We investigated the correlation between obestatin and metabolic parameters and carotid intima-media thickness (IMT) in plasma of patients with type 2 diabetes mellitus (T2DM). We collected 103 patients aged from 60 to 83 years (69.26 ± 5.83 years) form January, 2007 to May, 2009. All patients were divided into normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and T2DM according to the oral glucose tolerance test (OGTT). We found that higher levels of fasting insulin (Fins), fasting blood glucose, 2？h OGTT glucose, homeostasis model assessment of insulin resistance (HOMA-IR), low density lipoprotein cholesterol, glycated haemoglobin, and C-reactive protein (CRP), as well as lower obestatin level and higher intima-media thickness level (IMT), existed in T2DM group compared with NGT group and IGT group ( ). Also, obestatin level was independently associated with HOMA-IR and CRP, while IMT level was independently associated with HOMA-IR, triglyceride, Fins, and obestatin ( ), based on stepwise multiple regression analysis. Therefore, we deduced that the low level of plasma obestatin might be related to early arteriosclerosis in patients with T2DM via increasing IMT level, and elevated plasma obestatin levels might protect T2DM patients against carotid atherosclerosis to some extent. 1. Introduction Type 2 diabetes mellitus (T2DM) is related to a significant increase in the risk of atherosclerosis [1]. In the past several years, clinical studies have shown that high mortality in patients with T2DM is due to cardiovascular disease [2]. Besides, T2DM often coexists with dyslipidemia, coronary disease, hypertension, and visceral obesity [3, 4]. As is well known, cardiometabolic risk factors play important roles in pathophysiology of arteriosclerosis and diabetes, including hormones in the appetite and body weight regulation, adipokine (leptin, resistin, and adiponectin), ghrelin, and obestatin [5, 6]. With the development of blood glucose-lowering medications, such as lifestyle-directed interventions, insulin, sulfonylureas, and metformin, the number of treatment options available for T2DM has increased recently [7]. Besides, rosiglitazone maleate targets insulin resistance to enhance the synthesis of glucose transporters and activate adipocyte differentiation, while metformin hydrochloride can promote the lowering glucose by reducing hepatic glucose production and enhance the gluconeogenesis; by increasing peripheral glucose uptake, the combination of two drugs is effective and safe in reducing hyperglycemia in patients with T2DM [8]. Although
References
[1]
J. A. Beckman, M. A. Creager, and P. Libby, “Diabetes and atherosclerosis epidemiology, pathophysiology, and management,” Journal of the American Medical Association, vol. 287, no. 19, pp. 2570–2581, 2002.
[2]
D. Kirpichnikov and J. R. Sowers, “Diabetes mellitus and diabetes-associated vascular disease,” Trends in Endocrinology and Metabolism, vol. 12, no. 5, pp. 225–230, 2001.
[3]
K. Pyorala, M. Laakso, and M. Uusitupa, “Diabetes and atherosclerosis: an epidemiologic view,” Diabetes/Metabolism Reviews, vol. 3, no. 2, pp. 463–524, 1987.
[4]
S. M. Haffner, S. Lehto, T. R？nnemaa, K. Py？r？l？, and M. Laakso, “Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction,” The New England Journal of Medicine, vol. 339, no. 4, pp. 229–234, 1998.
[5]
é. Toussirot, G. Streit, N. U. Nguyen et al., “Adipose tissue, serum adipokines, and ghrelin in patients with ankylosing spondylitis,” Metabolism, vol. 56, no. 10, pp. 1383–1389, 2007.
[6]
J. Vendrell, M. Broch, N. Vilarrasa et al., “Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity,” Obesity Research, vol. 12, no. 6, pp. 962–971, 2004.
[7]
D. M. Nathan, “Medical management of hyperglycemia in type 2 diabetes: a consensus algorithm for the initiation and adjustment of therapy: a consensus statement of the american diabetes association and the european association for the study of diabetes,” Diabetes Care, vol. 32, no. 3, pp. e37–e38, 2009.
[8]
V. Fonseca, J. Rosenstock, R. Patwardhan, and A. Salzman, “Effect of metformin and rosiglitazone combination therapy in patients with type 2 diabetes mellitus: a randomized controlled trial,” Journal of the American Medical Association, vol. 283, no. 13, pp. 1695–1702, 2000.
[9]
D. M. Nathan, “Initial management of glycemia in type 2 diabetes mellitus,” The New England Journal of Medicine, vol. 347, no. 17, pp. 1342–1349, 2002.
[10]
S. E. Inzucchi, “Oral antihyperglycemic therapy for type 2 diabetes: scientific review,” Journal of the American Medical Association, vol. 287, no. 3, pp. 360–372, 2002.
[11]
D. C. Klonoff, J. B. Buse, L. L. Nielsen et al., “Exenatide effects on diabetes, obesity, cardiovascular risk factors and hepatic biomarkers in patients with type 2 diabetes treated for at least 3 years,” Current Medical Research and Opinion, vol. 24, no. 1, pp. 275–286, 2008.
[12]
A.-D. Cui, N.-N. Gai, X.-H. Zhang, et al., “Decreased serum obestatin consequent upon TRIB3 Q84R polymorphism exacerbates carotid atherosclerosis in subjects with metabolic syndrome,” Diabetology and Metabolic Syndrome, vol. 4, no. 1, pp. 1–5, 2012.
[13]
G. Alloatti, E. Arnoletti, E. Bassino et al., “Obestatin affords cardioprotection to the ischemic-reperfused isolated rat heart and inhibits apoptosis in cultures of similarly stressed cardiomyocytes,” American Journal of Physiology, vol. 299, no. 2, pp. H470–H481, 2010.
[14]
J. V. Zhang, P.-G. Ren, O. Avsian-Kretchmer et al., “Medicine: obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake,” Science, vol. 310, no. 5750, pp. 996–999, 2005.
[15]
S. S. Qader, R. H？kanson, J. F. Rehfeld, I. Lundquist, and A. Salehi, “Proghrelin-derived peptides influence the secretion of insulin, glucagon, pancreatic polypeptide and somatostatin: a study on isolated islets from mouse and rat pancreas,” Regulatory Peptides, vol. 146, no. 1–3, pp. 230–237, 2008.
[16]
M. Kapica, M. Zabielska, I. Puzio et al., “Obestatin stimulates the secretion of pancreatic juice enzymes through a vagal pathway in anaesthetized rats—preliminary results,” Journal of Physiology and Pharmacology, vol. 58, no. 3, pp. 123–130, 2007.
[17]
J. V. Zhang, P.-G. Ren, O. Avsian-Kretchmer et al., “Medicine: Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake,” Science, vol. 310, no. 5750, pp. 996–999, 2005.
[18]
V. Catalán, J. Gómez-Ambrosi, F. Rotellar et al., “The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus,” Clinical Endocrinology, vol. 66, no. 4, pp. 598–601, 2007.
[19]
S. Mohr-Kahaly, “New diagnostic criteria for diabetes and coronary artery disease: insights from an angiographic study,” Journal of the American College of Cardiology, vol. 37, no. 6, pp. 1543–1550, 2001.
[20]
T. Nakahara, T. Harada, D. Yasuhara et al., “Plasma obestatin concentrations are negatively correlated with body mass index, insulin resistance index, and plasma leptin concentrations in obesity and anorexia nervosa,” Biological Psychiatry, vol. 64, no. 3, pp. 252–255, 2008.
[21]
U. Gurriarán-Rodríguez, O. Al-Massadi, A. Roca-Rivada, et al., “Obestatin as a regulator of adipocyte metabolism and adipogenesis,” Journal of Cellular and Molecular Medicine, vol. 15, no. 9, pp. 1927–1940, 2011.
[22]
R. Granata, D. Gallo, R. M. Luque, et al., “Obestatin regulates adipocyte function and protects against diet-induced insulin resistance and inflammation,” The FASEB Journal, vol. 26, no. 8, pp. 3393–3411, 2012.
[23]
X. Qi, L. Li, G. Yang et al., “Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus,” Clinical Endocrinology, vol. 66, no. 4, pp. 593–597, 2007.
[24]
V. Catalán, J. Gómez-Ambrosi, F. Rotellar et al., “The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus,” Clinical Endocrinology, vol. 66, no. 4, pp. 598–601, 2007.
[25]
D. H. St-Pierre, F. Settanni, I. Olivetti et al., “Circulating obestatin levels in normal and Type 2 diabetic subjects,” Journal of Endocrinological Investigation, vol. 33, no. 4, pp. 211–214, 2010.
[26]
H. N. Hodis, W. J. Mack, L. LaBree et al., “The role of carotid arterial intima—media thickness in predicting clinical coronary events,” Annals of Internal Medicine, vol. 128, no. 4, pp. 262–269, 1998.
[27]
M. W. Lorenz, H. S. Markus, M. L. Bots, M. Rosvall, and M. Sitzer, “Prediction of clinical cardiovascular events with carotid intima-media thickness: a systematic review and meta-analysis,” Circulation, vol. 115, no. 4, pp. 459–467, 2007.
[28]
T. Temelkova-Kurktschiev, C. Koehler, E. Henkel, and M. Hanefeld, “Leukocyte count and fibrinogen are associated with carotid and femoral intima-media thickness in a risk population for diabetes,” Cardiovascular Research, vol. 56, no. 2, pp. 277–283, 2002.
[29]
G. Brohall, A. Odén, and B. Fagerberg, “Carotid artery intima-media thickness in patients with Type 2 diabetes mellitus and impaired glucose tolerance: a systematic review,” Diabetic Medicine, vol. 23, no. 6, pp. 609–616, 2006.
[30]
S. H. Kim, S. J. Lee, E. S. Kang et al., “Effects of lifestyle modification on metabolic parameters and carotid intima-media thickness in patients with type 2 diabetes mellitus,” Metabolism, vol. 55, no. 8, pp. 1053–1059, 2006.
[31]
E. J. Lee, H. J. Kim, J. M. Bae et al., “Relevance of common carotid intima-media thickness and carotid plaque as risk factors for ischemic stroke in patients with type 2 diabetes mellitus,” American Journal of Neuroradiology, vol. 28, no. 5, pp. 916–919, 2007.
[32]
E. Kellokoski, A. Kunnari, M. Jokela, S. M？kel？, Y. A. Kes？niemi, and S. H？rkk？, “Ghrelin and obestatin modulate early atherogenic processes on cells: enhancement of monocyte adhesion and oxidized low-density lipoprotein binding,” Metabolism, vol. 58, no. 11, pp. 1572–1580, 2009.
[33]
G. Alloatti, E. Arnoletti, E. Bassino et al., “Obestatin affords cardioprotection to the ischemic-reperfused isolated rat heart and inhibits apoptosis in cultures of similarly stressed cardiomyocytes,” American Journal of Physiology, vol. 299, no. 2, pp. H470–H481, 2010.
[34]
A. J. Agnew, E. Robinson, C. M. McVicar et al., “The gastrointestinal peptide obestatin induces vascular relaxation via specific activation of endothelium-dependent NO signalling,” British Journal of Pharmacology, vol. 166, no. 1, pp. 327–338, 2012.
[35]
E. Kellokoski, A. Kunnari, M. Jokela, S. M？kel？, Y. A. Kes？niemi, and S. H？rkk？, “Ghrelin and obestatin modulate early atherogenic processes on cells: enhancement of monocyte adhesion and oxidized low-density lipoprotein binding,” Metabolism, vol. 58, no. 11, pp. 1572–1580, 2009.
