Determination of the Percentage of Blood Free Leptin Hormone in Diabetic Patients after Treatment with Metformin

Document Type: Original Article


Yazd Diabetes Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran


Plasma leptin exists in protein-bound and free forms, which may affect its hormonal bioactivity. The free and bound forms are changed by the body weight. The purpose of this study was to evaluate the effect of metformin on bound and free plasma leptin concentration.
Materials and Methods
Subjects recruited from Yazd Diabetes Research Centre, Yazd University of Medical Sciences. The participants were new cases of obese type 2 diabetes (BMI>30 kg/ m2). Fasting bloods samples, before and after one month treatment with metformin collected. These samples used for the purification of free leptin by HPLC method and analysis of other biochemical parameters.
The results indicated that, there was no significant difference observed between the free leptin forms before and after the one month treatment (71%±4.2 vs 72±5).
The one month treatment, reduced blood sugar in patients, but at the same time it did not have a reduction effect on the body weight. Therefore, in the free form of hormone after treatment comparing to before treatment it did not make a significant difference. This confirmed other reports which showed that the variation of free leptin depended on the body weight.


1. Mantzoros CS, Stergios J, Moschos. Leptin in search of role (s) in human physiology and pathophysilogy, Clin Endocrinol. 1997; 49:551- 567.

2. Friedman JM, Halaas JL. Leptin and the regulation of body Weight in mammals. Nature 1998; 395:763-770.

3. Friedman JM.  The function of leptin in nutrition, weight, and physiology. Metabol 2002; 52:45-48.

4. EL-Haschimi K, Lehert. Leptin resistance or why leptin fails to work in obesity. Clin Endocrinol, Diabetes 2002; 111:2-7.

5. Brabant H, Nave B, Mayr M, Behrend V, Van Harmelen, Arner P. Secretion of free and protein-bound leptin from subcutaneous adipose tissue of  lean and obese women. J Clin Endocrinol Metabol 2002; 87:366-369.

6. Laimer C F, Ebenbichler S, Kaser A, Sandhofer H, Weiss H, Nehoda F, et al. Weight loss increases soluble leptin receptor levels and the soluble receptor bound fraction of  leptin. Obes Res 2002; 10:597 - 601.

7. Gallardo C, Arribas M, Villar M, Ros J M, Carrascosa, C, Martinez,  Andres O. Are differentially expressed in adipose tissue in aged food-Restricted Rats: Effects on circulating soluble leptin receptor levels. Endocrinol 2005; 146:4934- 4942.

8. Glueck CG, Fontaine RN, Wang P, Subbiah MT, Weber K, Streicher P, et al. Metformin reduces weight, centripetal obesity, insulin, leptin, and low-density lipoprotein cholesterol in no diabetic, morbidly obese subjects with body mass index greater than 30. Metabol. 2001; 50:856-861.

9. Kiefer T, Heller RS, Leech CA, Holz GG, Habener JF. Lpetin suppression of insulin secretion by the activation of ATP-sensitive K channels in pancreatic â-cells. Diabetes 1997; 46:1087-1093.

10. Harvey J, McKenna F, Herson PS, Spanswick D, Ashford ML. Leptin activates ATP-sensitive potasium channels in the rat insulin secreting cell line. J  Physiol 1997; 504:527-735.

11. Ciaraldi TP, Kong AP, Chu NV,Kim DD, Baxi S, Loviscach, et al. Regulation of glucose transport and insulin signaling by troglitazone or metformin in adipose tissue of type 2 diabetic subjects. Diabetes 2002; 51:30-36.

12. Freemark M, Bursey D. The effects of metforminon body mass index and glucose tolerance in obese adolescents with fasting hyperinsulinemia and a family history of type 2 diabetes. Pediatrics 2005; 107:55.

13. Magni P, Liuzzi A, Rusciea M, dozio E, ferrario S Bussi I. Free and bound plasma leptin in normal weight and obese men and women: relationship with body composition, resting energy expenditure insulin-sensitivity, lipid profile and macronutrient preference. Clin Endocrinol 2005; 62:189-196.

14. Yannakoulia M, Yiannakouris N, Bluher S, Mataas AL, Klimis Zacas Ezoros CS.  Soluble leptin deceptor, free leptin index, adiponectin and resisting concentration in healthy humans. J Clinic Endocrinol Metabol 2003; 88:1730-1736

15. Levri KM, MPH, Slaymaker E, Last A, Yeh J, Ference J, Amico FD, et al. Metformin as Treatment for Overweight and Obese Adults: A Systematic Review Ann Fam Med 2005:3; 457-46.

16. Yael Sandowski, Nina Raver, Eugene E. Gussakovsky Suzan Shochat Orly DymOded Livnah Menachem Rubinstein, Radha Krishna, and Arieh Gertler. Subcloning, Expression, Purification, and Characterization of Recombinant Human Leptin-binding Domain. J Biol Chem 2002; 277:46304-46309.

18.  Lupi R, Marchetti P,  Maffei M,  Del Guerra S,  Benzi L,  Marselli L, et al.  Effects of acute or prolonged exposure to human leptin on isolated human islet function. Bioch. Biophys. Res Commun. 1999; 256:637-641.

19. Kieffer TJ, Heller RS, Habener JF. Leptin receptors expressed on pancreatic cells. Bioch. Biophys Res Commun 1996; 22:522-527.  

20. Kuch B. Indexation of left ventricular mass in adults with a novel approximation for fat-free mass. J  Hyperten. 2000; 19:135-142.

21 Kay JP, Alemzadeh R, Langley G. Beneficial effect of Metformin in normoglycemicmorbidly obese adolescents. Metabol 2001; 50:1457-1461.

22.          Fruehwald-Schultes B, Oltmanns KM, Toschek B, Sopke S, Kern W, Born J.

 Short-term treatment with metformin decreases serum leptin concentration without affecting body weight and body fat content in normal-weight healthy men. Metabol 2002; 51:531-536.

23. Johannes K, Westphal, Daniel K, Britta M, Nina P, Volker Ot, et al. Metformin inhibits leptin secretion via a mitogen-activated protein kinase signalling pathway in brown adipocytes. J Endocrinol 2004; 183:299-307.

24. Michael, Jeffrey F, Horowitz, Simon WP. Effect of short term fasting on free and bound leptin concentration in lean and obese women. J Clin Endocrinol 2004; 86:3768-3771.

25. Ennis M, Fantus IG, Pritchard KI, Trudeau ME, Koo J, Hood N. Is leptin a mediator of adverse prognostic effects of obesity in breast cancer J Clin Oncol 2005; 23:6037-6042.

26. Shetty GK, Economides PA, Horton ES, Mantzoros CS, Veves A. Circulating adiponectin and resistin levels in relation to metabolic factors, inflammatory markers, and vascular reactivity in diabetic patients and subjects at risk for diabetes. Diabetes Car 2004; 27:2450-2457.