Tip 2 Diyabetli Hastalarda Serum Resistin Düzeyleri İle Obezite ve İnsülin Direnci Arasındaki İlişki

Öz

 Amaç: Tip 2 diyabetes mellitus (DM) hedef dokunun insüline dirençli olması ile karakterize olup obezite ile yakın ilişkilidir. Resistin yağ dokusundan türeyen bir hormon olup Tip 2 DM, obezite, insülin direnci ve inflamasyonla ilişkilendirilmektedir. Bu çalışmamızın amacı Tip 2 DM , bozulmuş glukoz toleransı olan (IGT) ve normal glukoz toleransı (NGT) olan gruplar arasındaki serum resistin seviyelerini karşılaştırmak ve bu seviyelerin obezite ve insülin direnciyle ilişkisini araştırmaktır.

Mateyal ve Metod:  Çalışma gruplarımız  toplam 72 kişiden oluşmaktadır. Serum resistin konsantrasyonlarını NGT(n=25), IGT(n=23) ve Tip 2 DM’lu grupların(n=24) glukoz, insülin, HbA1c, BMI, HOMA ve bel/kalça oranı ile karşılaştırdık. Daha sonra 72 vaka beden kütle indeksine(BMI) ve HOMA-IR  skoruna göre alt gruplara bölündü; obez olmayan BMI<25 kg/²(43 vaka), obez BMI>25kg/²(29 vaka), HOMA-IR(+)(23 vaka) ve HOMA-IR(-)(49 vaka). Açlık serum resistin seviyesi ELISA yöntemi ile ölçüldü. İnsülin direnci HOMA-IR formülüne göre hesaplandı. 

Bulgular: NGT, IGT ve Tip 2 DM grupları arasında serum resistin seviyeleri bakımından istatistiksel anlamlı farklılık yoktu(p>0,05). Obez olmayan gruba göre obez grupta daha yüksek serum resistin seviyeleri görüldü(p<0,01). HOMA skoru NGT grubuna göre IGT ve Tip 2 DM gruplarında daha yüksek bulundu(p<0,01). HOMA-IR(-) grup ve HOMA-IR(+) grupları arasında resistin seviyeleri bakımından istatistiksel anlamlı fark gözlenmedi(p>0,05). NGT grubunda resistin ile bel/kalça oranı arasında , IGT grubunda serum resistini ile açlık kan glukozu, sistolik kan basıncı, yaş arasında negatif korelasyon bulundu. (Sırasıyla; r=-0,45,p<0,05; r=-0,59,p<0,05; r=-0,53,p<0,01; r=0,46; r=0,45, p<0,05).

Sonuç: Resistinin glukoz metabolizmasını etkileyebileceğini, obezite ile ilişkili olabileceğini ancak insülin direnci ve diyabeti dolaylı yollardan etkileyebileceğini düşünmekteyiz. 

Anahtar Kelimeler:  Diyabetes Mellitus, HOMA, obezite, resistin

Aim: Type 2 diabetes mellitus (DM) characterized by target-tissue resistance to insülin and it is strongly linked to obesity. The adipocytes derived hormone resistin is involved in tip 2 DM, obesity, insülin resistance and iflammation. The aim of this study is to compare serum resistin levels between in normal glucose tolerance group (NGT), impaired glucose tolerance group (IGT) and Type 2 DM group and investigate correlations with obesity and insulin resistance.

Materials ve Methods: Firstly, we compared serum concentrations of resistin with glucose,insülin,HbA1C, BMI,HOMA and waist-to-hip ratio in subject with NGT(n=25), IGT(n=23) and type 2 DM(n=24).Later, according to the body mass index(BMI) and homeostasis model assesment of insulin resistance(HOMA-IR) score 72 cases were divided into subgroups; nonobese with BMI<25 kg/²(43 cases), the obese with BMI>25kg/²(29 cases), HOMA-IR(+)(23 cases) and HOMA-IR(-)(49 cases). Fasting serum resistin level was measured by ELISA. Insulin resistance was measured by the(HOMA-IR) formula.

Results: There was no statisfically difference in resistin levels between NGT, IGT and Type 2 DM gorups(p>0,05). Compared with non obese group, obese group showed higher serum resistin levels(p<0,01). HOMA score was found significantly higher in the IGT and Type 2 DM groups than NGT group(p<0,01). Between HOMA-IR(-) group and HOMA-IR(+) group no significant difference was observed between in the levels of resistin(p>0,05). A significant negative correlation observed between resistin and blood glucose waist-to-hip ratio (r=0,45,p<0,05) in NGT group, between resistin and fasting blood glucose, systolic blood pressure, age in IGT group (respectively;r=-0,45,p<05;r=-0,59,p<05;r=-0,53,p<0,01;r=0,46;r=0,45,p<0,05). 

Conclusion: We concluded that resistin may effect glucose metabolism, linked with obesity but indirectly effect insülin resistance and diabetes.

Key Words: Diabetes Mellitus, HOMA, obesity, resistin

Anahtar Kelimeler

• Diyabetes Mellitus,HOMA,obezite,resistin

References

1. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diabetes Care. 2009 January; 32(Supplement 1). .
2. Gerich JE. The genetic basis of type 2 diabetes mellitus: impaired insulin secretion versus impaired insulin sensitivity. Endocr. Rev. 1998 Aug;19(4):491-503.
3. Kahn BB, Flier JS. Obesity and insulin resistance. J Clin Invest. 2000 Aug;106(4):473-81. .
4. Jung RT. Obesity and nutritional factors in the pathogenesis of non-insülin dependent diabetes mellitus. In: Textbook of diabetes. Volume 1. Second Edition. Pickup JC, Williams G, eds. Oxford: Blackwell Science Ltd. 19. 1-19. 23, 1997. .
5. Boden G, Shulman GI. Free fatty acids in obesity and type 2 diabetes: defining their role in the development of insulin resistance and beta-cell dysfunction. Eur J Clin Invest. 2002 Jun;32 Suppl 3:14-23. .
6. Patel L, Buckels AC, Kinghorn IJ, et al. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 2003; 300: 472-6. .
7. Rajala MW, Obici S, Scherer PE & Rossetti L. Adipose-derived resistin and gut-derived resistin-like molecule-beta selectively impair insulin action on glucose production. Journal of Clinical Investigation 2003; 111: 225–230. .
8. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS & Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307–312. .

9. American Diabetes Association. Diagnosis and classification of diabetes mellitus. Diab Care 2010; 33: P62–69. .
10. Steppan CM & Lazar MA. Resistin and obesity-associated insulin resistance. Trends in Endocrinology and Metabolism 2002; 13: 18-23. .
11. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS & Lazar MA. The hormone resistin links obesity to diabetes. Nature 2001; 409: 307–312. .
12. Zhong Q, Lin CY, Clarke KJ, Kemppainen RJ, Schwartz DD, Judd RL. Endothelin-1 inhibits resistin secretion in 3T3-L1 adipocytes. Biochem Biophys Res Commun. 2002; 296: 383-387. .
13. Coello SD, Cabrera de LD, Almeida GA, Gonza´lez A. et al. association between serum resistin and insulin resistance in humans. Diabetes research and clinical practice 2008; 82: 256 – 261. .
14. Sentinelli F, Romeo S, Arca M, Filippi E, Leonetti F, Banchieri M, Di Mario U, Baroni MG. Human resistin gene, obesity, and type 2 diabetes: mutation analysis and population study. Diabetes 2002. 51: 860-862. .
15. Daghri NA, Chetty R, McTernan PG, Rubean KA, Attas OA, Jones AF and S Kumar. Serum resistin is associated with C-reactive protein and LDL cholesterol in type 2 diabetes and coronary artery disease in a Saudi population.. Cardiovascular Diabetology 2005; 4: 10.. .
16. McTernan PG, Fisher FM, Valsamakis G. et al. Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes.. J. Clin. Endocrinol. Metab. 2003; 88: 6098–6106. .
17. Fujinami A, Obayashi H, Ohta K. et al. Enzyme-linke immunosorbent assay for circulating human resistin: resistin concentrations in normal subjects and patients with type 2 diabetes. Clin. Chim. Acta. 2004; 339, 57–63.. .
18. Youn BS, Kang-Yeol Yu KY, Park HJ, Lee NS, Min SS, Youn MY, at all. Plasma Resistin Concenratipns Measured by Enzyme Linked Immunosorbent Assay Using a Newly Developed Monoclonal Antibody Are Elevated in Individuals with Type 2 Diabetes Mellitus. The Journal of Clinical Endokrinology and Metabolism 2004; 89, 150-156. .
19. Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, et al. Serum resistin (FIZZ3) protein is increased in obese humans. J. Clin. Endocrinol. Metab. 2003; 88: 5452–5455. .
20. Vendrell J, Broch M, Vilarrasa N, Molina A, Gomez JM, Gutierrez C, Simon I, Soler J, Richart C. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes Res. 2004; 12 (6) : 962-71. .
21. Schaffler A, Buchler C, Muller-Ladner U. Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus. Horm. Metab. Res. 2004; 36: 702–707. .
22. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal- Puig A, Considine RV, O’Rahilly S. Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-g action in humans. Diabetes 2001; 50: 2199-2202. .
23. Azuma K, Katsukawa F, Oguchi, et al. Correlation between serum resistin level and adiposity in obese individuals. Obes. Res. 2003; 11: 997–1001. .
24. Yannakoulia M, Yiannakouris N, Bluher S, Matalas AL, Klimis-Zacas D, Mantzoros CS. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab. 2003; 88: 1730–6. .
25. Vozarova de CB, Degawa-Yamauchi M, Considine RV, Tataranni PA and Volarova de CB. High serum resistin is associated with an increase in adiposity but not a worsening of insulin resistance in Pima Indians. Diabetes 2004; 53: 1279–1284. .
26. Nagaev I, Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun. 2001; 285: 561–564. .
27. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal- Puig A, Considine RV, O’Rahilly S. Resistin / Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-g action in humans. Diabetes 2001; 50: 2199-2202. .
28. Osawa H, Yamada K, Onuma H, et al. The G/G genotype of a resistin single-nucleotide polymorphism at 420 increases type 2 diabetes Metabolism Clinical and Experimental 56 (2007) 693–698. .
29. McTernan PG, McTernan CL, Chetty R, et al. Increased resistin gene and protein expression in human abdominal adipose tissue J. Clin. Endocrinol. Metab. 2002; 87, 2407. .
30. Smith SR, Bai F, Charbonneau C, Janderova L, Argyropoulos G. A promoter genotype and oxidative stress potentially link resistin to human insulin resistance. Diabetes 2003; 52: 1611–1618. .
31. Silha JV, Krsek M, Skrha JV, et al. Plasma resistin, adiponectin and leptin levels in lean and obese subjects: correlations with insulin resistance. Eur J Endocrinol 2003; 149: 331-5. .
32. Tokuyamaa Y, Osawab H, Ishizukaa T, Onumab H, Matsuic K, Egashirac T, Makinob H, Kanatsukaa A. Serum resistin level is associated with insulin sensitivity in Japanese patients with type 2 diabetes mellitus. Metabolism Clinical and Experimental 2007; 56: 693– 698. .
33. Hui-Ling Lu, Hong-Wei Wang, Yu Wen, Mu-Xun Zhang, Han-Hua Lin. Roles of adipocyte derived hormone adiponectin and resistinin insulin resistance of type 2 diabetes. World J Gastroenterol 2006; 21; 12(11): 1747-1751. .
34. Utzschneider KM, Carr DB, Tong J, et al. Resistin is not associated with insulin sensitivity or the metabolic syndrome in humans. Diabetologia 2005; 48: 2330- 3. .
35. Janke J, Engeli S, Gorzelniak K, et al. Resistin gene expression in human adipocytes is not related to insulin resistance. Obes Res. 2002; 10: 1–5. .
36. Lee JH, Chan JL, Yiannakouris N, et al. Circulating resistin levels are not associated with obesity or insulin resistance in humans and are not regulated by fasting or leptin administration: cross-sectional and interventional studies in normal, insulin-resistant, and diabetic subjects. J Clin Endocrinol Metab. 2003; 88: 4848 –56. .
37. Janowska J, Markiewicz BZ, Glinianowicz MO. Relationship between serum resistin concentration and proinflammatory cytokines in obese women with impaired and normal glucose tolerance Metabolism Clinical and Experimental 2006; 55,1495-1499. .
38. Osawa H, Onuma H, Ochi M, et al. Resistin SNP-420 determines its monocyte mRNA and serum levels inducing type 2 diabetes. Biochem Biophys Res Commun 2005; 335: 596- 602. .