Serum leptin concentration in patients with type 2 diabetes
With the increasing importance of early type 2 diabetes (DM2) and obesity detection, it is useful to reevaluate leptin role in these conditions. Our study aimed at investigating circulating leptin concentrations in a group of patients with DM2, and at assessing in detail whether leptin concentrations correlate with selected biochemical, clinical parameters and markers of systemic inflammation in patients with DM2 and in healthy volunteers. In our work, we analysed samples and data drawn from 71 patients aged 61.4 ± 11.7 years, who have been diagnosed with type 2 diabetes, as well as from a healthy control group (HC) consisting of 51 healthy subjects with a mean age of 57.8 ± 13.7 years. Therein, the concentration of leptin in the DM2 patients was significantly higher than in the HC (p < 0.01), with median value of 16.59 (IQR 8.58-33.39) ng/ml in the DM2, vs median value of 6.66 (IQR 4.52-21.40) ng/ml in the HC. In the analysis of variance, higher leptin concentrations were revealed in the DM2 group as compared to the HC, and this figure remained significant after adjusting for gender and age (p < 0.001). Moreover, it was independent of HOMA-IR (p = 0.003). However, the differences in leptin levels between the groups disappeared when additional adjustments for anthropometric parameters (BMI, waist circumference) were applied (p = 0.088). Beyond the aforementioned, significant positive correlations were found in the DM 2 group between leptin level and CRP (r=0.256; p < 0.05) and IL-6 (r = 0.345; p < 0.01). Among the selected variables, only gender and BMI were included in the predictive model explaining the variability of leptin, and, in total, were responsible for 72.6% of the original variation of the studied adipocytokine. The results of this study have led to conclusion that leptin may participate in the complex pathogenesis of DM2 and be a predictor of the development of this disease. As higher concentrations of leptin coexist with obesity, and this situation correlates positively with markers of inflammation (CRP, IL-6), leptin level, hence, should be considered in the pathogenesis of DM2.
- Department of Biochemistry Diagnostics, Medical University of Lublin, Staszica 11, 20-081 Lublin, Poland, firstname.lastname@example.org
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Beckett, LS9 7TF Leeds, UK
- Department of Endocrinology, Medical University of Lublin, Jaczewskiego 8, 20-090 Lublin, Poland
- Department of Biochemistry Diagnostics, Medical University of Lublin, Staszica 11, 20-081 Lublin, Poland
- 1. Anderlová K. et. al.: The influence of very-low-calorie-diet on serum leptin, soluble leptin receptor, adiponectin and resistin levels in obese women. Physiol. Res., 55(3), 277, 2006.
- 2. Bays H.E.: Adiposopathy is “sick fat” a cardiovascular disease? J. Am. Coll. Cardiol., 57(25), 2461, 2011.[Crossref]
- 3. Blüher M., Mantzoros C.S.: From leptin to other adipokines in health and disease: facts and expectations at the beginning of the 21st century. Metabolism, 64(1), 131, 2015.[WoS][Crossref]
- 4. Chen G.C., Qin L.Q., Ye J.K.: Leptin levels and risk of type 2 diabetes: gender-specific meta-analysis. Obes. Rev., 15(2), 134, 2014.[WoS]
- 5. Chen K. et. al.: Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat. Med., 12(4), 425, 2006.[Crossref]
- 6. Correia M.L., Rahmouni K.: Role of leptin in the cardiovascular and endocrine complications of metabolic syndrome. Diabetes Obes. Metab., 8(6), 603, 2006.[Crossref]
- 7. Dardeno T.A. et. al.: Leptin in human physiology and therapeutics. Front Neuroendocrinol., 31(3), 377, 2010.
- 8. Denroche H.C., Huynh F.K., Kieffer T.J.: The role of leptin in glucose homeostasis. J. Diabetes Investig., 3(2), 115, 2012.[WoS][Crossref]
- 9. Esteghamati A. et. al.: Association of serum leptin levels with homeostasis model assessment-estimated insulin resistance and metabolic syndrome: the key role of central obesity. Metab. Syndr. Relat. Disord. 7(5), 447, 2009.[WoS][Crossref]
- 10. Esteghamati A. et. al.: Serum visfatin is associated with type 2 diabetes mellitus independent of insulin resistant and obesity. Diabetes Res. Clin. Pract., 91(2), 154, 2011.[Crossref]
- 11. Friedewald W.T., Levy R.I., Fredrickson D.S.: Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin. Chem., 18(6), 499, 1972.
- 12. Gui Y., Silha J.V., Murphy L.J.: Sexual dimorphism and regulation of resistin, adiponectin, and leptin expression in the mouse. Obes. Res., 12(9), 1481, 2004.[Crossref]
- 13. Kershaw E.E., Flier J.S.: Adipose tissue as an endocrine organ. J. Clin. Endocrinol. Metab,. 89(6), 2548, 2004.[Crossref]
- 14. Lee J.M. et. al.: The relationship between adipokines, metabolic parameters and insulin resistance in patients with metabolic syndrome and type 2 diabetes. Int. Med. Res., 37(6), 1803, 2009.[WoS][Crossref]
- 15. Levey A.S. et. al.: Using standardized serum creatinine values in the modification of diet in the renal disease study equation for estimating glomerular filtration rate. Ann. Intern. Med., 145(4), 247, 2006.[Crossref]
- 16. Ley S.H. et. al.: Adipokines and incident type 2 diabetes in an Aboriginal Canadian population: the Sandy Lake Health and Diabetes Project. Diabetes Care, 31(7), 1410, 2008.[Crossref]
- 17. Malecha-Jedraszek A. et. al.: Concentration of adiponectin in relation to insulin resistance in patients with type 2 diabetes. Ann. UMCS Sect. DDD, 24 (4), 73, 2011.
- 18. Martos-Moreno G.Á. et. al.: Effect of weight loss on high-molecular weight adiponectin in obese children. Obesity (Silver Spring),18(12), 2288, 2010.[Crossref][WoS]
- 19. Matthews D.R. et. al.: Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28(7), 412, 1985.[Crossref]
- 20. Menon V. et. al.: Factors associated with serum leptin in patients with chronic kidney disease. Clin. Nephrol., 61(3), 163, 2004.[Crossref]
- 21. Olstad R. et. al.: Leptin in the General Population, Differences in Sex Hormones, Blood Lipids, Gender and Life Style Characteristics. The Open Behavioral Science Journal, 5, 8, 2011.
- 22. Park H.K., Ahima R.S.: Physiology of leptin: energy homeostasis, neuroendocrine function and metabolism. Metabolism, 64(1), 24, 2015.[Crossref][WoS]
- 23. Paz-Filho G. et. al.: Leptin: molecular mechanisms, systemic proinflammatory effects, and clinical implications. Arq. Bras. Endocrinol. Metabol., 56(9), 597, 2012.[Crossref]
- 24. Saginova E.A. et. al.: The role of leptin, adiponectin and insulinresistance markers in development of early stages of chronic kidney disease and atherosclerosis of carotid arteries in obese patients. Ter. Arkh., 83(6), 47, 2011.
- 25. Sáinz N. et. al.: Leptin resistance and diet-induced obesity: central and peripheral actions of leptin. Metabolism, 64(1), 35, 2015.[Crossref][WoS]
- 26. Silha J.V. et. al.: Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur. J. Endocrinol., 149(4), 331, 2003.[Crossref]
- 27. Söderberg S. et. al.: Leptin predicts the development of diabetes in Mauritian men, but not women: a population-based study. Int. J. Obes. (Lond)., 31(7), 1126, 2007.[WoS][Crossref]
- 28. Sun Q. et. al.: Leptin and soluble leptin receptor levels in plasma and risk of type 2 diabetes in U.S. women: a prospective study. Diabetes, 2010; 611, 59(3).[WoS]
- 29. Tokuyama Y. et. al.: Serum resistin level is associated with insulin sensitivity in Japanese patients with type 2 diabetes mellitus. Metabolism, 56(5), 693, 2007.[Crossref][WoS]
- 30. Wang H., Luo W., Eitzman D.T.: Leptin in thrombosis and atherosclerosis. Curr. Pharm. Des., 20(4), 641, 2014.[Crossref]
- 31. Wannamethee S.G. et. al.: Adipokines and risk of type 2 diabetes in older men. Diabetes Care, 30(5), 1200, 2007.[WoS][Crossref]
- 32. Wannamethee S.G. et. al.: Plasma leptin: associations with metabolic, inflammatory and haemostatic risk factors for cardiovascular disease. Atherosclerosis, 191(2), 18, 2007.[WoS][Crossref]
- 33. Welsh P. et. al.: Leptin predicts diabetes but not cardiovascular disease: results from a large prospective study in an elderly population. Diabetes Care, 32(2), 308, 2009.[WoS][Crossref]
- 34. Wolf G., Ziyadeh F.N.: Leptin and renal fibrosis. Contrib. Nephrol., 151, 175, 2006.
- 35. World Health Organisation: Obesity: preventing and managing the global epidemic. Report of a WHO consultation, Genewa 1997.
- 36. Zhou Y., Rui L.: Leptin signaling and leptin resistance. Front Med., 7(2), 207, 2013.[Crossref][WoS]
- 37. Zimmet P., Alberti K.G., Serrano Ríos M.: A new international diabetes federation worldwide definition of the metabolic syndrome: the rationale and the results. Rev. Esp. Cardiol., 58(12), 1371, 2005.[Crossref]
- 38. Zuo H. et. al.: Association between serum leptin concentrations and insulin resistance: a population-based study from China. PLoS One, 8(1), 1, 2013.