A CLINICAL STUDY OF ORAL GLUCOSE TOLERANCE TEST IN CHRONIC LIVER DISEASE

Abhilash Tadiboina and Kandula Venkateswara Reddy Katuri Medical College. ...................................................................................................................... Manuscript Info Abstract ......................... ........................................................................ Manuscript History Received: 12 September 2019 Final Accepted: 14 October 2019 Published: November 2019 Background: as liver is the principal organ for metabolism of the carbohydrates, chronic liver disease (CLD) may affect carbohydrate metabolism. Hence we can utilise oral glucose tolerance test (OGTT) to study the disturbances in carbohydrate metabolism in CLD. Objectives include: 1) To know clinical features and laboratory manifestations of chronic liver disease. 2) To know various results of OGTT in CLD. 3) To study various classes of cirrhosis (as in child-grading) Methods: Study was conducted over a period of 18 months in Katuri medical college where clinical, laboratory manifestations and OGTT results in 30 cases of CLD and 30 controls (age and sex matched) with cured respiratory tract infection. Age more than 65 years, pregnant women, patients with h/o diabetes, clinical features suggestive of chronic cholestatic diseases and h/o alcoholism in controls were excluded from the present study. Results: CLD was found to be more common in males (73.3%) than females. CLD was more common in lower socioeconomic status (63%). Male: female ratio is equal for chronic hepatitis C equals to one. Alcoholic cirrhosis, chronic alcohol hepatitis and primary hepatoma with cirrhosis were seen only in male and cryptogenic cirrhosis was seen in only female. Most of the cases had anemia. Cirrhosis is the most common cause for CLD (66.6%/20 cases). OGTT showed rise in blood sugar levels in cases which was significant when compared with control group (p<0.05). OGTT showed impaired response in 46.6% cases, impaired glucose tolerance (IGT) in 23.3%, diabetic response in 23.3% and normal response in 53.3% cases. Cirrhosis is the most common (78.5%) cause for impaired glucose response. Conclusions: It can be concluded that CLD is more common in male and lower socioeconomic status. There is significant impaired response to glucose load in CLD. Cirrhosis, among CLD’s is the most common etiology for impaired response.

1. In view of the central role 1 the liver plays in blood glucose regulation, it is not surprising that abnormalities of carbohydrate metabolism are found in CLD, like cirrhosis of liver, chronic hepatitis, hepatocellular carcinoma, etc. 2. Metabolic disorders are evident in patients with advanced liver disease, and the manifestations are similar regardless of the initial etiologic insult 2 . To a varying degree, similar abnormalities are observed in patients with severe chronic hepatitis, micronodular cirrhosis, and post necrotic cirrhosis. 3. The liver maintains a healthy level of blood sugar by a combination of gluconeogenesis, glycogenolysis, and glycogenesis. The metabolic changes in cirrhosis are complex and not fully understood. In fulminant acute hepatic necrosis the blood glucose levels may be low; this is rare in chronic liver disease. 4. In fasted patients with cirrhosis, the contributions of carbohydrates to energy production are reduced to (2% Vs. 38% in control) with contributions from fat increasing (86% Vs 45% in control) 3 . This may be caused by impaired release of hepatic glucose or a reduced reserve of glycogen in the liver. 5. However, in cirrhotics, fallowing a meal 4 or glucose load, there is hyperglycemia because of inability of liver to metabolize glucose, probably due to insulin resistance. Patients with cirrhosis may have elevated serum lactate levels, reflecting the decreased capacity of liver to utilize lactate for gluconeogenesis. 6. It has been shown experimentally that hepatectomised 5 dog rapidly developed hypoglycemia unless glucose is maintained with intravenous glucose drip; this can be explained by the fact that G-6-Pase is present mainly in the liver.
Advanced genetic hemochromatosis causes diabetes mellitus; Diabetes is also associated with chronic hepatitis C virus infection 6,7 and may occur in patients with chronic autoimmune hepatitis, probably due to shared immune genetic predisposition (HLA-B8 & HLA-DR3).
Disturbances of carbohydrate metabolism in chronic liver disease were directly correlated with degree of hepatocellular dysfunction 8 . The underlying mechanisms of these are sophisticated and not fully understood 8,9 . Oral glucose tolerance test (OGTT) can be used for assessing the glucose homeostatic power of the liver in chronic liver disease, where the reserve function reduced as there are many factors that alter the glucose tolerance curves, for example infections, old age, drugs, and many other systemic diseases. Hence other evidence like previous history of diabetes mellitus, history of taking diuretics and other causes of glucose intolerance should be excluded before interpreting the glucose tolerance test.
Study of OGTT is superior 10 to intravenous GTT because glucose is presented to the body by a natural route and there is an opportunity for regular stimulation of insulin secretion by various hormones of gastrointestinal tract. Many studies with intravenous GTT have shown abnormal glucose tolerance curve in a significant proportion of cases. Objectives:-

Inclusion and exclusion criteria: Inclusion criteria:
Patients were presenting to our hospital with clinical and /or histopathologically diagnosed chronic liver disease between the age group 18-65 years.     Anorexia was the most common (80%) symptom of CLD, seen in 24 cases.
Fatigue is the next common (70%) symptom seen in 21 cases. Distention of abdomen, nausea and vomiting, jaundice, and pain abdomen are also frequent, seen in 36.6%, 33.3%, 33.3%, and 33.3%, respectively. Fever and body ache is seen in 30% each.
Hematemesis/ melena was least common (16.6%) symptom seen in severe cases of cirrhosis (83.3% of Child-Pugh's Class-B).  There was a history of previous blood transfusion, history of similar complaints in childhood, extramarital sex in 2 (6.6%) persons each. There is past history of needle prick injury in one case and history of similar complaints in husband in one case.
History of similar complaints is one year, in case of alcoholic hepatitis and 14 years in chronic persistent hepatitis with childhood history, the average being 5.8 years.
Average Body mass index (BMI) is 18.6kg/m 2; male has lower (compared to a minimum of 20 kg/m 2 ) BMI (59.09% are malnourished), compared to females (normal is minimum of 18kg/m 2 ) in whom 35.7% have lower BMI. Ascites is the most common (53.3%) sign seen in 16 cases.
Hepatomegaly is the next common sign seen in 50% of cases.

Mean serum alkaline phosphatase in IU/L is 50, with being lowest being
The highest is 156, seen in primary hepatom a with cirrhosis.
Cases including a case of hepatoma have high values and severe cirrhosis (86.6% are class B Child-Pugh's grading), and one example (14.4%) was chronic hepatitis.
Mean hemoglobulin is 9.97 gm% with 7.8 and 12.8 lowest and highest, respectively; low values are seen in severe cirrhosis and hepatoma. Among cases, 63% of males are anemic (<12gm%), and 50% of females are anemic (<10gm%)Total count, differential count, and platelet count were within normal limits in all cases. Clotting time and bleeding time are within normal limits. In peripheral smear, 66.6 % (20cases) showed normocytic normochromic response rest showed microcytic hypochromic response, because of inadequate intake or chronic blood loss through varices. Serum creatinine was within normal range for all cases, and none of them were in hepato-renal syndrome.
Serum electrolytes levels, including K + are within normal limits. In all patients with clinical ascites, ascitic fluid analysis was done and shown to be transudate. None of the cases had any autoimmune disease or showed any autoantibodies. Analysis for viral markers was done for all cases, HCV Ab is positive in 11 (36.6%)cases, HBs Ag is positive in 7 (23.3%), and no viral markers were found in 12 (40%) cases.      When the etiology of chronic liver disease is considered, of 30 cases, 20 (66.6%) were cirrhosis, and 10 (33.3%)were chronic hepatitis. Out of 20 cases of cirrhosis, 9 (30%) were alcoholic cirrhosis, 9 (30%) were post necrotic cirrhosis, one example was primary hepatoma with cirrhosis and one case of cryptogenic cirrhosis.
Endoscopic examination showed Grade 1 esophageal varices in 3 (10%) cases and Grade 2 esophageal varices in one case. All are severe cases of cirrhosis (Child-Pugh's Class-B).
Cases how have volunteered and gave written consent were subjected to the Oral glucose tolerance test (OGTT). Cases were fed with minimum of 300g of carbohydrate per day for three days prior to OGTT.
Patients with cured respiratory tract infection, after age, sex, and BMI (mean-18.6 kg/m 2 ) matching were taken as controls. Persons who had previous history of jaundice, alcoholism, diabetes and exposure to other hepatotoxic drugs were excluded. Controls were fed with a minimum of 300g of carbohydrate per day for three days prior to OGTT were subjected to OGTT, as for cases. The mean blood glucose level in case and control at fasting, 1/2hr, 1hr, 1½ hr, 2 hr are as follows. After OGTT, data is tabulated and analyzed in both case and control groups. Case and control are compared using 'paired T-test' and calculated the p-value.  When means of case and control are compared, there is a significant difference in 1hr, 1½ hrs, 2-hrs glucose levels, (si.e., p:0001).  OGTT shows impaired response in 14 (46.6%) cases, impaired glucose tolerance (IGT) in 7 (23.3%)cases, diabetic response in 7 (23.3%) and normal response in 16 (53.3%) cases. There was fasting hypoglycemia in a case of cirrhosis with hepatoma.
The diabetic response is seen mainly (2 cases each) seen in the age group 31-40 in males and females. IGT is seen in one case each, in all age groups in males and one each in 41-50 and 61-70 age group in females.