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International Journal of Science and Healthcare Research Vol.4; Issue: 3; July-Sept. 2019 Website: www.ijshr.com Original Research Article ISSN: 2455-7587

Deranged Function Tests in Type 2 Diabetes: A Retrospective Study

Dr Aditi Singh1, Dr Deepika Dalal1, Dr Ashish Kumar Malik2, Dr Anuj Chaudhary3

1Demonstrator, Department of Biochemistry, Pt B D Sharma Post graduate Institute of Medical Sciences. 2Senior Resident, Department of Psychiatry, Pt B D Sharma Post graduate Institute of Medical Sciences. 3Consultant, Jeet hospital, Guhana, Rohtak,

Corresponding Author: Dr Deepika Dalal

ABSTRACT Keywords- Type 2 Diabetes, liver function, alanine aminotransferase, aspartate Background: Liver associated disorders like aminotransferase, , diabetes altered LFTs such as alanine aminotransferase mellitus. (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and gamma- INTRODUCTION glutamyltranspeptidase (GGT) in the , Diabetes mellitus (DM) refers to a fatty , , hepato-cellular group of metabolic disorders characterized carcinoma and are a common by with disturbances in occurrence in type 2 DM. carbohydrate, lipid, and protein Aim and Objective: To assess the association between liver function parameters and type 2 due to absolute or relative deficiency of diabetes (T2D) in a north Indian population. insulin secretion. Type 2 DM is the more Material and Methods: The study was prevalent variety of DM caused by conducted among 133 Type 2 DM patients in resistance to insulin action and inadequate the department of Biochemistry, Pt. B.D Sharma compensatory insulin secretory response. [1] Postgraduate Institute of Medical Sciences, The prevalence of diabetes Rohtak, Haryana, India. Data from type 2 DM worldwide was estimated to be 2.8% in diagnosed patients was retrospectively 2000 and 4.4% in 2030 and it has been reviewed. Reports of outpatient fasting serum found to be more prevalent in men than and LFTs (which included serum levels women. The total number of diabetes is of total , AST, ALT, ALP, and projected to increase from 171 million in ) were compiled. LFTs were advised to [2] these patients as a part of routine screening. 2000 to 366 million in 2030. Results: It was found that the frequencies of The liver plays a central role in elevated Bil, elevated ALT, elevated AST, maintaining glucose homeostasis. Loss of elevated ALP and diminished albumin were insulin effect on the liver leads to 31.5%, 52.6%,59.3%, 42.1% and 73.6% glycogenolysis and an increase in hepatic respectively in the Type 2 DM cases. Moreover, glucose production. The precise genetic, the concentration of S. ALP correlated environmental, and metabolic factors and significantly with the random serum glucose sequence of events that lead to the levels. The correlation was significantly positive underlying insulin resistance, however, is in the diabetic cases (r = 0.20, P < 0.05). not fully understood. [3] Conclusion: The current study highlights the Liver associated disorders like importance of liver function monitoring in patients with type 2 DM. This report would be altered LFTs such as alanine helpful inencouraging the clinicians to give aminotransferase (ALT), aspartate interest in monitoring this neglected diabetic aminotransferase (AST), alkaline hepatic complication in individuals suffering phosphatase (ALP), and gamma- from type 2 DM. glutamyltranspeptidase (GGT) in the serum, , cirrhosis, hepato-cellular carcinoma and acute liver failure are a

International Journal of Science and Healthcare Research (www.ijshr.com) 27 Vol.4; Issue: 3; July-September 2019 Aditi Singh et.al. Deranged Liver Function Tests in Type 2 Diabetes: A Retrospective Study common occurrence in type 2 DM. [4,5] RESULTS Chronic hyperinsulinemia and relative Table 1: Frequency of normal and abnormal liver function tests in the study sample insulin resistance is associated with Parameter Normal (Total = 133) Abnormal increased lipogenesis and associated fatty Total Bilirubin 91 (69.5%) 42(31.5%) AST 54 (40.7%) 79(59.3%) changes. Moreover, accumulation of free ALT 63 (47.4%) 70(52.6%) is known to be toxic to ALP 77 (57.9%) 56(42.1%) hepatocytes leading to increased oxidative Albumin 32(26.4%) 98(73.6%) stress levels and increase in proinflammatory cytokine – Tissue Necrotic Table 1 shows the normal and abnormal Factor. [6] LFT values in the total 133 cases. The table shows that the frequencies of elevated Bil, MATERIALS AND METHOD elevated ALT, elevated AST, elevated ALP The study was conducted among 133 and diminished albumin were 31.5%, Type 2 DM patients in the department of 52.6%, 59.3%, 42.1% and 73.6% Biochemistry, Pt. B.D Sharma Postgraduate respectively. Institute of Medical Sciences, Rohtak, The most common abnormality in liver Haryana, India. function test was the decreased values of Data from type 2 DM diagnosed S.albumin, in 98 patients (73.6%) whereas, patients was retrospectively reviewed. elevated T.Bil in 42 patients(31.5%) was the Reports of outpatient fasting serum glucose least common abnormality observed. and LFTs (which included serum levels of Table 2: Mean values of liver function tests in the study cases total bilirubin, AST, ALT, ALP, and Parameter Mean±SD albumin) were compiled. LFTs were Total Bilirubin 1.05±1.38 AST 123.42±227.46 advised to these patients as a part of routine ALT 130.85±263.32 screening. ALP 144.20±84.22 The LFTs were estimated in auto- Albumin 3.09±1.06 analyzer (RandoxSuzuka, United Kingdom, Table 2 shows that the mean value of all the model no. 6L7WD5J) using kits provided parameters of liver function test was by Randox laboratories .Quality control was deranged in the all the diabetic cases. It was done to ensure the validity of the test results found that the mean value of T.Bil,S ALT, using third party control materials (Randox, S. AST, S. ALP and S. Albumin were UK and Christian Medical College, 1.05±1.38, 123.42±227.46, 130.85±263.32, Vellore). The normal reference ranges used 144.20±84.22, 3.09±1.06 respectively. for this study were as follows: Total bilirubin: 0.3–1 mg/dL, ALT: 0–35 U/L, Table 3: Correlation analysis between random serum glucose AST: 0–35 U/L, ALP: 30–120 U/L, and and liver function tests [7] Parameter Correlation coefficient P value albumin: 3.5–5.5 g/dL. The serum levels ( "r") value of total bilirubin, AST, ALT, and ALP were Total Bilirubin 0.017001 0.846 considered deranged when they were more ALT 0.106901 0.221 AST 0.121486 0.164 than the respective reference ranges while ALP 0.202 0.002 the levels of albumin were considered Albumin -0.21 0.812 deranged when they were less than the . For categorization of type 2 Table 3 shows the correlation of random DM from total population, the type 2 DM blood glucose with T.Bil, S.ALT, S.AST, diagnostic criteria provided by the IDF was S.ALP and S.Albumin. It was observed that used. [8] the concentrations of S. ALP correlated Statistical Analysis: Appropriate statistical significantly with the random serum glucose analysis was done using SPSS. Graphs were levels. The correlation was significantly prepared using Excel 2010. positive in the diabetic cases (r = 0.20, P < 0.05). For the other components of LFTs,

International Journal of Science and Healthcare Research (www.ijshr.com) 28 Vol.4; Issue: 3; July-September 2019 Aditi Singh et.al. Deranged Liver Function Tests in Type 2 Diabetes: A Retrospective Study none of the correlations were statistically ALT and AST in 10.4% and 3.3% of type 2 significant (P > 0.05). It was found that the diabetes patients respectively was correlation was not statistically significant demonstrated. [10] Similarly, Studies with the other parameters of LFT (p>0.05). conducted by Bora et al [11] in India and Balogun et al. in Nigeria [12] reported a high prevalence of deranged LFTs of about 71.2% and 70% respectively among the diabetic population. Ghimire et al observed increased level of ALT (57%) and AST (46%) among patients with diabetes mellitus. Moreover, a significant level of elevation in AST and ALT was observed among the patients with DM compared to non-diabetic controls (p<0.05). [13] Wang et al found that higher levels of ALT and GGT were significantly associated with increased risk of T2D (p for trend <0.001 for ALT, p for trend=0.03 for GGT), and the ORs (95%

Figure 1: Correlation analysis between random serum glucose CIs) comparing highest versus lowest and liver function tests tertiles of ALT and GGT were 2.00 (1.01 to 3.96) and 2.38 (1.21 to 4.66), respectively. DISCUSSION A null association was observed for AST, The mean value of all the parameters ALP, and LDH with T2D risk. Adding GGT of liver function test was deranged in the all (<23 vs≥23 IU/L) or ALT (<21 vs≥21 IU/L) the type 2 DM cases. It was found that the to a prediction model resulted in significant mean value of T.Bil, S. ALT, S. AST, S. gain in net reclassification improvement and ALP and S. Albumin were 1.05±1.38, integrated discrimination improvement of 123.42±227.46, 130.85±263.32, 144.20± T2D prediction (all p<0.001). [14] 84.22, 3.09±1.06 respectively. Moreover, a Abnormal liver function tests in very high prevalence of abnormal LFTs was diabetes patients can be attributed to several observed in patients with type 2 DM. factors. Firstly, Hyperinsulinemia might S.albumin was the most commonly affected directly lead to hepatic insulin resistance liver function test in 98 patients (73.6%) with associated fatty changes. This whereas, elevated T.Bil in 42 patients enhanced accumulation in liver is known (31.5%) was the least common abnormality to be directly toxic to hepatocytes, leading observed. Also, the S. ALP levels correlated to increase in and diminished significantly with the random serum glucose synthetic capacity of liver. [15] Secondly, The levels. The correlation was significantly insulin-resistant state is also characterized positive in the type2 DM cases (r = 0.20, P by an increase in pro-inflammatory < 0.05). cytokines such as tumor necrosis factor In support of our findings, Salmela (TNF), which may also contribute to et al studied the liver function tests of 175 hepatocellular injury. [16] Moreover, One of diabetic patients without chronic liver the hepatic manifestation of diabetes disease, where 57% were found to have at mellitus with is least one abnormal LFT and 27% had at NAFLD and more specifically ALT has least two abnormal LFTs. However, these been used as a marker of NAFLD. [17] increases in liver function values were Recently, studies have revealed the rarely more than two times of the upper [9] association of C virus infection in limit of normal. In another cross sectional diabetes patients causing deranged LFTs. [18] study, which was conducted in Iran, a rise of Though relatively infrequent, therapy

International Journal of Science and Healthcare Research (www.ijshr.com) 29 Vol.4; Issue: 3; July-September 2019 Aditi Singh et.al. Deranged Liver Function Tests in Type 2 Diabetes: A Retrospective Study can also contribute to abnormal liver 6. Agarawal J .Prevalence of elevated hepatic function results. [19] enzymes among north Indian patients with type 2 diabetes mellitus. Santosh University CONCLUSION J Health Sci 2015;1:3-6. This study supports the previous 7. Kratz A, Sluss PM, Januzzi JL Jr., Lewandrowski KB. Appendices: Laboratory studies reporting an association between values of clinical importance. In: Kasper abnormal liver function and type 2 diabetes, [20,21] DL, Fauci AS, Longo DL, Braunwald E, conducted in north Indian population. Hauser SL, Jameson JL, editors. Harrison’s The current study highlights the importance Principles of Internal Medicine. 16th ed. of liver function monitoring in patients with The United States of America: The type 2 DM. This report would be helpful in McGraw-Hill Companies, Inc.; 2005. p. encouraging the clinicians to give interest in A1-7. monitoring this neglected diabetic hepatic 8. Varu DMS, Vegad DAM, Jani DHA, complication in individuals suffering from Savalia DCV, Joshi DVS. A Comparative type 2 DM. Moreover, timely diagnosis and Study of Serum between management of the abnormal liver Premenopausal and Postmenopausal Women. Nat J Integ Res Med 2012;3:43-5. parameters may help to minimize liver 9. Salmela PI, Sotaniemi EA, Niemi M, related morbidity and mortality in diabetic Maentausta O. Liver function tests in population. Future attempts should be diabetic patients. Diabetes Care 1984;7: directed toward unraveling the causes of 248–254. hepatic dysfunction in diabetics and 10. Meybodi M A, Afkhami-Ardekani M, examining the impact that hepatic Rashidi M. Prevalence of Abnormal Serum involvement might have on the glycemic Alanine Aminotransferase Levels in Type 2 status. Further researches are needed to Diabetic Patients in Iran. Pakistan Journal of validate the findings, particularly the Biological Sciences 2008;11:2274-2277. predictive utility of liver enzymes for T2D, 11. Bora K, Borah M, Chutia H, Nath CK, Das and investigate the biological mechanisms D, Ruram AA. Presence of concurrent derangements of liver function tests in type for the associations. 2 diabetes and their relationship with

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International Journal of Science and Healthcare Research (www.ijshr.com) 31 Vol.4; Issue: 3; July-September 2019