Comparative study of assessment of liver function in type II diabetes mellitus with non-diabetic individuals

 

 

Abstract               Background: Liver function test commonly used in clinical laboratory to diagnose various liver disorder like hepatitis, and to monitor the progression of liver disease. In present study we have make an effort to carry out various liver function test in diabetes and non-diabetic individuals and compared result of LFT with each other. We have also try to find cause or reason for to established relationship between liver function and diabetes. Material and Methods: Present study carried out in tertiary care hospital Surat. We have analyzed liver function tests like serum SGOT, SGPT, ALP, total protein, albumin, total and direct bilirubin in diabetic and non-diabetic individuals. These parameters are measured in Erba XL-640 fully auto chemistry analyzer. We have also measured height and weight based on this BMI calculated. Statistical data analysis done by SPSS v16 software. Result and Discussion: In present study we have observed significant (p<0.001 for all) higher level of serum SGOT, SGPT, ALP, total protein, albumin and total bilirubin in diabetic subjects compared to non-diabetic individuals. Serum level of SGOT, SGPT, ALP and total protein was found significant (p<0.01) higher in all subjects categorized by age wise like 35-44 years, 45-54 years, 55-64 years and more or 65 years compared to non-diabetic individuals. Serum level of SGOT, ALP and globulin in BMI group of 25-29.9 kg/m2 significantly higher (p<0.01) in diabetic compared to non-diabetic individuals. Conclusions: Individuals with type II diabetes have a higher incidence of liver function test abnormalities than non-diabetic individuals. The most common abnormality is increased in SGPT. Any diabetic patient found to have a slightly increased of SGPT, or increased of SGPT below 250 U/l for more than six months should have to screen for treatable causes of chronic liver disease, particularly hepatitis B, hepatitis C, and hemochromatosis, and other liver disorder which are found with increased incidence in type II diabetes.

Key Words: SGOT, SGPT, ALP, LFT, BMI and Diabetes mellitus.

 

INTRODUCTION

Liver function tests (LFTs) are commonly used in clinical laboratory check for liver disease, monitor the progression liver disorder, and monitor the effects of any kind of hepatotoxic drugs. Commonly used liver function test include the serum alanine aminotransferases (SGPT), aspartate amino transferees (SGOT), alkaline phosphatase (ALP), total and direct bilirubin, total protein, albumin, globulin and A/G ratio and prothrombin measure the concentration of intracellular hepatic enzymes that have leaked into the circulation and serve as a marker of hepatocyte or liver injury. Alkaline phosphatase (ALP), Gama glutamyl transpeptidase (GGT), and bilirubin act as markers of biliary function and cholestasis. Albumin and prothrombin reflect liver synthetic function. The normal serum level of SGOT and SGPT are below 40 units/l. Increased in level of SGOT and SGPT greater than eight times, it reflect either acute viral hepatitis, ischemic hepatitis, or drug- or toxin-induced liver injury. However some time chronic mild increased in SGOT and SGPT below 250 U/l are commonly found in type II diabetes mellitus ¹. In present study we have make an effort to carry out various liver function test in diabetes and non-diabetic individuals and compared result of LFT with each other. We have also try to find cause or reason for to established relationship between liver function and diabetes. The liver helps in maintaining the normal blood glucose level in the fasting and postprandial states. Loss of insulin effect on the liver leads to glycogen breakdown which lead to increased production of blood glucose level. Person with type II diabetes have a higher incidence of liver function test abnormalities than individuals who do not have diabetes. Slightly increased in SGOT and SGPT often indicate underlying insulin resistance. Other potential explanations for increased in SGOT and SGPT in insulin-resistant states include oxidant stress from reactive lipid peroxidation, peroxisomal beta-oxidation, and recruitment of inflammatory cells. Other theory suggested that in insulin resistant condition increased in level of inflammatory cytokines like tumor necrosis factor alpha which may lead to hepatocellular injury ². The above theories all attribute elevated transaminases to direct hepatocyte injury. It is also hypothesized that elevation in ALT, a gluconeogenic enzyme whose gene transcription is suppressed by insulin, could indicate an impairment in insulin signaling rather than purely hepatocyte injury ³.In present study we have make an effort to compared the result of liver function test like serum SGOT, SGPT, ALP, total protein, total and direct bilirubin between diabetic and non-diabetic subjects. We have also distributed finding in various age and BMI wise.

 

MATERIAL AND METHODS

Study was conducted at tertiary care hospital in Surat, Gujarat, after obtaining necessary ethical clearance from the institutional ethical committee. A total number of 149 diabetics and 149 controls between the age group of 35-65 or above years were included in this study. We have analyzed liver function tests like serum SGOT, SGPT, total and direct bilirubin, total protein, albumin, globulin, A/G ratio and ALP and also analyzed FBS and PPBS by Erba XL-640 fully auto biochemistry analyzer. We have also analyzed HbA1c by HPLC based Bio Rad D10 analyzer. We have also measure anthropological data like height, weight and based on that BMI was calculated in kg/m². Statistical analysis done by using SPSS V16 software. Student’s’ test was used for present study and p value <0.05 was considered statistically significant and p value <0.01 and p<0.001 was considered to be highly statistically significant. We have divided diabetic and non-diabetic subjects based on age group like 35-44 years, 45-54 years, 55-64 years and ≥65 years and also divided based on BMI wise like <23 kg/m², 23-25 kg/m², 25-29.9 kg/m² and ≥30 kg/m².

 

RESULT AND DISCUSSION

Table 1: Age wise distribution of diabetic and non-diabetic individuals.

In age group of 35-44 years, 45-54years, 55-64 years and 65 or more years, 38, 44, 46 and 18 diabetic subjects was there, and 75, 30, 19 and 10 control subjects was there out of total 149 subjects from each category.

 

Table 2: BMI wise distribution of diabetic and non-diabetic individuals.

In BMI group of <23kg/m², 23-24.9 kg/m², 25-29.9 kg/m² and ≥ 30 kg/m², 4, 27, 99 and 19 are diabetic subjects out of total 149 subjects, and 17, 54, 73 and 5 are control subjects out of total 149 subjects.

 

 

Table 3: Comparison of renal function tests between diabetic subjects and non-diabetic individuals

As per above mention table, serum level of SGPT, SGOT, ALP are significantly (p<0.001) higher in diabetic subjects compared to non-diabetic individuals. Serum level of total bilirubin is significantly (p<0.05) higher in diabetic subjects compared to non-diabetic subjects. Serum level of total protein and albumin is found significantly (p<0.001) higher in diabetic subjects compared to non-diabetic individuals.

 

Table 4: Comparison of liver function tests in diabetic and non-diabetic individuals in age group of 35-44 years, 45-54 years, 55-64 years and more or 65 years

Above mention table shows that, serum level of SGOT, SGPT, ALP and total protein higher in every age groups in diabetic subjects compared to non-diabetic individuals. But in case of globulin, total and direct bilirubin this pattern not seen in diabetic subjects.

Table 5: comparison of liver function test between diabetic and non-diabetic individuals in BMI group of <23 kg/m², 23-24.9 kg/m², 25-29.9 kg/m² and ≥30 kg/m².

Above table shows that, serum level of SGOT, ALP and globulin significantly (p<0.01) higher in diabetic compared to non-diabetic individual in BMI group of 25-29.9 kg/m². For other parameters uneven pattern was found between diabetic and non-diabetic individuals.

DISCUSSION

In present study we have analyzed liver function test like serum SGOT, SGPT, ALP, total protein, albumin, globulin and total and direct bilirubin in diabetic and non-diabetic individuals in age groups of 35-44 years, 45-54 years, 55-64 years and more or 65 years (table 4) and in BMI group of <23 kg/m², 23-24.9 kg/m², 25-29.9 kg/m² and more or 30 kg/m² (table 5). We do not have measured Gama glutamyl transpeptidase (GGT). We have observed significantly (p<0.001) higher level of SGOT (40 ± 30 U/l) in diabetic and non-diabetic (30 ± 13U/l) individuals. We have observed significantly (p<0.001) higher level of SGPT (51 ± 42 U/l) in diabetic and non-diabetic (49 ± 23 U/l) individuals. We have observed significantly (p<0.001) higher level of ALP (87 ± 36U/l) in diabetic and non-diabetic (76 ± 21 U/l) individuals (table 3). Person with type II diabetes have a higher incidence of liver function test abnormalities than individuals who do not have diabetes. Slightly increased in SGOT and SGPT often indicate underlying insulin resistance. Other potential explanations for increased in SGOT and SGPT in insulin-resistant states include oxidant stress from reactive lipid peroxidation, peroxisomal beta-oxidation, and recruitment of inflammatory cells. Other theory suggested that in insulin resistant condition increased in level of inflammatory cytokines like tumor necrosis factor alpha which may lead to hepatocellular injury4. The above theories all attribute elevated transaminases to direct hepatocyte injury. It is also hypothesized that elevation in SGPT, a gluconeogenic enzyme whose gene transcription is suppressed by insulin, could indicate an impairment in insulin signaling rather than purely hepatocyte injury ³.Result of our study were similar to study conducted by Ohlson et al.(4)found increased in SGPT in non-diabetic Swedish men to be a risk factor for type II diabetes, which is independent of obesity, plasma glucose, lipid, SGOT, bilirubin concentrations, and family history of diabetes. With similar results, Vozaroza et al ⁵ followed 451 non-diabetic Pima Indians for an average of 6.9 years to determine whether liver enzymes increased could be linked to the development of type II diabetes. Prospectively, increasing SGPT level were associated with a decline in hepatic insulin sensitivity and risk of type II diabetes. The authors concluded that higher SGPT is a risk factor for type II diabetes and indicates a potential role of increased hepatic gluconeogenesis and/or inflammation in the pathogenesis of type II diabetes. Salmela et al⁶ studied the prevalence of abnormal LFTs and their relationship to clinical findings in 175 unselected diabetic outpatients in Finland. 118 patients were classified as having type II diabetes and 57 as having type I diabetes. Of those with type II diabetes, 33 patients used insulin in addition to diet and oral hypoglycemic drugs including sulfonylurea and metformin. None of the patients had known chronic liver disease, and none had clinically significant diabetic nephropathy. HbA1c is averaged 11.2 ± 2.4%. LFTs measured included albumin, total bilirubin, AST, ALT, AP and GGT. 57% of the 175 diabetic outpatients (100 subjects) had at least one abnormal LFT; 27% (48 subjects) had at least two abnormal tests. The type II diabetic patients more frequently had elevated SGPT (22.9 vs. 5.3%) levels than those with type I diabetes. Finding of our study are similar to study conducted by Salmela et al ⁶ On the other hand, patients with type I diabetes more frequently had elevated bilirubin levels (21.1 vs. 10.2%).In a larger study, Erbey et al 7 analyzed 18,825 noninstitutionalized patients within the United States with an oversampling of African Americans and Mexican Americans. Of the total sample, 4.1% had elevated SGPT and 6.7% had type II diabetes. Of those with type II diabetes, the prevalence of elevated SGPT was 7.8%, compared to a 3.8% prevalence in those without diabetes. The prevalence of SGPT elevation greater than three times normal was not significantly different between the non-diabetic and diabetic patients (0.4 vs. 0.7%). Those who were overweight (BMI 25–30 kg/m2) and obese (BMI > 30 kg/m2) were more likely to have elevated SGPT. There was a 10.6% prevalence in obese diabetic patients versus a 6.6% prevalence in obese non-diabetic person. Finding of our study are similar to finding of study conducted by Erbey et al.⁷ We have observed serum level of total protein, albumin and bilirubin significantly (p<0.05) higher (7.24 ± 4.90g/dl), (3.9 ± 0.3g/dl) and (0.8 ± 0.3mg/dl) in diabetic subjects compared to non-diabetic (6.7 ± 0.41g/dl), (3.9 ± 0.2g/dl) and (0.78 ± 0.37mg/dl )individuals respectively. Finding of our study are similar to finding of study conducted by Salmela et al.⁶ We have also measured liver function test in diabetic and non-diabetic individuals in different age groups. We found serum level of SGOT, SGPT, ALP and total protein higher in every age groups in diabetic subjects compared to non-diabetic individuals, similar pattern are found in study conducted by Erbey et al. ⁷ But in case of globulin, total and direct bilirubin this pattern not seen in diabetic subjects. We have also measured liver function test in diabetic and non-diabetic subjects in different BMI groups. We found serum level of SGOT, ALP and globulin significantly (p<0.01) higher in diabetic compared to non-diabetic individual in BMI group of 25-29.9 kg/m² which is similar to study done by Erbey et al.¹¹. For other parameters uneven pattern was found between diabetic and non-diabetic individuals.

 

CONCLUSION

Individuals with type II diabetes have a higher incidence of liver function test abnormalities than non-diabetic individuals. The most common abnormality is increased in SGPT. Any diabetic patient found to have a slightly increased of SGPT, or increased of SGPT below 250 U/l for more than six months should have to screen for treatable causes of chronic liver disease, particularly hepatitis B, hepatitis C, and hemochromatosis, and other liver disorder which are found with increased incidence in type II diabetes. In patients for whom a medical history and physical examination do not raise any kind of suspicion of other causes of increased in liver function tests, such as medications, alcohol, autoimmunity, metabolic etiology, or hereditary etiology, and for those who have no evidence of more serious liver disease, such higher level of bilirubin or prothrombin time or decreases in albumin, further diagnostic workup is probably not required.

 

REFERENCES

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• Ohlson LO, Larsson B, Bjorntorp P, Erksson H, Svardsudd K,Welin L, Tibblin G,Wilhelmsen L: Risk factors for type 2 diabetes mellitus: thirteen and one-half years of follow-up of the participants in a study of Swedish men born in 1913. Diabetologia 31:798–305, 1988.
• Vozarova B, Stefan N, Lindsay RS, Saremi A, Pratley RE, Bogardus C, Tataranni PA: High alanine aminotransferases is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes. Diabetes 51:1889–1895, 2002
• Salmela PI, Sotaniemi EA, Niemi M, Maentausta O: Liver function tests in diabetic patients. Diabetes Care 7:248–254, 1984
• Erbey JR, Silberman C, Lydick E: Prevalence of abnormal serum alanine aminotransferase levels in obese patients and patients with type 2 diabetes. Am J Med 109:588–590, 2000.