Ghrelin is deregulated in obesity-associated insulin resistance (IR) while visfatin features a role in glucose uptake regulation, inflammation and IR. This study aimed to conduct comparisons and correlations of ghrelin and visfatin plasma levels in nondiabetic metabolic syndrome (MetS) and MetS-prediabetic/type 2 diabetes mellitus (T2DM) patients. In a cross-sectional study of 30 normoglycemic lean subjects (control), 31 MetS subjects, and 30 MetS-prediabetic/T2DM, plasma ghrelin and visfatin were measured by colorimetric-enzymatic assays. The comparison of both biomarkers between study groups and the correlation between them as well as with participants’ adiposity, hematologic, and atherogenicity indices were conducted. Ghrelin levels (pg/mL) lacked any statistically significant difference between each of nondiabetic MetS (618.10 ± 93.22, p = 0.103) or MetS-pre/T2DM (498.17 ± 103.21, p = 0.454) vs. the normoglycemic lean control (369.38 ± 111.76). Visfatin level (ng/mL) in MetS patients with pre/T2DM (19.24 ± 2.05, p = 0.003) or without pre/T2DM (18.43 ± 1.83, p = 0.002) was significantly higher as compared to healthy controls’ (8.62 ± 2.23). There was a direct ghrelin-visfatin correlation in the whole study population as well as in both MetS and MetS-pre/T2DM arms (p < 0.001). In nondiabetic MetS patients, ghrelin and visfatin proportionally correlated with waist/hip ratio (WHR; p = 0.032 vs. p = 0.008, respectively) while ghrelin correlated directly with BMI (p = 0.034). In MetS-pre/T2DM, visfatin correlated directly with body adiposity index (p = 0.039) but inversely with WHR (p = 0.011), while ghrelin and visfatin directly correlated with mean platelet volume (p = 0.025 vs. p = 0.030, respectively) and ghrelin proportionally correlated with platelet/lymphocyte ratio (p = 0.034). In effect, ghrelin and visfatin molecular interplays with adiposity and blood indices in the MetS derangements may present potential pharmacotherapeutic targets in metabolism and prediabetes anomalies.
Visfatin Ghrelin Prediabetes Metabolic syndrome
This is a preview of subscription content, log in to check access.
We sincerely thank all patients who participated in the study.
The research was funded by the Deanship of Academic Research & Quality Assurance, The University of Jordan.
Compliance with ethical standards
An informed consent was obtained from all included subjects. The study started after obtaining approval from the Scientific Research Committee at the School of Pharmacy, the Deanship of Academic Research, the University of Jordan and approval from the JUH Institutional Review Board (IRB) committee.
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with animals performed by any of the authors.
Holman RR. Type 2 diabetes mellitus in 2012: optimal management of T2DM remains elusive. Nat Rev Endocrinol. 2013;9:67–8.CrossRefGoogle Scholar
Ajlouni K, Khader YS, Batieha A, Ajlouni H, El-khateeb M. An increase in prevalence of diabetes mellitus in Jordan over 10 years. J Diabetes Complicat. 2008;22:317–24.CrossRefGoogle Scholar
Whiting DR, Guariguata L, Weil C, Shaw J. IDF diabetes atlas: global estimates of the prevalence of diabetes for 2011 and 2030. Diabetes Res Clin Pract. 2011;94:311–21.CrossRefGoogle Scholar
Abu-Zaiton A, Al-Fawwaz A. Prevalence of diabetes, obesity, hypertension and associated factors among students of Al-albayt University, Jordan. World J Med Sci. 2013;9:49–54.Google Scholar
Khader Y, Bateiha A, El-Khateeb M, Al-Shaikh A, Ajlouni K. High prevalence of the MetS among Northern Jordanians. J Diabetes Complicat. 2007;21:214–9.CrossRefGoogle Scholar
American Diabetes Association (ADA). Standards of medical care in diabetes. Diabetes Care. 2016;39:S1–2.CrossRefGoogle Scholar
Grundy SM, Cleeman JI, Daniels SR, Donato KA, Eckel RH, Franklin BA, et al. Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute scientific statement. Circulation. 2005;112:2735–52.CrossRefGoogle Scholar
Stern MP, Williams K, Gonzalez-Villalpando C, Hunt KJ, Haffner SM. Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care. 2004;27:2676–81.CrossRefGoogle Scholar
Deng Y, Scherer PE. Adipokines as novel biomarkers and regulators of the metabolic syndrome. Ann N Y Acad Sci. 2010;1212:E1–E19.CrossRefGoogle Scholar
Jung UJ, Choi M-S. Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci. 2014;15(4):6184–223.CrossRefGoogle Scholar
Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T, et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab. 2001;86:4753–8.CrossRefGoogle Scholar
Yang J, Brown MS, Liang G, Grishin NV, Goldstein JL. Identification of the acyltransferase that octanoylates ghrelin, an appetite-stimulating peptide hormone. Cell. 2008;132:387–96.CrossRefGoogle Scholar
Marzullo P, Verti B, Savia G, Walker GE, Guzzaloni G, Tagliaferri M, et al. The relationship between active ghrelin levels and human obesity involves alterations in resting energy expenditure. J Clin Endocrinol Metab. 2004;89:936–9.CrossRefGoogle Scholar
Poykko SM, Kellokoski E, Horkko S, Kauma H, Kesaniemi YA, Ukkola O. Low plasma ghrelin is associated with insulin resistance, hypertension, and the prevalence of T2DM. Diabetes. 2003;52:2546–53.CrossRefGoogle Scholar
Nagaya N, Uematsu M, Kojima M, Date Y, Nakazato M, Okumura H, et al. Elevated circulating level of ghrelin in cachexia associated with chronic heart failure: relationships between ghrelin and anabolic/catabolic factors. Circulation. 2001a;104:2034–8.CrossRefGoogle Scholar
Nagaya N, Uematsu M, Kojima M, Ikeda Y, Yoshihara F, Shimizu W, et al. Chronic administration of ghrelin improves left ventricular dysfunction and attenuates development of cardiac cachexia in rats with heart failure. Circulation. 2001b;104:1430–5.CrossRefGoogle Scholar
Chang L, Ren Y, Liu X, Li WG, Yang J, Geng B, et al. Protective effects of ghrelin on ischemia/reperfusion injury in the isolated rat heart. J Cardiovasc Pharmacol. 2004;43:165–70.CrossRefGoogle Scholar
Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science. 2005;307:426–30.CrossRefGoogle Scholar
Beltowski J. Apelin and visfatin: unique “beneficial” adipokines upregulated in obesity. Med Sci Monit. 2006;12:RA112–9.Google Scholar
Sartori C, Lazzeroni P, Merli S, Patianna VD, Viaroli F, Cirillo F, et al. From placenta to polycystic ovarian syndrome: the role of adipokines. Mediat Inflamm. 2016;2016:4981916.CrossRefGoogle Scholar
Moschen AR, Kaser A, Enrich B, Mosheimer B, Theurl M, Niederegger H, et al. Visfatin, an adipocytokine with proinflammatory and immunomodulating properties. J Immunol. 2007;178:1748–58.CrossRefGoogle Scholar
Ahmed MB, Ismail MIA, Meki A-RM. Relation of osteoprotegerin, visfatin and ghrelin to metabolic syndrome in type 2 diabetic patients. Int J Health Sci. 2015;9:127–39.Google Scholar
Nadeem A, Naveed AK, Hussain MM, Raza S. Cut-off values of anthropometric indices to determine insulin resistance in Pakistani adults. J Pak Med Assoc. 2013;63:1220.Google Scholar
Geliebter A, Atalayer D, Flancbaum L, Gibson C. Comparison of body adiposity index (BAI) and body mass index (BMI) with estimations of % body fat in clinically severe obese women. Obesity (Silver Spring). 2013;21(3):493–8.CrossRefGoogle Scholar
Kanthe PS, Patil BS, Bagali SH, Deshpande A, Shaikh G, Aithala M. Atherogenic index as a predictor of cardiovascular risk among women with different grades of obesity. International Journal of Collaborative Research on Internal Medicine & Public Health. 2012;4:1767–74.Google Scholar
Sharifi F, Yamini M, Esmaeilzadeh A, Mousavinasab N, Shajari Z. Acylated ghrelin and leptin concentrations in patients with type 2 diabetes mellitus, people with prediabetes and first degree relatives of patients with diabetes, a comparative study. Journal of Diabetes and Metabolic Disorders. 2013;12:51.CrossRefGoogle Scholar
Chen S, Zuo X, Li Y, Jiang T, Zhang N, Dai F, et al. Ghrelin is a possible new predictor associated with executive function in patients with type 2 diabetes mellitus. J Diabetes Investig. 2016;8(3):306–13.CrossRefGoogle Scholar
Akdoğan M, Ustundag-Budak Y, Huysal K. The association of hematologic inflammatory markers with atherogenic index in type 2 diabetic retinopathy patients. Clin Ophthalmol (Auckland, N.Z.). 2016;10:1797–801.CrossRefGoogle Scholar
Baltacı D, Tuncel M, Cetinkaya M, Gunduz M, Ozbey Z, Admis O, et al. Evaluation of visfatin in patients with obesity, metabolic syndrome, insulin resistance and impaired glucose tolerance; case-control study. Acta Medica Anatolia. 2016;4:61–7.CrossRefGoogle Scholar
Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M. The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia. 2006;49:1909–14.CrossRefGoogle Scholar
Pagano C, Pilon C, Olivieri M, Mason P, Fabris R, Serra R, et al. Reduced plasma visfatin/pre-B cell colony enhancing factor in obesity is not related to insulin resistance in humans. J Clin Endocrinol Metab. 2006;91:3165–70.CrossRefGoogle Scholar
Berndt J, Klöting N, Kralisch S, Kovacs P, Fasshauer M, Schön MR, et al. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes. 2005;54:2911–6.CrossRefGoogle Scholar
Kamińska A, Kopczyńska E, Bronisz A, Zmudzińska M, Bieliński M, Borkowska A, et al. An evaluation of visfatin levels in obese subjects. Endokrynol Pol. 2010;61:169–73.Google Scholar
El-Shafey EM, El-Naggar GF, Al-Bedewy MM, El-Sorogy H. Is there a relationship between visfatin level and type 2 diabetes mellitus in obese and non obese patients? J Diabetes Metab. 2012;S11:001.Google Scholar
Filippatos TD, Derdemezis CS, Kiortsis DN, Tselepis AD, Elisaf MS. Increased plasma levels of visfatin/pre-B cell colony-enhancing factor in obese and overweight patients with metabolic syndrome. J Endocrinol Investig. 2007;30:323–6.CrossRefGoogle Scholar
Olszanecka-Glinianowicz M, Kocełak P, Nylec M, Chudek J, Zahorska-Markiewicz B. Circulating visfatin level and visfatin/insulin ratio in obese women with metabolic syndrome. Arch Med Sci. 2012;8:214–8.CrossRefGoogle Scholar