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Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon ve İnsülin Direnci ile İlişkisi

Yıl 2022, Cilt: 3 Sayı: 2, 184 - 197, 01.08.2022

Öz

Giriş: Glikoz intoleransının erken dönem karaciğer hastalığının siroza ilerlemesinde önemli bir rol oynadığı gösterilmiştir. Kronik karaciğer hastalarındaki glikoz intoleransından insülin direncinin sorumlu olduğu öne sürülmektedir. Kronik karaciğer hastalığında kronik inflamasyon aracılığıyla artan resistinin insülin direncinden sorumlu olabileceği düşünülmektedir. Çalışmamızda siroz hastalığı olanlarda adipoz dokudan salınan resistinin, insülin direnci, inflamasyon belirteçleri ve hastalık evresi ile ilişkisini değerlendirilmeyi amaçladık. Yöntemler: Eskişehir Osmangazi Üniversitesi Tıp Fakültesi Gastroenteroloji Bilim Dalı’nda Mart 2008 – Temmuz 2009 tarihleri arasında siroz tanısı alan 46 hasta ve kontrol grubu olarak 19 sağlıklı birey çalışmaya dahil edildi. Diabetes Mellitus, diğer endokrin hastalık veya Hepatocellüler Karsinoma tanılı, açlık kan glikozu 126 mg/dl nin üzerinde olan ve glikoz metabolizması üzerine etki edebilecek ilaç kullanan hastalar çalışma dışı bırakıldı. Deri kıvrım kalınlığı (biseps, triseps, suprailiyak ve subskapular) ölçümü yöntemiyle obezitesi olan katılımcılar belirlendi. Çalışma ve kontrol gruplarından obez hastalar dışlanarak istatistik incelemeler yapıldı. Serum resistin düzeyi tespitinde AssayMax Human Resistin ELISA Kiti kullanıldı. İnsülin direncini saptamak amacıyla “İnsülin Direnci için Homeostatik Model” (HOMA-IR) formülü kullanıldı. Çalışılan parametreler çalışma ve kontrol grupları arasında ayrıca çalışma grubunda hastalık evresine göre oluşturulan üç grup arasında (Child Pugh evre A, B ve C) istatistiksel olarak karşılaştırıldı. Bulgular: İnsülin direncini yansıtan tüm laboratuvar parametreleri, inflamasyon belirteçleri ve resistin düzeylerinin çalışma grubunda anlamlı ölçüde yüksek olduğu saptanmıştır. Hastalık şiddet ve prognozunu belirlemede kullanılan Child Pugh evresi ilerledikçe resistin seviyelerinde artış olduğu ancak total yağ oranında azalmayla birlikte insülin direncine sahip hasta oranının da azaldığı gözlenmiştir. Resistinin açlık insülin düzeyi dışında insülin direncinin diğer belirteçleriyle arasında anlamlı bir ilişki saptanmamıştır. Sonuç: Sirozlu hastalarda yapılacak metabolizma çalışmalarında vücut yağ oranının saptanmasında deri kıvrım kalınlığı tespiti faydalı olabilir. Siroz hastalarında insülin direnci belirteçleri anlamlı derecede yüksektir ve resistin düzeyleri hastalık şiddeti arttıkça artış gösterir. Siroz hastalarında değişik mekanizmalarla ortaya çıkan insülin direnci gelişiminde resistinin katkısının olmadığı görüşündeyiz.

Destekleyen Kurum

Yoktur

Proje Numarası

Yoktur

Teşekkür

Çalışmamız için çalışma grubu hastalarının belirlenmesi aşamasındaki destekleri için Doç. Dr. Tuncer TEMEL'e ve istatistik analizlerin yapılmasındaki katkıları için Öğretim Görevlisi Ahmet MUSMUL’a teşekkür ederiz.

Kaynakça

  • Petrides AS, Vogt C, Schulze-Berge D, Matthews D, Strohmeyer G. Pathogenesis of Glucose Intolerance and Diabetes Mellitus in Cirrhosis. Hepatology 1994;19(3):616-27.
  • Bianchi G, Wchesini G, Zoli M, Bugianesi E, Fabbri A, Pisi E. Prognostic Significance of Diabetes in Patients with Cirrhosis. Hepatology 1994;20(1):119-24.
  • Fartoux L, Poujol-Robert A, Guéchot J, Wendum D, Poupon R, Serfaty L. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut 2005;54:1003–8.
  • Paschke R, Fasshauer M. Regulation of adipocytokines and insulin resistance. Diabetologia 2003;46: 1594–603.
  • Yagmur E, Trautwein C, Gressner AM, Tacke F. Resistin serum levels are associated with insulin resistance, disease severity, clinical complications, and prognosis in patients with chronic liver diseases. Am J Gastroenterol 2006;101(6):1244–52.
  • Kakizaki S, Sohara N, Yamazaki Y et al. Elevated plasma resistin concentrations in patients with liver cirrhosis. J Gastroenterol Hepatol 2008;23(1):73–7.
  • Bahr MJ, Ockenga J, Boker KHW, Manns MP, Tietge UJF. Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance. Am J Physiol Endocrinol Metab 2006;291(2):199–206.
  • Eldib AE, Makboul KM, Mahdy MM, Zaky DZ, Seddik ME. Resistin Hormone A Possible Marker of Insulin resistance in chronic HCV and Type 2 Diabetic patients. jabs.fums.ac.ir 2018;11(12):1097–8135.
  • Isaac A, Hamdy Abd El-Mageed K, Haroun Kaisar H et al. Assessment of serum Resistin in detecting Insulin Resistance and their impact on response to direct acting antiviral in chronic viral hepatitis C patients. Egypt Liver J 2021; 11(1): 1-9.
  • Elsayed EY, Mosalam NA, Mohamed NR. Resistin and Insulin Resistance: A Link Between Inflammation and Hepatocarcinogenesis. Asian Pac J Cancer Prev 2015;16(16):7139–42.
  • Durnin JVGA, Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 Years. Br J Nutr 1974;32(1):77–97.
  • Jackson AS, Pollock ML. Generalized equations for predicting body density of men. Br J Nufr 1978;40: 497-507.
  • Bray GA, Greenway FL, Molitch ME, Dahms WT, Atkinson RL, Hamilton K. Use of anthropometric measures to assess weight loss. Am J Clin Nutr 1978;31(5):769–73.
  • Siri WE, Brozek J and Henschel A. Techniques for Measuring Body Compositions, Natl Acad Sci 1961; 223-224.
  • The American Council on Exercise. Body fat percentages. Available at: http://en.wikipedia.org/wiki/Body fat percentage. Accessed November 06,2009.
  • Matthews DR, Hosker JR, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28(7):412-9.
  • Katz A, Nambi SS, Mather K, et al. Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans. J Clin Endocrinol Metab 2000; 85(7): 2402-10.
  • Weidmann P, Uehlinger DE, Gerber A. Antihypertensive treatment and serum lipoproteins. J Hypertens 1985; 3(4): 297-306.
  • Müller MJ, Böker KHW, Selberg O. Metabolism of energy-yielding substrates in patients with liver cirrhosis. Clin Investig 1994;72(8):568–79.
  • Wong F, Logan A, Blendis L. Hyperinsulinemia in preascitic cirrhosis: Effects on systemic and renal hemodynamics, sodium homeostasis, forearm blood flow, and sympathetic nervous activity. Hepatology 1996;23(3):414–22.
  • Cavallo-Perin P, Cassader M, Bozzo C, et al. Mechanism of Insulin Resistance in Human Liver Cirrhosis Evidence of a Combined Receptor and Postreceptor Defect. J Clin Invest 1985;75(5):1659-65.
  • Merli M, Leonetti F, Riggio O, et al. Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation. Hepatology 1999;30(3): 649–54.
  • Cousin B, Munoz O, Andre M, et al. A role for preadipocytes as macrophage-like cells. FASEB J 1999; 13(2):305-12.
  • Periyalwar P and Srinivasan D. Malnutrition in cirrhosis: contribution and consequences of sarcopenia on metabolic and clinical responses. Clin Liver Dis 2012;16(1):95-131.
  • Saltiel AR, and Kahn R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature (13 December) 2001; 414(6865): 799-806.
  • Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 2002;13(1):18-23.
  • Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature 2001;409(6818):307–12.
  • Mariadi K, Koncoro H, Wibawa IDN. C-Reactive Protein and Interleukin-6 Correlated with Resistin Level in Liver Cirrhosis. The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy 2020;21(1):17-21.
  • 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.
  • Custovic N, Rasic S. Relationship Of Serum Adiponectin And Resistin Levels With Theseverity Of Liver Fibrosis In Patients With Chronic Hepatitis B. J Med Biochem 2022; 41: 1 –9.
  • Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89(6):2548-56.
  • Wasim H, Al-Daghri NM, Chetty R, Mcternan PG, Barnett AH, Kumar S. Cardiovascular Diabetology Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians. Cardiovasc Diabetol 2006;5(10): 1-5.
  • Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 2006;74: 443-77.
  • Chandalia M, Abate N. Metabolic complications of obesity: inflated or inflamed? Journal of Diabetes and its Complications. J Diabetes Complications 2007;21(2):128-36.
  • Eldib A, Makboul K, Mahdy M, Zaky D, Seddik ME. Resistin Hormone A Possible Marker of Insulin resistance in chronic HCV and Type 2 Diabetic patients. Life Sci J 2014;11(12): 78-84.

The Relationship of Resistin with Disease Severity, Inflammation and Insulin Resistance in Cirrhosis Patients

Yıl 2022, Cilt: 3 Sayı: 2, 184 - 197, 01.08.2022

Öz

Introduction: Glucose intolerance has been shown to play an important role in the progression of early liver disease to cirrhosis. It has been suggested that insulin resistance is responsible for glucose intolerance in patients with chronic liver disease. It is thought that increased resistin through chronic inflammation in chronic liver disease may be responsible for insulin resistance. In our study, we aimed to evaluate the relationship of resistin which is released from adipose tissue with insulin resistance, inflammation markers and disease stage in patients with cirrhosis. Methods: Forty-six patients diagnosed with cirrhosis in Eskişehir Osmangazi University Faculty of Medicine, Department of Gastroenterology between March 2008 and July 2009, and 19 healthy individuals as a control group were included in the study. Patients with a diagnosis of Diabetes Mellitus, other endocrine disease or Hepatocellular Carcinoma, with fasting blood glucose above 126 mg/dl and using drugs that may affect glucose metabolism were excluded from the study. Participants with obesity were determined by skinfold thickness (biceps, triceps, suprailiac and subscapular) measurement. Statistical analyzes were performed by excluding obese patients from the study and control groups. AssayMax Human Resistin ELISA Kit was used to determine serum resistin level. The "Homaostatic Model for Insulin Resistance" (HOMA-IR) formula was used to detect insulin resistance. The studied parameters were statistically compared between the study and control groups and also between the three groups (Child Pugh stage A, B and C) formed according to the disease stage in the study group. Results: All laboratory parameters reflecting insulin resistance, inflammation markers and resistin levels were found to be significantly higher in the study group. As the Child Pugh stage advances, which is used to determine the severity and prognosis of the disease, resistin levels found higher, but it was observed that the rate of patients with decreased insulin resistance had lower levels in total fat ratio. No significant correlation was found between resistin and other markers of insulin resistance except fasting insulin level. Conclusion: In the future metabolism studies which to be performed in patients with cirrhosis detection of skinfold thickness may be useful in determining body fat ratio. Insulin resistance markers are significantly higher in patients with cirrhosis, as disease severity advances resistin levels increases. We are in the opinion that resistin does not contribute to the development of insulin resistance, which occurs with different mechanisms in patients with cirrhosis.

Proje Numarası

Yoktur

Kaynakça

  • Petrides AS, Vogt C, Schulze-Berge D, Matthews D, Strohmeyer G. Pathogenesis of Glucose Intolerance and Diabetes Mellitus in Cirrhosis. Hepatology 1994;19(3):616-27.
  • Bianchi G, Wchesini G, Zoli M, Bugianesi E, Fabbri A, Pisi E. Prognostic Significance of Diabetes in Patients with Cirrhosis. Hepatology 1994;20(1):119-24.
  • Fartoux L, Poujol-Robert A, Guéchot J, Wendum D, Poupon R, Serfaty L. Insulin resistance is a cause of steatosis and fibrosis progression in chronic hepatitis C. Gut 2005;54:1003–8.
  • Paschke R, Fasshauer M. Regulation of adipocytokines and insulin resistance. Diabetologia 2003;46: 1594–603.
  • Yagmur E, Trautwein C, Gressner AM, Tacke F. Resistin serum levels are associated with insulin resistance, disease severity, clinical complications, and prognosis in patients with chronic liver diseases. Am J Gastroenterol 2006;101(6):1244–52.
  • Kakizaki S, Sohara N, Yamazaki Y et al. Elevated plasma resistin concentrations in patients with liver cirrhosis. J Gastroenterol Hepatol 2008;23(1):73–7.
  • Bahr MJ, Ockenga J, Boker KHW, Manns MP, Tietge UJF. Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance. Am J Physiol Endocrinol Metab 2006;291(2):199–206.
  • Eldib AE, Makboul KM, Mahdy MM, Zaky DZ, Seddik ME. Resistin Hormone A Possible Marker of Insulin resistance in chronic HCV and Type 2 Diabetic patients. jabs.fums.ac.ir 2018;11(12):1097–8135.
  • Isaac A, Hamdy Abd El-Mageed K, Haroun Kaisar H et al. Assessment of serum Resistin in detecting Insulin Resistance and their impact on response to direct acting antiviral in chronic viral hepatitis C patients. Egypt Liver J 2021; 11(1): 1-9.
  • Elsayed EY, Mosalam NA, Mohamed NR. Resistin and Insulin Resistance: A Link Between Inflammation and Hepatocarcinogenesis. Asian Pac J Cancer Prev 2015;16(16):7139–42.
  • Durnin JVGA, Womersley J. Body fat assessed from total body density and its estimation from skinfold thickness: measurements on 481 men and women aged from 16 to 72 Years. Br J Nutr 1974;32(1):77–97.
  • Jackson AS, Pollock ML. Generalized equations for predicting body density of men. Br J Nufr 1978;40: 497-507.
  • Bray GA, Greenway FL, Molitch ME, Dahms WT, Atkinson RL, Hamilton K. Use of anthropometric measures to assess weight loss. Am J Clin Nutr 1978;31(5):769–73.
  • Siri WE, Brozek J and Henschel A. Techniques for Measuring Body Compositions, Natl Acad Sci 1961; 223-224.
  • The American Council on Exercise. Body fat percentages. Available at: http://en.wikipedia.org/wiki/Body fat percentage. Accessed November 06,2009.
  • Matthews DR, Hosker JR, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28(7):412-9.
  • Katz A, Nambi SS, Mather K, et al. Quantitative Insulin Sensitivity Check Index: A Simple, Accurate Method for Assessing Insulin Sensitivity In Humans. J Clin Endocrinol Metab 2000; 85(7): 2402-10.
  • Weidmann P, Uehlinger DE, Gerber A. Antihypertensive treatment and serum lipoproteins. J Hypertens 1985; 3(4): 297-306.
  • Müller MJ, Böker KHW, Selberg O. Metabolism of energy-yielding substrates in patients with liver cirrhosis. Clin Investig 1994;72(8):568–79.
  • Wong F, Logan A, Blendis L. Hyperinsulinemia in preascitic cirrhosis: Effects on systemic and renal hemodynamics, sodium homeostasis, forearm blood flow, and sympathetic nervous activity. Hepatology 1996;23(3):414–22.
  • Cavallo-Perin P, Cassader M, Bozzo C, et al. Mechanism of Insulin Resistance in Human Liver Cirrhosis Evidence of a Combined Receptor and Postreceptor Defect. J Clin Invest 1985;75(5):1659-65.
  • Merli M, Leonetti F, Riggio O, et al. Glucose intolerance and insulin resistance in cirrhosis are normalized after liver transplantation. Hepatology 1999;30(3): 649–54.
  • Cousin B, Munoz O, Andre M, et al. A role for preadipocytes as macrophage-like cells. FASEB J 1999; 13(2):305-12.
  • Periyalwar P and Srinivasan D. Malnutrition in cirrhosis: contribution and consequences of sarcopenia on metabolic and clinical responses. Clin Liver Dis 2012;16(1):95-131.
  • Saltiel AR, and Kahn R. Insulin signalling and the regulation of glucose and lipid metabolism. Nature (13 December) 2001; 414(6865): 799-806.
  • Steppan CM, Lazar MA. Resistin and obesity-associated insulin resistance. Trends Endocrinol Metab 2002;13(1):18-23.
  • Steppan CM, Bailey ST, Bhat S, et al. The hormone resistin links obesity to diabetes. Nature 2001;409(6818):307–12.
  • Mariadi K, Koncoro H, Wibawa IDN. C-Reactive Protein and Interleukin-6 Correlated with Resistin Level in Liver Cirrhosis. The Indonesian Journal of Gastroenterology, Hepatology, and Digestive Endoscopy 2020;21(1):17-21.
  • 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.
  • Custovic N, Rasic S. Relationship Of Serum Adiponectin And Resistin Levels With Theseverity Of Liver Fibrosis In Patients With Chronic Hepatitis B. J Med Biochem 2022; 41: 1 –9.
  • Kershaw EE, Flier JS. Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004;89(6):2548-56.
  • Wasim H, Al-Daghri NM, Chetty R, Mcternan PG, Barnett AH, Kumar S. Cardiovascular Diabetology Relationship of serum adiponectin and resistin to glucose intolerance and fat topography in south-Asians. Cardiovasc Diabetol 2006;5(10): 1-5.
  • Fain JN. Release of interleukins and other inflammatory cytokines by human adipose tissue is enhanced in obesity and primarily due to the nonfat cells. Vitam Horm 2006;74: 443-77.
  • Chandalia M, Abate N. Metabolic complications of obesity: inflated or inflamed? Journal of Diabetes and its Complications. J Diabetes Complications 2007;21(2):128-36.
  • Eldib A, Makboul K, Mahdy M, Zaky D, Seddik ME. Resistin Hormone A Possible Marker of Insulin resistance in chronic HCV and Type 2 Diabetic patients. Life Sci J 2014;11(12): 78-84.
Toplam 35 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Konular Sağlık Kurumları Yönetimi
Bölüm Araştırma Makaleleri
Yazarlar

Serdar Efe 0000-0002-1229-0602

Ayşegül Özakyol 0000-0003-0152-8651

Proje Numarası Yoktur
Yayımlanma Tarihi 1 Ağustos 2022
Yayımlandığı Sayı Yıl 2022 Cilt: 3 Sayı: 2

Kaynak Göster

APA Efe, S., & Özakyol, A. (2022). Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon ve İnsülin Direnci ile İlişkisi. Eskisehir Medical Journal, 3(2), 184-197.
AMA Efe S, Özakyol A. Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon ve İnsülin Direnci ile İlişkisi. Eskisehir Med J. Ağustos 2022;3(2):184-197.
Chicago Efe, Serdar, ve Ayşegül Özakyol. “Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon Ve İnsülin Direnci Ile İlişkisi”. Eskisehir Medical Journal 3, sy. 2 (Ağustos 2022): 184-97.
EndNote Efe S, Özakyol A (01 Ağustos 2022) Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon ve İnsülin Direnci ile İlişkisi. Eskisehir Medical Journal 3 2 184–197.
IEEE S. Efe ve A. Özakyol, “Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon ve İnsülin Direnci ile İlişkisi”, Eskisehir Med J, c. 3, sy. 2, ss. 184–197, 2022.
ISNAD Efe, Serdar - Özakyol, Ayşegül. “Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon Ve İnsülin Direnci Ile İlişkisi”. Eskisehir Medical Journal 3/2 (Ağustos 2022), 184-197.
JAMA Efe S, Özakyol A. Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon ve İnsülin Direnci ile İlişkisi. Eskisehir Med J. 2022;3:184–197.
MLA Efe, Serdar ve Ayşegül Özakyol. “Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon Ve İnsülin Direnci Ile İlişkisi”. Eskisehir Medical Journal, c. 3, sy. 2, 2022, ss. 184-97.
Vancouver Efe S, Özakyol A. Siroz Hastalarında Resistinin Hastalık Şiddeti, İnflamasyon ve İnsülin Direnci ile İlişkisi. Eskisehir Med J. 2022;3(2):184-97.