Clinical Study of Dickkopf-Related Protein 1 and its Relation with Biomarkers of Bone Resorption in Patients with Metabolic Syndrome
Abstract:
Metabolic syndrome (MetS) is a
global health concern, with potential complications affecting bone health.
Dickkopf-1 (DKK1) may serve as a marker for MetS progression, particularly when
analyzed alongside other bone metabolism markers such as Bone Gamma Osteocalcin
(BGP-OST), calcitonin, and intact parathyroid hormone (I-PTH). To evaluate the
correlations between DKK1 levels and bone metabolism markers (BGP-OST,
calcitonin, and I-PTH) in patients with MetS, this case-control study included
88 participants (60 MetS patients and 28 healthy controls). Based on data
distribution, biomarker levels were analyzed using one-way ANOVA or
Kruskal-Wallis H tests. Correlations were assessed using Spearman’s test, with
p < 0.05 considered statistically significant. The diagnostic utility of
DKK1 was evaluated using ROC curve analysis. No significant differences were
observed between MetS patients and controls for DKK1, I-PTH, or calcitonin
levels, whereas BGP-OST levels were significantly higher in MetS patients (p
< 0.05). In MetS patients, DKK1 showed a significant negative correlation
with calcitonin, while BGP-OST had a significant positive correlation with
calcitonin. DKK1 demonstrated diagnostic potential with an AUC of 0.758 and a
4.11 ng/mL cut-off value. DKK1 is significantly correlated with calcitonin and
shows diagnostic utility for MetS. Elevated BG-OST levels in MetS patients
further suggest its potential role in bone metabolism alterations associated
with MetS progression.
References:
[1].
Azrak, H. I., & Sarhat, E. R. (2026).
Serum Klotho as a feasible diagnostic biomarker for metabolic syndrome in Iraqi
adults aged over 50 years. Journal of Associated Medical Sciences, 59(2),
178–186. retrieved from https://he01.tci-thaijo.org/index.php/bulletinAMS/article/view/283498
[2]. Al
Ghadeer HA, AlRamadan MS, Al Amer MM, Alshawaf MJ, Alali FJ, Bubshait AA,
Alramadhan MA, Almurayhil Z, Aldandan NS, AlKhamis MA, AlHaddad HA, AlOmair A.
Vitamin D Serum Levels in Type 2 Diabetic Patients: A Cross-Sectional Study.
Cureus. 2022 Feb 24;14(2):e22558.
[3]. Toaama,
H.R., Sarhat, E.R., Mohammed, H.S. Metformin modulated adipokines biochemical
markers in type 2 diabetes patients. Georgian Medical News, 2024, 350(5),
pp. 95–97
[4]. Salim
J.Khalaf, Gadeer Hatem Aljader, Thuraia Rifaat Sarhat. (2021). Anti-diabetic
effect of Aqueous Extract of Medicago Sativa with Enhanced Histopathology of
Pancreas in Alloxan Induced Diabetic Rats. P J M H S .2021;.15(2): 492- 496.
[6]. Sarhat,
E., Wadi, S. A., Sedeeq, B., Sarhat, T. R., Jasim, N. Study of
histopathological and biochemical effect of Punica granatum L.
extract on streptozotocin -induced diabetes in rabbits. Iraqi Journal
of Veterinary Sciences, 2019; 33(2): 189-194. doi:
10.33899/ijvs.2019.125523.1045 .
[7].
Zbaar, S.,khalaf, S.
Association of C-Reactive Protein with Risk of Complications of diabetic
nephropathy. Egyptian Journal of Chemistry, 2022; 65(8): 181-186. doi:
10.21608/ejchem.2021.99957.4868.
[8].
Sarhat ER, Rmaid ZJ,
Jabir TH (2020) Changes of salivary interleukine17, Apelin, Omentin and Vaspin
levels in normal subjects and diabetic patients with chronic periodontitis, Ann
Trop Med & Pub Health; 23:S404.
[9].
Zoch, M. L., Clemens, T. L., Riddle, R.
C., 2016, New insights into the biology of osteocalcin. Bone,82:42–49.
[10]. Tay
Donovan, Y. K., Bilezikian, J. P., 2024, Interactions between PTH and
adiposity: appetizing possibilities. Journal of Bone and Mineral Research,
zjae056. https://doi.org/10.1093/jbmr/zjae056
[11]. Kiriakopoulos,
A., Giannakis, P., Menenakos, E., 2022, Calcitonin: current concepts and
differential diagnosis. Therapeutic Advances in Endocrinology and Metabolism,
13:20420188221099344.
[12]. Viswanath, A., Vidyasagar, S., Amrutha Sukumar, C., 2023, Osteocalcin and
Metabolic Syndrome. Clinical Medicine Insights: Endocrinology and
Diabetes, 16:11795514231206728. https://doi.org/10.1177/11795514231206729
[13]. Ugurlu,
I., Akalin, A., Yorulmaz, G., 2022, The Association of Serum Osteocalcin Levels
with Metabolic Parameters and Inflammation in Postmenopausal Women with
Metabolic Syndrome. Metabolic Syndrome and Related Disorders, 20(4):219–223. https://doi.org/10.1089/met.2021.0074
[14]. Expert
Panel on Detection, 2001, Executive summary of the third report of the National
Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and
treatment of high blood cholesterol in adults (adult treatment panel III).
JAMA, 285(19):2486–2497. https://doi.org/10.1001/jama.285.19.2486
[15]. Farmanfarma,
K., et al., 2021, Incidence of and factors associated with metabolic syndrome,
south-east Islamic Republic of Iran. Eastern Mediterranean Health Journal,
27(11):1084–1091.
[16]. Zamil,
A. H., Amin, S. S., 2022, The prevalence of metabolic syndrome among university
students in Wasit, Iraq. Saudi Medical Journal, 43(11):1240–1247. https://doi.org/10.15537/smj.2022.43.11.20220558
[17]. Nikoloski,
Z., 2023, Obesity in Middle East, in Metabolic Syndrome: A Comprehensive
Textbook, Ahima, R. S. (Ed.), Springer International Publishing, Cham, pp.
65–80. https://doi.org/10.1007/978-3-031-40116-9_6
[18]. Ilyas,
K. H., Tratsiakova, V. M., 2021, The Relationship Between Body Mass Index and Biochemical
Parameters in Type 2 Diabetes Mellitus in Nineveh City in Iraq. NVEO – Natural
Volatiles & Essential Oils Journal, 2021:8112–8127.
[19]. Li, S.,
et al., 2023, Dickkopf1 (DKK1) as a Potential Biomarker in Polycystic Ovary
Syndrome and Insulin Resistance: A Cross-Sectional Study. International
Journal of Molecular Sciences, 25(12):6330. https://doi.org/10.21203/rs.3.rs-2988034/v1
[20]. Kamel,
A. A., et al., 2022, The Role of Vitamin D, DKK1, Hepcidin and Oxidative Stress
Biomarkers in Type 2 Diabetes Mellitus Patients with and Without Diabetic
Nephropathy. The Egyptian Journal of Hospital Medicine, 89(2):7137–7146.
https://doi.org/10.21608/ejhm.2022.273057
[21]. Liu,
X., et al., 2021, Associations of Osteocalcin Forms with Metabolic Syndrome and
Its Individual Components in Older Men: The Health in Men Study. The Journal of
Clinical Endocrinology & Metabolism, 106(9):e3506–e3518. https://doi.org/10.1210/clinem/dgab358
[22]. Kumar,
V., et al., 2023, Association of serum osteocalcin with beta cell function,
insulin resistance, and glycemic parameters in south Indian type 2 diabetic
subjects. International Journal of Diabetes in Developing Countries,
43(3):469–475. https://doi.org/10.1007/s13410-022-01087-y
[23]. Taher,
Z. M., Ahmed, S. N., 2023, Estimation of serum calcitonin, phosphate, and
calcium in type 2 diabetes mellitus. Zanco Journal of Medical Sciences,
27(2):205–212.
[24]. Alemzadeh,
R., Kichler, J., 2012, Parathyroid Hormone Is Associated with Biomarkers of
Insulin Resistance and Inflammation, Independent of Vitamin D Status, in Obese
Adolescents. Metabolic Syndrome and Related Disorders, 10(6):422–429.
https://doi.org/10.1089/met.2012.0056.
[25]. Elsurer,
R., Afsar, B., Guner, E., Yildiz, I., 2011, Targeting Parathyroid Hormone Level
in Diabetic Patients with Stage 3 to 5 Chronic Kidney Disease: Does Metabolic
Syndrome Matter? Journal of Renal Nutrition, 21(3):219–225. https://doi.org/10.1053/j.jrn.2010.04.006
[26]. Ministrini,
S., et al., 2020, Determinants of High Parathyroid Hormone Levels in Patients with
Severe Obesity and Their Relationship with the Cardiometabolic Risk Factors,
Before and After a Laparoscopic Sleeve Gastrectomy Intervention. Obesity
Surgery, 30(6):2225–2232. https://doi.org/10.1007/s11695-020-04453-z
[27]. Baron,
R., Kneissel, M., 2013, WNT signaling in bone homeostasis and disease: from
human mutations to treatments. Nature Medicine, 19(2):179–192. https://doi.org/10.1038/nm.3074
[28]. Karsenty,
G., Ferron, M., 2012, The contribution of bone to whole-organism physiology. Nature,
481(7381):314–320. https://doi.org/10.1038/nature10763
[29]. Khosla,
S., Hofbauer, L. C., 2017, Osteoporosis treatment: recent developments and
ongoing challenges. The Lancet Diabetes & Endocrinology,
5(11):898–907. https://doi.org/10.1016/S2213-8587(17)30188-2
[30]. Seibel,
B. A., 2016, Cephalopod Susceptibility to Asphyxiation via Ocean Incalescence,
Deoxygenation, and Acidification. Physiology, 31(6):418–429. https://doi.org/10.1152/physiol.00061.2015
