMedGoogle Scholar
  8. Yoshida M, Jacques PF, Meigs JB, Saltzman E, Shea MK, Gundberg C, et al. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care. 2008;31(11):2092–6.PubMed CentralPubMedView ArticleGoogle Scholar
  9. Ibarrola-Jurado N, Salas-Salvado J, Martinez-Gonzalez MA, Bullo M. Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease. Am J Clin Nutr. 2012;96(5):1113–8.PubMedView ArticleGoogle Scholar
  10. Juanola-Falgarona M, Salas-Salvado J, Estruch R, Portillo MP, Casas R, Miranda J, et al. Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk. Cardiovascular diabetology. 2013;12:7.PubMed CentralPubMedView ArticleGoogle Scholar
  11. American Diabetic Associations. Diagnosis and classification of diabetes mellitus. Diab Care. 2011;34 Suppl 1:62–9.View ArticleGoogle Scholar
  12. International Physical Activity Questionnaire. IPAQ Research Committee Guidelines for the Data Processing and Analysis of the International Physical Activity Questionnaire (IPAQ)-Short and Long Forms. 2005. Accessed 10 Jun 2014
  13. Moghaddam MHBAF, Jafarabadi MA, Allahverdipour H, Nikookheslat SD, Safarpour S. The Iranian Version of International Physical Activity Questionnaire (IPAQ) in Iran: content and construct validity, factor structure, internal consistency and stability. World Applied Sciences Journal. 2012;18(8):1073–80.Google Scholar
  14. Suh HS, Hwang IC, Lee KS, Kim KK. Relationships between serum osteocalcin, leptin and the effect of weight loss by pharmacological treatment in healthy, nonsmoking Korean obese adults. Clin Chim Acta. 2013;418:17–21.PubMedView ArticleGoogle Scholar
  15. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985;28(7):412–9.PubMedView ArticleGoogle Scholar
  16. Duncan MH, Singh BM, Wise PH, Carter G, Alaghband-Zadeh J. A simple measure of insulin resistance. Lancet. 1995;346(8967):120–1.PubMedView ArticleGoogle Scholar
  17. Knapen MH, Schurgers LJ, Shearer MJ, Newman P, Theuwissen E, Vermeer C. Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight. Br J Nutr. 2012;108(6):1017–24.PubMedView ArticleGoogle Scholar
  18. Choi HJ, Yu J, Choi H, An JH, Kim SW, Park KS, et al. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care. 2011;34(9):e147.PubMed CentralPubMedView ArticleGoogle Scholar
  19. Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S, et al. Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int. 2011;22(1):187–94.PubMedView ArticleGoogle Scholar
  20. Reinehr T, Roth CL. A new link between skeleton, obesity and insulin resistance: relationships between osteocalcin, leptin and insulin resistance in obese children before and after weight loss. Int J Obes (Lond). 2010;34(5):852–8.View ArticleGoogle Scholar
  21. Abseyi N, Siklar Z, Berberoglu M, Hacihamdioglu B, Savas Erdeve S, Ocal G. Relationships between osteocalcin, glucose metabolism, and adiponectin in obese children: Is there crosstalk between bone tissue and glucose metabolism? Journal of clinical research in pediatric endocrinology. 2012;4(4):182–8.PubMed CentralPubMedView ArticleGoogle Scholar
  22. Shea MK, Gundberg CM, Meigs JB, Dallal GE, Saltzman E, Yoshida M, et al. Gamma-carboxylation of osteocalcin and insulin resistance in older men and women. Am J Clin Nutr. 2009;90(5):1230–5.PubMed CentralPubMedView ArticleGoogle Scholar
  23. Chen X, Wu Y, Liu L, Tian H, Yu X. Osteocalcin is inversely associated with glucose levels in middle-aged Tibetan men with different degrees of glucose tolerance. Diabetes Metab Res Rev. 2014;30(6):476–82.PubMedView ArticleGoogle Scholar
  24. Hwang YC, Jeong IK, Ahn KJ, Chung HY. Circulating osteocalcin level is associated with improved glucose tolerance, insulin secretion and sensitivity independent of the plasma adiponectin level. Osteoporos Int. 2012;23(4):1337–42. doi: 10.1007/s00198-011-1679-x. Epub 2011 Jun 9.PubMed CentralPubMedView ArticleGoogle Scholar


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