Effect of Diabetes Mellitus on the Excretory Function of the Liver
DOI:
https://doi.org/10.31964/mltj.v0i0.416Keywords:
Diabetes mellitus, liver enzymes, hepatic injury.Abstract
Diabetes mellitus is an internationally recognized health problem and a leading cause of death worldwide. However, the most significant increase in prevalence is expected to occur in Asia and Africa, where most patients will be found by 2030. Diabetic Mellitus is a clinical and metabolic syndrome characterized by abnormal carbohydrate, protein, and fat metabolism resulting in hyperglycemia, increased protein breakdown, Ketosis or acidosis due to absolute or relative deficiency, and insulin resistance, thereby leading to vascular complications such as retinopathy, neuropathy, and nephropathy. This study evaluated the levels of plasma bilirubin, ALP, and GGT among diabetic patients. A total of eighty (80) individuals were recruited for the study comprising of forty (40) diabetes patients with age range 25-80 years and forty (40) control subjects with the age range of 20-30 years in Irrua/Ekpoma, Edo State, Nigeria. The study was carried out within six months (December 2018 - May 2019). All patients were diabetes. The serum Alkaline Phosphatase (ALP), gamma-glutamyl transferase (GGT), total and conjugated bilirubin were assayed by spectrophotometric method, and the data obtained were statistically analyzed using SPSS version 23.0 software. Serum levels of ALP, GGT, Total and unconjugated bilirubin were significantly elevated (P<0.05) among diabetes patients than control subjects except for conjugated bilirubin which was lower (P>0.05) when compared with that of the control subjects. The mean serum levels of ALP, GGT, total, unconjugated and conjugated bilirubin of male diabetes patients were non statistically significant (P>0.05) when compared with female diabetes subjects except the age (P<0.05). These findings indicate that hepatic injury was more likely among diabetes, and liver enzymes (ALP, GGT) are critical for monitoring glucose control concomitant with hepatic injury. Bilirubin is a potentially important biomarker for the assessment of the hepatic excretory system in diabetes mellitus.References
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Al-Jameil, N., Khan, F. A., Arjumand, S., Khan, M.F. and Tabassum, H. (2014). Associated Liver Enzymes with Hyperlipidemic Profile in Type 2 Diabetes Patients. International Journal of Clinical and Experimental Pathology, 7, 4345-4349
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Bin Dahman, L. , Humam, M. , Barahim, O. , Barahman, O. & Balfas, M. (2021). Association between Liver Enzymes and Dyslipidemia in Yemeni Patients with Type Two Diabetes Mellitus. Journal of Diabetes Mellitus, 11, 41-51 doi: 10.4236/jdm.2021.112004.
Breimer, L.H. (1995). Serum bilirubin and risk of ischaemic heart disease in middle age British men. Clinical Chemistry, 41, 1504-1545.
Chen, Y.H., Chau, L.Y. & Chen, J.W. (2008). Serum bilirubin and ferritin level link haeme oxygenase 1 gene promoter polymorphism and susceptibility to coronary artery disease in diabetes patient. Diabetes care, 31(8),1615–1620
Falchuk. K.R. & Colin S. (1993). The intestinal and Liver complication of diabetes mellitus. Advance Internal Medicine, 38, 269-286
Gavin, N. and Levinthal, A.S.T. (1999). Liver Disease and Diabetes Mellitus. Clinical Diabetes, 17(2)
Giannini, E.G., Testa, R. and Savarino, V. (2005). Liver Enzyme Alteration: A Guide for Clinicians. Canadian Medical Association Journal, 172, 367-379. https://doi.org/10.1503/cmaj.1040752
Ginsberg, H.N.(1996). Diabetic dyslipidemia: basic mechanism underlying the common hypertriglyceridemia and low HDL cholesterol levels. Diabetes, 645(suppl 3), S27 –S30
Hammerman, C., Goldstein, R., Kaplan, M., Eran, M. & Goldschmide, D. (1998) . Bilirubin in the premature: toxic waste or natural defence? Clinical Chemistry, 44(12), 255-2553
Hanigan, M.H. & Frierson Jr., H.F.(1996), Immunohistochemical Detection of Gamma-Glutamyl Transpeptidase in Normal Human Tissue. Journal of Histochemistry & Cytochemistry,44, 1101-11108. https://doi.org/10.1177/44.10.8813074
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Hopkins, P.N., Wu, L.L., Hunt, S.G. & Jame B.G. (1996). Higher serum bilirubin is associated with decreased risk for early familiar coronary artery disease. Arteriosclerosis Thrombosis Vascular Biology, 16, 250-255.
Hsueh, W.A. & Quinones, M.J. (2003). Role of endothelial dysfunction in insulin resistance. American Journal Cardiology, 92,10–17
Inogochi, T., Sasaki, S., Kobayashi, K. & Takayanagi, R. (2007). Relationship between Gilbert syndrome and prevalence of vascular complications in patients with diabetes. JAMA, 298, 1398-1400
Kern, W.H., Herger, A. H., Payne, J. H. & Dewind, L.T. (1973). Fatty metamorphosis of liver in morbid obesity. Archives of Pathology and Laboratory Medicine, 96, 342–346
Lee, D. H., Ha, M. H., Kim, J. H. & Christiani, D. C. (2003). Gamma-glutamyl Transferases and diabetes: A 4 years follow up study. Diabetologia, 46, 359–364
Lee, D.H. & Jacobs Jr., D.R. (2004). Association between Serum Gamma-Glutamyl transferase and C-Reactive Protein. Atherosclerosis, 178, 327-330. https://doi.org/10.1016/j.atherosclerosis.2004.08.027
Lin, J.P., Donell, C.J., schwager, J.P. & Cupples, L.A. (2006). Association between the UGT1A1 28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart study. Circulation, 114(14), 1476-1481.
Malnick, S.D., Bzergabe., M. & Knobler, H. (2003). Non–alcoholic fatly liver: a common manifestation of a metabolic disorder. Quarterly Journal of Medicine, 96, 699–709
Marchesini, G., Brizi, M., Blanchi, G. & Tomassetti, S. (2001). Nonalcoholic fatty liver disease a feature of the metabolic syndrome. Diabetes, 50, 1844–1850
Martin, A.C. (2006). Cardrovascular risk factors. In a textbook of clinical chemistry and metabolic medicine (7th ed) publisher. Hodder Arnold. pp. 322
Monami,M., Barchini,G.,Lamma,K.& Pala, L. (2008). Liver enzymes and risks of diabetes and cardiovascular disease. Metabolism, 57(3), 387-392
Ndisang, J.F., Lane, N. and Jadhav A. (2009). Upregulation of the haeme oxygenase system ameliorates postprandial and fasting hyperglycaemia in type 2 diabetes. Ameican Journal of Physiology- Endocrinology and Metabolism, 296(3), E1029–104.
Perlstein, T.S., Pande, R.L., Beckman, J.A. & Creager, M.A. (2008). Serum total bilirubin level and prevalent lower – extremity peripheral arterial disease: National Health and Nutrition Examination Survey (NHANES) 1999 – 2004. Arteriosclerosis Thrombosis vascular Biology, 28(1), 166
Schielman, J.D., Goodman , S.I., Mace, J.W.& Patrick, A. (1975). Glutathionuria inborn error of metabolism due to tissue deficiency of gamma – glutamyl transpeptidase. Biochemical and Biophysical Research Communication, 65(1), 68–74. Doi:10.1016/S0006 – 291 (75) 80062
Schwertner, H.A., Jackson, W.G. & Tolan, G. (1994). Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clinical Chemistry, 40, 18-23.
Sherlock,S. (1985). Diseases of liver and biliary tract. Published by Blackwell Scientific Publication. Pp. 386-387
Stocker, R., Yamamoto, Y., McDonagh, A.F. & Glazer, A.N. (1987). Bilirubin is an antioxidant of possible physiological importance. Science, 235,1043-6
Turgut, O. & Tandogan, I. (2011). Gamma-Glutamyltransferase to determine Cardiovascular Risk: Shifting the Paradigm Forward. Journal of Atherosclerosis and Thrombosis, 18, 177-181
Wang, Y., Koh, W., Yuan, J. & Pan, A. (2016). Association between Liver Enzymes and Incident Type 2 Diabetes in Singapore Chinese Men and Women. British Medical Journal Open Diabetes Research and Care, 4, e000296. https://doi.org/10.1136/bmjdrc-2016-000296
Whitfield, J.B. (2001). Gamma–glutamyl transferase. Critical Review Clinical laboratory science, 38, 263–355
World Health Organization. (1999). Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Part 1, Diagnosis and Classification of Diabetes Mellitus. World Health Organization, Geneva, https://apps.who.int/iris/handle/10665/66040
Zimmerman, H. J., MacMurray, F. G., Rapaport, H. & Alpert, L. K. (1950). Studies of liver in diabetes mellitus. structural and functional abnormalities. Journal of Laboratory and clinical medicine, 36, 912–921
Ali, A.T., Penny, C.B. & Paiker, J.E. (2006). The effect of alkaline phosphatase inhibitor on intracellular lipid accumulation in preadipocyte isolated from human mammary tissues. Annal Clinical Biochemistry, 43, 207-213
Al-Jameil, N., Khan, F. A., Arjumand, S., Khan, M.F. and Tabassum, H. (2014). Associated Liver Enzymes with Hyperlipidemic Profile in Type 2 Diabetes Patients. International Journal of Clinical and Experimental Pathology, 7, 4345-4349
Ballestri, S., Zona, S., Targher, G., Romagnoli, D., Baldelli, E., Nascimbeni, F., et al.: (2016). Nonalcoholic Fatty Liver Disease Is Associated with an Almost Twofold Increased Risk of Incident Type 2 Diabetes and Metabolic Syndrome. Evidence from a Systematic Review and Meta-Analysis. Journal of Gastroenterology and Hepatology, 31, 936-944. https://doi.org/10.1111/jgh.13264
Bin Dahman, L. , Humam, M. , Barahim, O. , Barahman, O. & Balfas, M. (2021). Association between Liver Enzymes and Dyslipidemia in Yemeni Patients with Type Two Diabetes Mellitus. Journal of Diabetes Mellitus, 11, 41-51 doi: 10.4236/jdm.2021.112004.
Breimer, L.H. (1995). Serum bilirubin and risk of ischaemic heart disease in middle age British men. Clinical Chemistry, 41, 1504-1545.
Chen, Y.H., Chau, L.Y. & Chen, J.W. (2008). Serum bilirubin and ferritin level link haeme oxygenase 1 gene promoter polymorphism and susceptibility to coronary artery disease in diabetes patient. Diabetes care, 31(8),1615–1620
Falchuk. K.R. & Colin S. (1993). The intestinal and Liver complication of diabetes mellitus. Advance Internal Medicine, 38, 269-286
Gavin, N. and Levinthal, A.S.T. (1999). Liver Disease and Diabetes Mellitus. Clinical Diabetes, 17(2)
Giannini, E.G., Testa, R. and Savarino, V. (2005). Liver Enzyme Alteration: A Guide for Clinicians. Canadian Medical Association Journal, 172, 367-379. https://doi.org/10.1503/cmaj.1040752
Ginsberg, H.N.(1996). Diabetic dyslipidemia: basic mechanism underlying the common hypertriglyceridemia and low HDL cholesterol levels. Diabetes, 645(suppl 3), S27 –S30
Hammerman, C., Goldstein, R., Kaplan, M., Eran, M. & Goldschmide, D. (1998) . Bilirubin in the premature: toxic waste or natural defence? Clinical Chemistry, 44(12), 255-2553
Hanigan, M.H. & Frierson Jr., H.F.(1996), Immunohistochemical Detection of Gamma-Glutamyl Transpeptidase in Normal Human Tissue. Journal of Histochemistry & Cytochemistry,44, 1101-11108. https://doi.org/10.1177/44.10.8813074
Hanley, A.J., Williams K., Festa, A., Wagenknecht, L.E., D’Agostino, Jr., R.B., Kempf, J., et al. (2004), Elevations in Marker of Liver Injury and Risk of Type 2 Diabetes—The Insulin Resistance. Atherosclerosis Study. Diabetes, 53, 2623-2632. https://doi.org/10.2337/diabetes.53.10.2623
Hopkins, P.N., Wu, L.L., Hunt, S.G. & Jame B.G. (1996). Higher serum bilirubin is associated with decreased risk for early familiar coronary artery disease. Arteriosclerosis Thrombosis Vascular Biology, 16, 250-255.
Hsueh, W.A. & Quinones, M.J. (2003). Role of endothelial dysfunction in insulin resistance. American Journal Cardiology, 92,10–17
Inogochi, T., Sasaki, S., Kobayashi, K. & Takayanagi, R. (2007). Relationship between Gilbert syndrome and prevalence of vascular complications in patients with diabetes. JAMA, 298, 1398-1400
Kern, W.H., Herger, A. H., Payne, J. H. & Dewind, L.T. (1973). Fatty metamorphosis of liver in morbid obesity. Archives of Pathology and Laboratory Medicine, 96, 342–346
Lee, D. H., Ha, M. H., Kim, J. H. & Christiani, D. C. (2003). Gamma-glutamyl Transferases and diabetes: A 4 years follow up study. Diabetologia, 46, 359–364
Lee, D.H. & Jacobs Jr., D.R. (2004). Association between Serum Gamma-Glutamyl transferase and C-Reactive Protein. Atherosclerosis, 178, 327-330. https://doi.org/10.1016/j.atherosclerosis.2004.08.027
Lin, J.P., Donell, C.J., schwager, J.P. & Cupples, L.A. (2006). Association between the UGT1A1 28 allele, bilirubin levels, and coronary heart disease in the Framingham Heart study. Circulation, 114(14), 1476-1481.
Malnick, S.D., Bzergabe., M. & Knobler, H. (2003). Non–alcoholic fatly liver: a common manifestation of a metabolic disorder. Quarterly Journal of Medicine, 96, 699–709
Marchesini, G., Brizi, M., Blanchi, G. & Tomassetti, S. (2001). Nonalcoholic fatty liver disease a feature of the metabolic syndrome. Diabetes, 50, 1844–1850
Martin, A.C. (2006). Cardrovascular risk factors. In a textbook of clinical chemistry and metabolic medicine (7th ed) publisher. Hodder Arnold. pp. 322
Monami,M., Barchini,G.,Lamma,K.& Pala, L. (2008). Liver enzymes and risks of diabetes and cardiovascular disease. Metabolism, 57(3), 387-392
Ndisang, J.F., Lane, N. and Jadhav A. (2009). Upregulation of the haeme oxygenase system ameliorates postprandial and fasting hyperglycaemia in type 2 diabetes. Ameican Journal of Physiology- Endocrinology and Metabolism, 296(3), E1029–104.
Perlstein, T.S., Pande, R.L., Beckman, J.A. & Creager, M.A. (2008). Serum total bilirubin level and prevalent lower – extremity peripheral arterial disease: National Health and Nutrition Examination Survey (NHANES) 1999 – 2004. Arteriosclerosis Thrombosis vascular Biology, 28(1), 166
Schielman, J.D., Goodman , S.I., Mace, J.W.& Patrick, A. (1975). Glutathionuria inborn error of metabolism due to tissue deficiency of gamma – glutamyl transpeptidase. Biochemical and Biophysical Research Communication, 65(1), 68–74. Doi:10.1016/S0006 – 291 (75) 80062
Schwertner, H.A., Jackson, W.G. & Tolan, G. (1994). Association of low serum concentration of bilirubin with increased risk of coronary artery disease. Clinical Chemistry, 40, 18-23.
Sherlock,S. (1985). Diseases of liver and biliary tract. Published by Blackwell Scientific Publication. Pp. 386-387
Stocker, R., Yamamoto, Y., McDonagh, A.F. & Glazer, A.N. (1987). Bilirubin is an antioxidant of possible physiological importance. Science, 235,1043-6
Turgut, O. & Tandogan, I. (2011). Gamma-Glutamyltransferase to determine Cardiovascular Risk: Shifting the Paradigm Forward. Journal of Atherosclerosis and Thrombosis, 18, 177-181
Wang, Y., Koh, W., Yuan, J. & Pan, A. (2016). Association between Liver Enzymes and Incident Type 2 Diabetes in Singapore Chinese Men and Women. British Medical Journal Open Diabetes Research and Care, 4, e000296. https://doi.org/10.1136/bmjdrc-2016-000296
Whitfield, J.B. (2001). Gamma–glutamyl transferase. Critical Review Clinical laboratory science, 38, 263–355
World Health Organization. (1999). Definition, Diagnosis and Classification of Diabetes Mellitus and Its Complications: Report of a WHO Consultation. Part 1, Diagnosis and Classification of Diabetes Mellitus. World Health Organization, Geneva, https://apps.who.int/iris/handle/10665/66040
Zimmerman, H. J., MacMurray, F. G., Rapaport, H. & Alpert, L. K. (1950). Studies of liver in diabetes mellitus. structural and functional abnormalities. Journal of Laboratory and clinical medicine, 36, 912–921
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2021-12-31
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Oyakhire, F., M.A, E., Ogie, E., & Valentine, E. E. (2021). Effect of Diabetes Mellitus on the Excretory Function of the Liver. Medical Laboratory Technology Journal, 7(2), 155–163. https://doi.org/10.31964/mltj.v0i0.416
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